https://www.wikidoc.org/api.php?action=feedcontributions&user=Shankar+Kumar&feedformat=atom
wikidoc - User contributions [en]
2024-03-28T23:41:06Z
User contributions
MediaWiki 1.40.0
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1234538
Ixekizumab
2016-06-06T06:49:35Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-[[interleukin 17|interleukin-17]] [[monoclonal antibody]]<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque]] [[psoriasis]] who are candidates for systemic therapy or [[phototherapy]]<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%)<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Moderate to severe [[plaque]] [[psoriasis]]=====<br />
======Dosage======<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
======Tuberculosis Assessment Prior to Initiation of Ixekizumab======<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
======Important Administration Instructions======<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
======Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]======<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions.<br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|useInPregnancyFDA=There are no available data on Ixekizumab use in pregnant women to inform any drug associated risks. Human [[IgG]] is known to cross the placental barrier; therefore, Ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.<br />
<br />
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.<br />
<br />
*Animal Data<br />
<br />
An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by [[subcutaneous injection]] during [[organogenesis]] to near [[parturition]] at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.<br />
<br />
In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly [[subcutaneous]] doses of ixekizumab up to 19 times the MRHD from the beginning of [[organogenesis]] to [[parturition]]. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or [[congenital defect]]. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.<br />
|useInNursing=There are no data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ixekizumab and any potential adverse effects on the breastfed infant from Ixekizumab or from the underlying maternal condition.<br />
|useInPed=The safety and effectiveness of Ixekizumab in pediatric patients (<18 years of age) have not been evaluated.<br />
|useInGeri=Of the 4204 [[psoriasis]] subjects exposed to Ixekizumab, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.<br />
|overdose=In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.<br />
|drugBox={{Drugbox2<br />
| Verifiedfields = changed<br />
| verifiedrevid = 458270595<br />
| type = mab<br />
| image = <br />
| alt = <br />
| mab_type = mab<br />
| source = zu<br />
| target = [[interleukin 17a|IL-17a]]<br />
| tradename = Taltz<br />
| Drugs.com = {{Drugs.com|parent|taltz}}<br />
| MedlinePlus = <br />
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --><br />
| pregnancy_US = <!-- A / B / C / D / X --><br />
| pregnancy_category= <br />
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled --><br />
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --><br />
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM --><br />
| legal_US = Rx-only<br />
| legal_status = <br />
| routes_of_administration = <br />
| bioavailability = <br />
| protein_bound = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
| CAS_number_Ref = {{cascite|changed|??}}<br />
| CAS_number = 1143503-69-8<br />
| ATC_prefix = none<br />
| ATC_suffix = <br />
| PubChem = <br />
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}<br />
| ChemSpiderID = none<br />
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}<br />
| DrugBank =<br />
| C=6492 | H=10012 | N=1728 | O=2028 | S=46<br />
| molecular_weight = 146.2 kg/mol<br />
}}<br />
|mechAction=Ixekizumab is a humanized IgG4 [[monoclonal antibody]] that selectively binds with the [[interleukin 17]]A (IL-17A) [[cytokine]] and inhibits its interaction with the [[interleukin 17|IL-17]] receptor. [[interleukin 17|IL-17A]] is a naturally occurring [[cytokine]] that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory [[cytokine]]s and [[chemokine]]s.<br />
|PD=No formal pharmacodynamic studies have been conducted with Ixekizumab.<br />
|PK=======Absorption======<br />
<br />
Following a single [[subcutaneous]] dose of 160 mg in subjects with [[psoriasis|plaque psoriasis]], ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.<br />
<br />
Steady-state concentrations were achieved by Week 8 following the 160 mg starting dose and 80 mg every 2 weeks dosing regimen; the mean ±SD steady-state trough concentration was 9.3 ±5.3 mcg/mL. Steady-state concentrations were achieved approximately 10 weeks after switching from the 80 mg every 2 weeks dosing regimen to the 80 mg every 4 weeks dosing regimen at Week 12. The mean ±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.<br />
<br />
In studies of subjects with plaque psoriasis, ixekizumab [[bioavailability]] ranged from 60% to 81% following [[subcutaneous]] injection. Administration of ixekizumab via injection in the thigh achieved a higher [[bioavailability]] relative to that achieved using other injection sites including the arm and abdomen.<br />
<br />
======Distribution======<br />
<br />
The mean (geometric CV%) [[volume of distribution]] at steady-state was 7.11 L (29%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
======Elimination======<br />
<br />
The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 [[monoclonal antibody]] ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous [[IgG]].<br />
<br />
The mean systemic clearance was 0.39 L/day (37%) and the mean (geometric CV%) [[half life]] was 13 days (40%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
*Weight<br />
<br />
Ixekizumab clearance and [[volume of distribution]] increase as body weight increases.<br />
<br />
*Dose Linearity<br />
Ixekizumab exhibited dose-proportional [[pharmacokinetics]] in subjects with [[psoriasis|plaque psoriasis]] over a dose range from 5 mg (not the recommended dose) to 160 mg following [[subcutaneous]] administration.<br />
|nonClinToxic=======[[Carcinogenesis]], [[Mutagenesis]], Impairment of Fertility======<br />
<br />
Animal studies have not been conducted to evaluate the [[carcinogenesis|carcinogenic]] or [[mutagenesis|mutagenic]] potential of Ixekizumab. Moreover published literature is mixed on potential effects on malignancy risk due to the inhibition of [[interleukin 17|IL-17A]] activity, the pharmacological action of Ixekizumab. Some published literature suggests that [[interleukin 17|IL-17A]] directly promotes cancer cell invasion, suggesting a potential beneficial effect by Ixekizumab, whereas other reports indicate [[interleukin 17|IL-17A]] promotes T-cell mediated tumor rejection, suggesting a potential adverse effect by Ixekizumab. However, neutralization of [[interleukin 17|IL-17A]] with Ixekizumab has not been studied in these models. Depletion of [[interleukin 17|IL-17A]] with a neutralizing [[antibody]] inhibited tumor development in mice, suggesting a potential beneficial effect by Ixekizumab. The relevance of experimental findings in mouse models for [[malignancy]] risk in humans is unknown.<br />
<br />
No effects on [[fertility]] parameters such as reproductive organs, [[menstrual cycle]] length, or [[sperm]] analysis were observed in sexually mature cynomolgus monkeys that were administered ixekizumab for 13 weeks at a [[subcutaneous]] dose of 50 mg/kg/week (19 times the MRHD on a mg/kg basis). The monkeys were not mated to evaluate [[fertility]].<br />
|clinicalStudies=Three multicenter, [[randomized]], [[double blind|double-blind]], [[placebo controlled|placebo-controlled]] [[clinical trial|trials]] (Trials 1, 2, and 3) enrolled a total of 3866 subjects 18 years of age and older with [[psoriasis|plaque psoriasis]] who had a minimum body surface area involvement of 10%, a static Physician Global Assessment (sPGA) score of ≥3 in the overall assessment ([[plaque]] thickness/[[induration]], [[erythema]], and scaling) of [[psoriasis]] on a severity scale of 0 to 5, a [[Psoriasis]] Area and Severity Index (PASI) score ≥12, and who were candidates for [[phototherapy]] or systemic therapy. <br />
<br />
In all three [[clinical trial|trials]], subjects were [[randomized]] to either [[placebo]] or Ixekizumab (80 mg every two weeks [Q2W]) for 12 weeks, following a 160 mg starting dose. In the two active comparator [[clinical trial|trials]] (Trials 2 and 3), subjects were also [[randomized]] to receive U.S. approved [[etanercept]] 50 mg twice weekly for 12 weeks. <br />
<br />
All three [[clinical trial|trials]] assessed the changes from baseline to Week 12 in the two co-primary endpoints: 1) PASI 75, the proportion of subjects who achieved at least a 75% reduction in the PASI composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of [[psoriasis|psoriatic]] changes ([[induration]], [[erythema]] and scaling) within the affected regions, and 2) sPGA of “0” (clear) or “1” (minimal), the proportion of subjects with an sPGA 0 or 1 and at least a 2-point improvement. <br />
<br />
Other evaluated outcomes included the proportion of subjects with an sPGA score of 0 (clear), a reduction of at least 90% in PASI (PASI 90), a reduction of 100% in PASI (PASI 100), and an improvement of itch severity as measured by a reduction of at least 4 points on an 11-point itch Numeric Rating Scale. <br />
<br />
Subjects in all treatment groups had a median baseline PASI score ranging from approximately 17 to 18. Baseline sPGA score was severe or very severe in 51% of subjects in Trial 1, 50% in Trial 2, and 48% in Trial 3. <br />
<br />
Of all subjects, 44% had received prior [[phototherapy]], 49% had received prior conventional systemic therapy, and 26% had received prior [[biologics|biologic therapy]] for the treatment of [[psoriasis]]. Of the subjects who had received prior [[biologics|biologic therapy]], 15% had received at least one [[TNF inhibitor|anti-TNF alpha agent]], and 9% had received an anti-IL 12/IL23. A total of 23% of study subjects had a history of [[psoriatic arthritis]]. <br />
<br />
======Clinical Response at Week 12======<br />
<br />
The results of Trials 1, 2, and 3 are presented in Table 2.<br />
<br />
Examination of age, gender, race, body weight, and previous treatment with a [[biologics|biologic]] did not identify differences in response to Ixekizumab among these subgroups at Week 12.<br />
<br />
Subjects treated with Ixekizumab 80 mg Q2W experienced improvement in [[itch]] severity when compared to placebo at Week 12.<br />
<br />
An integrated analysis of the U.S. sites in the two active comparator studies using U.S. approved [[etanercept]], Ixekizumab demonstrated superiority to U.S. approved [[etanercept]] (50 mg twice weekly) on sPGA and PASI scores during the 12 week treatment period. The respective response rates for Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]] 50 mg twice weekly were: sPGA of 0 or 1 (73% and 27%); PASI 75 (87% and 41%); sPGA of 0 (34% and 5%); PASI 90 (64% and 18%), and PASI 100 (34% and 4%).<br />
<br />
======Maintenance and Durability of Response======<br />
<br />
To evaluate the maintenance and durability of response, subjects originally [[randomized]] to Ixekizumab and who were responders at Week 12 (i.e., sPGA of 0 or 1) in Trial 1 and Trial 2 were re-randomized to an additional 48 weeks of either a maintenance dose of Ixekizumab 80 mg Q4W (every four weeks) or [[placebo]]. Non-responders (sPGA >1) at Week 12 and subjects who relapsed (sPGA ≥3) during the maintenance period were placed on Ixekizumab 80 mg Q4W.<br />
<br />
For responders at Week 12, the percentage of subjects who maintained this response (sPGA 0 or 1) at Week 60 (48 weeks following re-[[randomization]]) in the integrated [[clinical trial|trials]] (Trial 1 and Trial 2) was higher for subjects treated with Ixekizumab 80 mg Q4W (75%) compared to those treated with [[placebo]] (7%).<br />
<br />
For responders at Week 12 who were re-[[randomized]] to treatment withdrawal (i.e., [[placebo]]), the median time to relapse (sPGA ≥3) was 164 days in the integrated [[clinical trial|trials]]. Among these subjects, 66% regained a response of at least 0 or 1 on the sPGA within 12 weeks of restarting treatment with Ixekizumab 80 mg Q4W.<br />
|howSupplied=Ixekizumab injection is a sterile, [[preservative]] free, clear and colorless to slightly yellow solution available in a single-dose prefilled [[autoinjector]] or a single-dose prefilled [[syringe]] to deliver 80 mg ixekizumab.<br />
<br />
Ixekizumab is supplied as:<br />
|storage=Ixekizumab is sterile and preservative-free. Discard any unused portion.<br />
<br />
*Ixekizumab must be protected from light until use.<br />
*Store refrigerated at 2°C to 8°C (36°F to 46°F).<br />
*Do not freeze. Do not use Ixekizumab if it has been frozen.<br />
*Do not shake.<br />
*Discard the Ixekizumab single-dose [[autoinjector]] or [[syringe]] after use in a puncture-resistant container.<br />
*Not made with natural rubber latex.<br />
|fdaPatientInfo=Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use) before the patient starts using Ixekizumab, and each time the prescription is renewed, as there may be new information they need to know.<br />
<br />
*Instructions on Self-Administration: Provide guidance to patients and caregivers on proper [[subcutaneous]] injection technique, including [[aseptic]] technique, and how to use the [[autoinjector]] or prefilled [[syringe]] correctly.<br />
<br />
*Infection: Inform patients that Ixekizumab may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to the healthcare provider, and contacting their healthcare provider if they develop any symptoms of infection.<br />
<br />
*Allergic Reactions: Advise patients to seek immediate medical attention if they experience any symptoms of serious [[hypersensitivity]] reactions.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1234537
Ixekizumab
2016-06-06T04:18:29Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-[[interleukin 17|interleukin-17]] [[monoclonal antibody]]<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque]] [[psoriasis]] who are candidates for systemic therapy or [[phototherapy]]<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%)<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Moderate to severe [[plaque]] [[psoriasis]]=====<br />
======Dosage======<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
======Tuberculosis Assessment Prior to Initiation of Ixekizumab======<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
======Important Administration Instructions======<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
======Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]======<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions.<br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|useInPregnancyFDA=There are no available data on Ixekizumab use in pregnant women to inform any drug associated risks. Human [[IgG]] is known to cross the placental barrier; therefore, Ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.<br />
<br />
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.<br />
<br />
*Animal Data<br />
<br />
An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by [[subcutaneous injection]] during [[organogenesis]] to near [[parturition]] at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.<br />
<br />
In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly [[subcutaneous]] doses of ixekizumab up to 19 times the MRHD from the beginning of [[organogenesis]] to [[parturition]]. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or [[congenital defect]]. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.<br />
|useInNursing=There are no data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ixekizumab and any potential adverse effects on the breastfed infant from Ixekizumab or from the underlying maternal condition.<br />
|useInPed=The safety and effectiveness of Ixekizumab in pediatric patients (<18 years of age) have not been evaluated.<br />
|useInGeri=Of the 4204 [[psoriasis]] subjects exposed to Ixekizumab, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.<br />
|overdose=In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.<br />
|drugBox={{Drugbox2<br />
| Verifiedfields = changed<br />
| verifiedrevid = 458270595<br />
| type = mab<br />
| image = <br />
| alt = <br />
| mab_type = mab<br />
| source = zu<br />
| target = [[interleukin 17a|IL-17a]]<br />
| tradename = Taltz<br />
| Drugs.com = {{Drugs.com|parent|taltz}}<br />
| MedlinePlus = <br />
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --><br />
| pregnancy_US = <!-- A / B / C / D / X --><br />
| pregnancy_category= <br />
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled --><br />
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --><br />
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM --><br />
| legal_US = Rx-only<br />
| legal_status = <br />
| routes_of_administration = <br />
| bioavailability = <br />
| protein_bound = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
| CAS_number_Ref = {{cascite|changed|??}}<br />
| CAS_number = 1143503-69-8<br />
| ATC_prefix = none<br />
| ATC_suffix = <br />
| PubChem = <br />
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}<br />
| ChemSpiderID = none<br />
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}<br />
| DrugBank =<br />
| C=6492 | H=10012 | N=1728 | O=2028 | S=46<br />
| molecular_weight = 146.2 kg/mol<br />
}}<br />
<br />
'''Ixekizumab''' is a humanized monoclonal antibody for the treatment of autoimmune diseases.<ref>{{cite web|title=Statement On A Nonproprietary Name Adopted By The USAN Council: Ixekizumab|publisher=[[American Medical Association]]|url=http://www.ama-assn.org/resources/doc/usan/ixekizumab.pdf}}</ref> It was approved by the FDA on 22 March 2016 for the treatment of [[plaque psoriasis]], under the trade name '''Taltz''',<ref>{{cite web|title=FDA approves new psiorasis drug Taltz|publisher=[[Food and Drug Administration]]|url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm491872.htm}}</ref> and by the [[European Medicines Agency]] on 25 April 2016 under the same trade name.<ref>{{cite journal|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/003943/WC500205807.pdf|title=Taltz – EPAR summary for the public|publisher=[[European Medicines Agency]]|date=April 2016}}</ref> Clinical trials included a [[Phase II clinical trial]] of patients with moderate to severe psoriasis,<ref name="pharmazeutische-zeitung">{{cite journal|url=http://pharmazeutische-zeitung.de/index.php?id=41582|journal=Pharmazeutische Zeitung|title=Neue Antikörper in der Pipeline|year=2012|issue=12|language=German}}</ref> and a Phase III [[open-label trial]] {{as of|2013|11|lc=on}}.<ref>{{ClinicalTrialsGov|NCT01624233|A Study in Japanese Participants With Moderate-to-Severe Psoriasis}}</ref><br />
<br />
Ixekizumab was developed by [[Eli Lilly and Company|Eli Lilly and Co.]]<br />
<br />
== Mechanism of action ==<br />
Ixekizumab binds to [[interleukin 17]] and blocks its action. This mechanism is similar to that of another anti-psoriasis antibody, [[brodalumab]], which binds to the [[interleukin-17 receptor]].<ref name="pharmazeutische-zeitung" /><br />
<br />
== References ==<br />
<references/><br />
<br />
{{Monoclonals for immune system}}<br />
{{Interleukin receptor modulators}}<br />
<br />
[[Category:Eli Lilly and Company]]<br />
<br />
<br />
{{monoclonal-antibody-stub}}<br />
{{antineoplastic-drug-stub}}<br />
|mechAction=Ixekizumab is a humanized IgG4 [[monoclonal antibody]] that selectively binds with the [[interleukin 17]]A (IL-17A) [[cytokine]] and inhibits its interaction with the [[interleukin 17|IL-17]] receptor. [[interleukin 17|IL-17A]] is a naturally occurring [[cytokine]] that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory [[cytokine]]s and [[chemokine]]s.<br />
|PD=No formal pharmacodynamic studies have been conducted with Ixekizumab.<br />
|PK=======Absorption======<br />
<br />
Following a single [[subcutaneous]] dose of 160 mg in subjects with [[psoriasis|plaque psoriasis]], ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.<br />
<br />
Steady-state concentrations were achieved by Week 8 following the 160 mg starting dose and 80 mg every 2 weeks dosing regimen; the mean ±SD steady-state trough concentration was 9.3 ±5.3 mcg/mL. Steady-state concentrations were achieved approximately 10 weeks after switching from the 80 mg every 2 weeks dosing regimen to the 80 mg every 4 weeks dosing regimen at Week 12. The mean ±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.<br />
<br />
In studies of subjects with plaque psoriasis, ixekizumab [[bioavailability]] ranged from 60% to 81% following [[subcutaneous]] injection. Administration of ixekizumab via injection in the thigh achieved a higher [[bioavailability]] relative to that achieved using other injection sites including the arm and abdomen.<br />
<br />
======Distribution======<br />
<br />
The mean (geometric CV%) [[volume of distribution]] at steady-state was 7.11 L (29%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
======Elimination======<br />
<br />
The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 [[monoclonal antibody]] ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous [[IgG]].<br />
<br />
The mean systemic clearance was 0.39 L/day (37%) and the mean (geometric CV%) [[half life]] was 13 days (40%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
*Weight<br />
<br />
Ixekizumab clearance and [[volume of distribution]] increase as body weight increases.<br />
<br />
*Dose Linearity<br />
Ixekizumab exhibited dose-proportional [[pharmacokinetics]] in subjects with [[psoriasis|plaque psoriasis]] over a dose range from 5 mg (not the recommended dose) to 160 mg following [[subcutaneous]] administration.<br />
|nonClinToxic=======[[Carcinogenesis]], [[Mutagenesis]], Impairment of Fertility======<br />
<br />
Animal studies have not been conducted to evaluate the [[carcinogenesis|carcinogenic]] or [[mutagenesis|mutagenic]] potential of Ixekizumab. Moreover published literature is mixed on potential effects on malignancy risk due to the inhibition of [[interleukin 17|IL-17A]] activity, the pharmacological action of Ixekizumab. Some published literature suggests that [[interleukin 17|IL-17A]] directly promotes cancer cell invasion, suggesting a potential beneficial effect by Ixekizumab, whereas other reports indicate [[interleukin 17|IL-17A]] promotes T-cell mediated tumor rejection, suggesting a potential adverse effect by Ixekizumab. However, neutralization of [[interleukin 17|IL-17A]] with Ixekizumab has not been studied in these models. Depletion of [[interleukin 17|IL-17A]] with a neutralizing [[antibody]] inhibited tumor development in mice, suggesting a potential beneficial effect by Ixekizumab. The relevance of experimental findings in mouse models for [[malignancy]] risk in humans is unknown.<br />
<br />
No effects on [[fertility]] parameters such as reproductive organs, [[menstrual cycle]] length, or [[sperm]] analysis were observed in sexually mature cynomolgus monkeys that were administered ixekizumab for 13 weeks at a [[subcutaneous]] dose of 50 mg/kg/week (19 times the MRHD on a mg/kg basis). The monkeys were not mated to evaluate [[fertility]].<br />
|clinicalStudies=Three multicenter, [[randomized]], [[double blind|double-blind]], [[placebo controlled|placebo-controlled]] [[clinical trial|trials]] (Trials 1, 2, and 3) enrolled a total of 3866 subjects 18 years of age and older with [[psoriasis|plaque psoriasis]] who had a minimum body surface area involvement of 10%, a static Physician Global Assessment (sPGA) score of ≥3 in the overall assessment ([[plaque]] thickness/[[induration]], [[erythema]], and scaling) of [[psoriasis]] on a severity scale of 0 to 5, a [[Psoriasis]] Area and Severity Index (PASI) score ≥12, and who were candidates for [[phototherapy]] or systemic therapy. <br />
<br />
In all three [[clinical trial|trials]], subjects were [[randomized]] to either [[placebo]] or Ixekizumab (80 mg every two weeks [Q2W]) for 12 weeks, following a 160 mg starting dose. In the two active comparator [[clinical trial|trials]] (Trials 2 and 3), subjects were also [[randomized]] to receive U.S. approved [[etanercept]] 50 mg twice weekly for 12 weeks. <br />
<br />
All three [[clinical trial|trials]] assessed the changes from baseline to Week 12 in the two co-primary endpoints: 1) PASI 75, the proportion of subjects who achieved at least a 75% reduction in the PASI composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of [[psoriasis|psoriatic]] changes ([[induration]], [[erythema]] and scaling) within the affected regions, and 2) sPGA of “0” (clear) or “1” (minimal), the proportion of subjects with an sPGA 0 or 1 and at least a 2-point improvement. <br />
<br />
Other evaluated outcomes included the proportion of subjects with an sPGA score of 0 (clear), a reduction of at least 90% in PASI (PASI 90), a reduction of 100% in PASI (PASI 100), and an improvement of itch severity as measured by a reduction of at least 4 points on an 11-point itch Numeric Rating Scale. <br />
<br />
Subjects in all treatment groups had a median baseline PASI score ranging from approximately 17 to 18. Baseline sPGA score was severe or very severe in 51% of subjects in Trial 1, 50% in Trial 2, and 48% in Trial 3. <br />
<br />
Of all subjects, 44% had received prior [[phototherapy]], 49% had received prior conventional systemic therapy, and 26% had received prior [[biologics|biologic therapy]] for the treatment of [[psoriasis]]. Of the subjects who had received prior [[biologics|biologic therapy]], 15% had received at least one [[TNF inhibitor|anti-TNF alpha agent]], and 9% had received an anti-IL 12/IL23. A total of 23% of study subjects had a history of [[psoriatic arthritis]]. <br />
<br />
======Clinical Response at Week 12======<br />
<br />
The results of Trials 1, 2, and 3 are presented in Table 2.<br />
<br />
Examination of age, gender, race, body weight, and previous treatment with a [[biologics|biologic]] did not identify differences in response to Ixekizumab among these subgroups at Week 12.<br />
<br />
Subjects treated with Ixekizumab 80 mg Q2W experienced improvement in [[itch]] severity when compared to placebo at Week 12.<br />
<br />
An integrated analysis of the U.S. sites in the two active comparator studies using U.S. approved [[etanercept]], Ixekizumab demonstrated superiority to U.S. approved [[etanercept]] (50 mg twice weekly) on sPGA and PASI scores during the 12 week treatment period. The respective response rates for Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]] 50 mg twice weekly were: sPGA of 0 or 1 (73% and 27%); PASI 75 (87% and 41%); sPGA of 0 (34% and 5%); PASI 90 (64% and 18%), and PASI 100 (34% and 4%).<br />
<br />
======Maintenance and Durability of Response======<br />
<br />
To evaluate the maintenance and durability of response, subjects originally [[randomized]] to Ixekizumab and who were responders at Week 12 (i.e., sPGA of 0 or 1) in Trial 1 and Trial 2 were re-randomized to an additional 48 weeks of either a maintenance dose of Ixekizumab 80 mg Q4W (every four weeks) or [[placebo]]. Non-responders (sPGA >1) at Week 12 and subjects who relapsed (sPGA ≥3) during the maintenance period were placed on Ixekizumab 80 mg Q4W.<br />
<br />
For responders at Week 12, the percentage of subjects who maintained this response (sPGA 0 or 1) at Week 60 (48 weeks following re-[[randomization]]) in the integrated [[clinical trial|trials]] (Trial 1 and Trial 2) was higher for subjects treated with Ixekizumab 80 mg Q4W (75%) compared to those treated with [[placebo]] (7%).<br />
<br />
For responders at Week 12 who were re-[[randomized]] to treatment withdrawal (i.e., [[placebo]]), the median time to relapse (sPGA ≥3) was 164 days in the integrated [[clinical trial|trials]]. Among these subjects, 66% regained a response of at least 0 or 1 on the sPGA within 12 weeks of restarting treatment with Ixekizumab 80 mg Q4W.<br />
|howSupplied=Ixekizumab injection is a sterile, [[preservative]] free, clear and colorless to slightly yellow solution available in a single-dose prefilled [[autoinjector]] or a single-dose prefilled [[syringe]] to deliver 80 mg ixekizumab.<br />
<br />
Ixekizumab is supplied as:<br />
|storage=Ixekizumab is sterile and preservative-free. Discard any unused portion.<br />
<br />
*Ixekizumab must be protected from light until use.<br />
*Store refrigerated at 2°C to 8°C (36°F to 46°F).<br />
*Do not freeze. Do not use Ixekizumab if it has been frozen.<br />
*Do not shake.<br />
*Discard the Ixekizumab single-dose [[autoinjector]] or [[syringe]] after use in a puncture-resistant container.<br />
*Not made with natural rubber latex.<br />
|fdaPatientInfo=Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use) before the patient starts using Ixekizumab, and each time the prescription is renewed, as there may be new information they need to know.<br />
<br />
*Instructions on Self-Administration: Provide guidance to patients and caregivers on proper [[subcutaneous]] injection technique, including [[aseptic]] technique, and how to use the [[autoinjector]] or prefilled [[syringe]] correctly.<br />
<br />
*Infection: Inform patients that Ixekizumab may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to the healthcare provider, and contacting their healthcare provider if they develop any symptoms of infection.<br />
<br />
*Allergic Reactions: Advise patients to seek immediate medical attention if they experience any symptoms of serious [[hypersensitivity]] reactions.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233430
Ixekizumab
2016-05-31T06:45:30Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-[[interleukin 17|interleukin-17]] [[monoclonal antibody]]<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque]] [[psoriasis]] who are candidates for systemic therapy or [[phototherapy]]<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%)<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Moderate to severe [[plaque]] [[psoriasis]]=====<br />
======Dosage======<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
======Tuberculosis Assessment Prior to Initiation of Ixekizumab======<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
======Important Administration Instructions======<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
======Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]======<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions.<br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|useInPregnancyFDA=There are no available data on Ixekizumab use in pregnant women to inform any drug associated risks. Human [[IgG]] is known to cross the placental barrier; therefore, Ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.<br />
<br />
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.<br />
<br />
*Animal Data<br />
<br />
An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by [[subcutaneous injection]] during [[organogenesis]] to near [[parturition]] at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.<br />
<br />
In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly [[subcutaneous]] doses of ixekizumab up to 19 times the MRHD from the beginning of [[organogenesis]] to [[parturition]]. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or [[congenital defect]]. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.<br />
|useInNursing=There are no data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ixekizumab and any potential adverse effects on the breastfed infant from Ixekizumab or from the underlying maternal condition.<br />
|useInPed=The safety and effectiveness of Ixekizumab in pediatric patients (<18 years of age) have not been evaluated.<br />
|useInGeri=Of the 4204 [[psoriasis]] subjects exposed to Ixekizumab, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.<br />
|overdose=In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.<br />
|mechAction=Ixekizumab is a humanized IgG4 [[monoclonal antibody]] that selectively binds with the [[interleukin 17]]A (IL-17A) [[cytokine]] and inhibits its interaction with the [[interleukin 17|IL-17]] receptor. [[interleukin 17|IL-17A]] is a naturally occurring [[cytokine]] that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory [[cytokine]]s and [[chemokine]]s.<br />
|PD=No formal pharmacodynamic studies have been conducted with Ixekizumab.<br />
|PK=======Absorption======<br />
<br />
Following a single [[subcutaneous]] dose of 160 mg in subjects with [[psoriasis|plaque psoriasis]], ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.<br />
<br />
Steady-state concentrations were achieved by Week 8 following the 160 mg starting dose and 80 mg every 2 weeks dosing regimen; the mean ±SD steady-state trough concentration was 9.3 ±5.3 mcg/mL. Steady-state concentrations were achieved approximately 10 weeks after switching from the 80 mg every 2 weeks dosing regimen to the 80 mg every 4 weeks dosing regimen at Week 12. The mean ±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.<br />
<br />
In studies of subjects with plaque psoriasis, ixekizumab [[bioavailability]] ranged from 60% to 81% following [[subcutaneous]] injection. Administration of ixekizumab via injection in the thigh achieved a higher [[bioavailability]] relative to that achieved using other injection sites including the arm and abdomen.<br />
<br />
======Distribution======<br />
<br />
The mean (geometric CV%) [[volume of distribution]] at steady-state was 7.11 L (29%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
======Elimination======<br />
<br />
The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 [[monoclonal antibody]] ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous [[IgG]].<br />
<br />
The mean systemic clearance was 0.39 L/day (37%) and the mean (geometric CV%) [[half life]] was 13 days (40%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
*Weight<br />
<br />
Ixekizumab clearance and [[volume of distribution]] increase as body weight increases.<br />
<br />
*Dose Linearity<br />
Ixekizumab exhibited dose-proportional [[pharmacokinetics]] in subjects with [[psoriasis|plaque psoriasis]] over a dose range from 5 mg (not the recommended dose) to 160 mg following [[subcutaneous]] administration.<br />
|nonClinToxic=======[[Carcinogenesis]], [[Mutagenesis]], Impairment of Fertility======<br />
<br />
Animal studies have not been conducted to evaluate the [[carcinogenesis|carcinogenic]] or [[mutagenesis|mutagenic]] potential of Ixekizumab. Moreover published literature is mixed on potential effects on malignancy risk due to the inhibition of [[interleukin 17|IL-17A]] activity, the pharmacological action of Ixekizumab. Some published literature suggests that [[interleukin 17|IL-17A]] directly promotes cancer cell invasion, suggesting a potential beneficial effect by Ixekizumab, whereas other reports indicate [[interleukin 17|IL-17A]] promotes T-cell mediated tumor rejection, suggesting a potential adverse effect by Ixekizumab. However, neutralization of [[interleukin 17|IL-17A]] with Ixekizumab has not been studied in these models. Depletion of [[interleukin 17|IL-17A]] with a neutralizing [[antibody]] inhibited tumor development in mice, suggesting a potential beneficial effect by Ixekizumab. The relevance of experimental findings in mouse models for [[malignancy]] risk in humans is unknown.<br />
<br />
No effects on [[fertility]] parameters such as reproductive organs, [[menstrual cycle]] length, or [[sperm]] analysis were observed in sexually mature cynomolgus monkeys that were administered ixekizumab for 13 weeks at a [[subcutaneous]] dose of 50 mg/kg/week (19 times the MRHD on a mg/kg basis). The monkeys were not mated to evaluate [[fertility]].<br />
|clinicalStudies=Three multicenter, [[randomized]], [[double blind|double-blind]], [[placebo controlled|placebo-controlled]] [[clinical trial|trials]] (Trials 1, 2, and 3) enrolled a total of 3866 subjects 18 years of age and older with [[psoriasis|plaque psoriasis]] who had a minimum body surface area involvement of 10%, a static Physician Global Assessment (sPGA) score of ≥3 in the overall assessment ([[plaque]] thickness/[[induration]], [[erythema]], and scaling) of [[psoriasis]] on a severity scale of 0 to 5, a [[Psoriasis]] Area and Severity Index (PASI) score ≥12, and who were candidates for [[phototherapy]] or systemic therapy. <br />
<br />
In all three [[clinical trial|trials]], subjects were [[randomized]] to either [[placebo]] or Ixekizumab (80 mg every two weeks [Q2W]) for 12 weeks, following a 160 mg starting dose. In the two active comparator [[clinical trial|trials]] (Trials 2 and 3), subjects were also [[randomized]] to receive U.S. approved [[etanercept]] 50 mg twice weekly for 12 weeks. <br />
<br />
All three [[clinical trial|trials]] assessed the changes from baseline to Week 12 in the two co-primary endpoints: 1) PASI 75, the proportion of subjects who achieved at least a 75% reduction in the PASI composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of [[psoriasis|psoriatic]] changes ([[induration]], [[erythema]] and scaling) within the affected regions, and 2) sPGA of “0” (clear) or “1” (minimal), the proportion of subjects with an sPGA 0 or 1 and at least a 2-point improvement. <br />
<br />
Other evaluated outcomes included the proportion of subjects with an sPGA score of 0 (clear), a reduction of at least 90% in PASI (PASI 90), a reduction of 100% in PASI (PASI 100), and an improvement of itch severity as measured by a reduction of at least 4 points on an 11-point itch Numeric Rating Scale. <br />
<br />
Subjects in all treatment groups had a median baseline PASI score ranging from approximately 17 to 18. Baseline sPGA score was severe or very severe in 51% of subjects in Trial 1, 50% in Trial 2, and 48% in Trial 3. <br />
<br />
Of all subjects, 44% had received prior [[phototherapy]], 49% had received prior conventional systemic therapy, and 26% had received prior [[biologics|biologic therapy]] for the treatment of [[psoriasis]]. Of the subjects who had received prior [[biologics|biologic therapy]], 15% had received at least one [[TNF inhibitor|anti-TNF alpha agent]], and 9% had received an anti-IL 12/IL23. A total of 23% of study subjects had a history of [[psoriatic arthritis]]. <br />
<br />
======Clinical Response at Week 12======<br />
<br />
The results of Trials 1, 2, and 3 are presented in Table 2.<br />
<br />
Examination of age, gender, race, body weight, and previous treatment with a [[biologics|biologic]] did not identify differences in response to Ixekizumab among these subgroups at Week 12.<br />
<br />
Subjects treated with Ixekizumab 80 mg Q2W experienced improvement in [[itch]] severity when compared to placebo at Week 12.<br />
<br />
An integrated analysis of the U.S. sites in the two active comparator studies using U.S. approved [[etanercept]], Ixekizumab demonstrated superiority to U.S. approved [[etanercept]] (50 mg twice weekly) on sPGA and PASI scores during the 12 week treatment period. The respective response rates for Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]] 50 mg twice weekly were: sPGA of 0 or 1 (73% and 27%); PASI 75 (87% and 41%); sPGA of 0 (34% and 5%); PASI 90 (64% and 18%), and PASI 100 (34% and 4%).<br />
<br />
======Maintenance and Durability of Response======<br />
<br />
To evaluate the maintenance and durability of response, subjects originally [[randomized]] to Ixekizumab and who were responders at Week 12 (i.e., sPGA of 0 or 1) in Trial 1 and Trial 2 were re-randomized to an additional 48 weeks of either a maintenance dose of Ixekizumab 80 mg Q4W (every four weeks) or [[placebo]]. Non-responders (sPGA >1) at Week 12 and subjects who relapsed (sPGA ≥3) during the maintenance period were placed on Ixekizumab 80 mg Q4W.<br />
<br />
For responders at Week 12, the percentage of subjects who maintained this response (sPGA 0 or 1) at Week 60 (48 weeks following re-[[randomization]]) in the integrated [[clinical trial|trials]] (Trial 1 and Trial 2) was higher for subjects treated with Ixekizumab 80 mg Q4W (75%) compared to those treated with [[placebo]] (7%).<br />
<br />
For responders at Week 12 who were re-[[randomized]] to treatment withdrawal (i.e., [[placebo]]), the median time to relapse (sPGA ≥3) was 164 days in the integrated [[clinical trial|trials]]. Among these subjects, 66% regained a response of at least 0 or 1 on the sPGA within 12 weeks of restarting treatment with Ixekizumab 80 mg Q4W.<br />
|howSupplied=Ixekizumab injection is a sterile, [[preservative]] free, clear and colorless to slightly yellow solution available in a single-dose prefilled [[autoinjector]] or a single-dose prefilled [[syringe]] to deliver 80 mg ixekizumab.<br />
<br />
Ixekizumab is supplied as:<br />
|storage=Ixekizumab is sterile and preservative-free. Discard any unused portion.<br />
<br />
*Ixekizumab must be protected from light until use.<br />
*Store refrigerated at 2°C to 8°C (36°F to 46°F).<br />
*Do not freeze. Do not use Ixekizumab if it has been frozen.<br />
*Do not shake.<br />
*Discard the Ixekizumab single-dose [[autoinjector]] or [[syringe]] after use in a puncture-resistant container.<br />
*Not made with natural rubber latex.<br />
|fdaPatientInfo=Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use) before the patient starts using Ixekizumab, and each time the prescription is renewed, as there may be new information they need to know.<br />
<br />
*Instructions on Self-Administration: Provide guidance to patients and caregivers on proper [[subcutaneous]] injection technique, including [[aseptic]] technique, and how to use the [[autoinjector]] or prefilled [[syringe]] correctly.<br />
<br />
*Infection: Inform patients that Ixekizumab may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to the healthcare provider, and contacting their healthcare provider if they develop any symptoms of infection.<br />
<br />
*Allergic Reactions: Advise patients to seek immediate medical attention if they experience any symptoms of serious [[hypersensitivity]] reactions.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233427
Ixekizumab
2016-05-30T10:26:20Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-[[interleukin 17|interleukin-17]] [[monoclonal antibody]]<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque]] [[psoriasis]] who are candidates for systemic therapy or [[phototherapy]]<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%)<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Moderate to severe [[plaque]] [[psoriasis]]=====<br />
======Dosage======<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
======Tuberculosis Assessment Prior to Initiation of Ixekizumab======<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
======Important Administration Instructions======<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
======Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]======<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions.<br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|useInPregnancyFDA=There are no available data on Ixekizumab use in pregnant women to inform any drug associated risks. Human [[IgG]] is known to cross the placental barrier; therefore, Ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.<br />
<br />
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.<br />
<br />
*Animal Data<br />
<br />
An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by [[subcutaneous injection]] during [[organogenesis]] to near [[parturition]] at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.<br />
<br />
In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly [[subcutaneous]] doses of ixekizumab up to 19 times the MRHD from the beginning of [[organogenesis]] to [[parturition]]. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or [[congenital defect]]. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.<br />
|useInNursing=There are no data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ixekizumab and any potential adverse effects on the breastfed infant from Ixekizumab or from the underlying maternal condition.<br />
|useInPed=The safety and effectiveness of Ixekizumab in pediatric patients (<18 years of age) have not been evaluated.<br />
|useInGeri=Of the 4204 [[psoriasis]] subjects exposed to Ixekizumab, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.<br />
|overdose=In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.<br />
|mechAction=Ixekizumab is a humanized IgG4 [[monoclonal antibody]] that selectively binds with the [[interleukin 17]]A (IL-17A) [[cytokine]] and inhibits its interaction with the [[interleukin 17|IL-17]] receptor. [[interleukin 17|IL-17A]] is a naturally occurring [[cytokine]] that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory [[cytokine]]s and [[chemokine]]s.<br />
|PD=No formal pharmacodynamic studies have been conducted with Ixekizumab.<br />
|PK=======Absorption======<br />
<br />
Following a single [[subcutaneous]] dose of 160 mg in subjects with [[psoriasis|plaque psoriasis]], ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.<br />
<br />
Steady-state concentrations were achieved by Week 8 following the 160 mg starting dose and 80 mg every 2 weeks dosing regimen; the mean ±SD steady-state trough concentration was 9.3 ±5.3 mcg/mL. Steady-state concentrations were achieved approximately 10 weeks after switching from the 80 mg every 2 weeks dosing regimen to the 80 mg every 4 weeks dosing regimen at Week 12. The mean ±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.<br />
<br />
In studies of subjects with plaque psoriasis, ixekizumab [[bioavailability]] ranged from 60% to 81% following [[subcutaneous]] injection. Administration of ixekizumab via injection in the thigh achieved a higher [[bioavailability]] relative to that achieved using other injection sites including the arm and abdomen.<br />
<br />
======Distribution======<br />
<br />
The mean (geometric CV%) [[volume of distribution]] at steady-state was 7.11 L (29%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
======Elimination======<br />
<br />
The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 [[monoclonal antibody]] ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous [[IgG]].<br />
<br />
The mean systemic clearance was 0.39 L/day (37%) and the mean (geometric CV%) [[half life]] was 13 days (40%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
*Weight<br />
<br />
Ixekizumab clearance and [[volume of distribution]] increase as body weight increases.<br />
<br />
*Dose Linearity<br />
Ixekizumab exhibited dose-proportional [[pharmacokinetics]] in subjects with [[psoriasis|plaque psoriasis]] over a dose range from 5 mg (not the recommended dose) to 160 mg following [[subcutaneous]] administration.<br />
|nonClinToxic=======[[Carcinogenesis]], [[Mutagenesis]], Impairment of Fertility======<br />
<br />
Animal studies have not been conducted to evaluate the [[carcinogenesis|carcinogenic]] or [[mutagenesis|mutagenic]] potential of Ixekizumab. Moreover published literature is mixed on potential effects on malignancy risk due to the inhibition of [[interleukin 17|IL-17A]] activity, the pharmacological action of Ixekizumab. Some published literature suggests that [[interleukin 17|IL-17A]] directly promotes cancer cell invasion, suggesting a potential beneficial effect by Ixekizumab, whereas other reports indicate [[interleukin 17|IL-17A]] promotes T-cell mediated tumor rejection, suggesting a potential adverse effect by Ixekizumab. However, neutralization of [[interleukin 17|IL-17A]] with Ixekizumab has not been studied in these models. Depletion of [[interleukin 17|IL-17A]] with a neutralizing [[antibody]] inhibited tumor development in mice, suggesting a potential beneficial effect by Ixekizumab. The relevance of experimental findings in mouse models for [[malignancy]] risk in humans is unknown.<br />
<br />
No effects on [[fertility]] parameters such as reproductive organs, [[menstrual cycle]] length, or [[sperm]] analysis were observed in sexually mature cynomolgus monkeys that were administered ixekizumab for 13 weeks at a [[subcutaneous]] dose of 50 mg/kg/week (19 times the MRHD on a mg/kg basis). The monkeys were not mated to evaluate [[fertility]].<br />
|clinicalStudies=Three multicenter, [[randomized]], [[double blind|double-blind]], [[placebo controlled|placebo-controlled]] [[clinical trial|trials]] (Trials 1, 2, and 3) enrolled a total of 3866 subjects 18 years of age and older with [[psoriasis|plaque psoriasis]] who had a minimum body surface area involvement of 10%, a static Physician Global Assessment (sPGA) score of ≥3 in the overall assessment ([[plaque]] thickness/[[induration]], [[erythema]], and scaling) of [[psoriasis]] on a severity scale of 0 to 5, a [[Psoriasis]] Area and Severity Index (PASI) score ≥12, and who were candidates for [[phototherapy]] or systemic therapy. <br />
<br />
In all three [[clinical trial|trials]], subjects were [[randomized]] to either [[placebo]] or Ixekizumab (80 mg every two weeks [Q2W]) for 12 weeks, following a 160 mg starting dose. In the two active comparator [[clinical trial|trials]] (Trials 2 and 3), subjects were also [[randomized]] to receive U.S. approved [[etanercept]] 50 mg twice weekly for 12 weeks. <br />
<br />
All three [[clinical trial|trials]] assessed the changes from baseline to Week 12 in the two co-primary endpoints: 1) PASI 75, the proportion of subjects who achieved at least a 75% reduction in the PASI composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of [[psoriasis|psoriatic]] changes ([[induration]], [[erythema]] and scaling) within the affected regions, and 2) sPGA of “0” (clear) or “1” (minimal), the proportion of subjects with an sPGA 0 or 1 and at least a 2-point improvement. <br />
<br />
Other evaluated outcomes included the proportion of subjects with an sPGA score of 0 (clear), a reduction of at least 90% in PASI (PASI 90), a reduction of 100% in PASI (PASI 100), and an improvement of itch severity as measured by a reduction of at least 4 points on an 11-point itch Numeric Rating Scale. <br />
<br />
Subjects in all treatment groups had a median baseline PASI score ranging from approximately 17 to 18. Baseline sPGA score was severe or very severe in 51% of subjects in Trial 1, 50% in Trial 2, and 48% in Trial 3. <br />
<br />
Of all subjects, 44% had received prior [[phototherapy]], 49% had received prior conventional systemic therapy, and 26% had received prior [[biologics|biologic therapy]] for the treatment of [[psoriasis]]. Of the subjects who had received prior [[biologics|biologic therapy]], 15% had received at least one [[TNF inhibitor|anti-TNF alpha agent]], and 9% had received an anti-IL 12/IL23. A total of 23% of study subjects had a history of [[psoriatic arthritis]]. <br />
<br />
======Clinical Response at Week 12======<br />
<br />
The results of Trials 1, 2, and 3 are presented in Table 2.<br />
<br />
Examination of age, gender, race, body weight, and previous treatment with a [[biologics|biologic]] did not identify differences in response to Ixekizumab among these subgroups at Week 12.<br />
<br />
Subjects treated with Ixekizumab 80 mg Q2W experienced improvement in [[itch]] severity when compared to placebo at Week 12.<br />
<br />
An integrated analysis of the U.S. sites in the two active comparator studies using U.S. approved [[etanercept]], Ixekizumab demonstrated superiority to U.S. approved [[etanercept]] (50 mg twice weekly) on sPGA and PASI scores during the 12 week treatment period. The respective response rates for Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]] 50 mg twice weekly were: sPGA of 0 or 1 (73% and 27%); PASI 75 (87% and 41%); sPGA of 0 (34% and 5%); PASI 90 (64% and 18%), and PASI 100 (34% and 4%).<br />
<br />
======Maintenance and Durability of Response======<br />
<br />
To evaluate the maintenance and durability of response, subjects originally [[randomized]] to Ixekizumab and who were responders at Week 12 (i.e., sPGA of 0 or 1) in Trial 1 and Trial 2 were re-randomized to an additional 48 weeks of either a maintenance dose of Ixekizumab 80 mg Q4W (every four weeks) or [[placebo]]. Non-responders (sPGA >1) at Week 12 and subjects who relapsed (sPGA ≥3) during the maintenance period were placed on Ixekizumab 80 mg Q4W.<br />
<br />
For responders at Week 12, the percentage of subjects who maintained this response (sPGA 0 or 1) at Week 60 (48 weeks following re-[[randomization]]) in the integrated [[clinical trial|trials]] (Trial 1 and Trial 2) was higher for subjects treated with Ixekizumab 80 mg Q4W (75%) compared to those treated with [[placebo]] (7%).<br />
<br />
For responders at Week 12 who were re-[[randomized]] to treatment withdrawal (i.e., [[placebo]]), the median time to relapse (sPGA ≥3) was 164 days in the integrated [[clinical trial|trials]]. Among these subjects, 66% regained a response of at least 0 or 1 on the sPGA within 12 weeks of restarting treatment with Ixekizumab 80 mg Q4W.<br />
|howSupplied=Ixekizumab injection is a sterile, [[preservative]] free, clear and colorless to slightly yellow solution available in a single-dose prefilled [[autoinjector]] or a single-dose prefilled [[syringe]] to deliver 80 mg ixekizumab.<br />
<br />
Ixekizumab is supplied as:<br />
|storage=Ixekizumab is sterile and preservative-free. Discard any unused portion.<br />
<br />
*Ixekizumab must be protected from light until use.<br />
*Store refrigerated at 2°C to 8°C (36°F to 46°F).<br />
*Do not freeze. Do not use Ixekizumab if it has been frozen.<br />
*Do not shake.<br />
*Discard the Ixekizumab single-dose [[autoinjector]] or [[syringe]] after use in a puncture-resistant container.<br />
*Not made with natural rubber latex.<br />
|fdaPatientInfo=Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use) before the patient starts using TALTZ, and each time the prescription is renewed, as there may be new information they need to know.<br />
<br />
Instructions on Self-Administration: Provide guidance to patients and caregivers on proper subcutaneous injection technique, including aseptic technique, and how to use the autoinjector or prefilled syringe correctly [see Instructions for Use].<br />
<br />
Infection: Inform patients that TALTZ may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to the healthcare provider, and contacting their healthcare provider if they develop any symptoms of infection [see Warnings and Precautions (5.1)].<br />
<br />
Allergic Reactions: Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions (5.3)].<br />
<br />
Eli Lilly and Company, Indianapolis, IN 46285, USA<br />
US License Number 1891<br />
<br />
Product of Ireland<br />
<br />
Copyright © 2016, Eli Lilly and Company. All rights reserved.<br />
<br />
TAL-0001-USPI-20160322<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233426
Ixekizumab
2016-05-30T10:20:33Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-[[interleukin 17|interleukin-17]] [[monoclonal antibody]]<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque]] [[psoriasis]] who are candidates for systemic therapy or [[phototherapy]]<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%)<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Moderate to severe [[plaque]] [[psoriasis]]=====<br />
======Dosage======<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
======Tuberculosis Assessment Prior to Initiation of Ixekizumab======<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
======Important Administration Instructions======<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
======Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]======<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions.<br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|useInPregnancyFDA=There are no available data on Ixekizumab use in pregnant women to inform any drug associated risks. Human [[IgG]] is known to cross the placental barrier; therefore, Ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.<br />
<br />
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.<br />
<br />
*Animal Data<br />
<br />
An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by [[subcutaneous injection]] during [[organogenesis]] to near [[parturition]] at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.<br />
<br />
In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly [[subcutaneous]] doses of ixekizumab up to 19 times the MRHD from the beginning of [[organogenesis]] to [[parturition]]. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or [[congenital defect]]. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.<br />
|useInNursing=There are no data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ixekizumab and any potential adverse effects on the breastfed infant from Ixekizumab or from the underlying maternal condition.<br />
|useInPed=The safety and effectiveness of Ixekizumab in pediatric patients (<18 years of age) have not been evaluated.<br />
|useInGeri=Of the 4204 [[psoriasis]] subjects exposed to Ixekizumab, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.<br />
|overdose=In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.<br />
|mechAction=Ixekizumab is a humanized IgG4 [[monoclonal antibody]] that selectively binds with the [[interleukin 17]]A (IL-17A) [[cytokine]] and inhibits its interaction with the [[interleukin 17|IL-17]] receptor. [[interleukin 17|IL-17A]] is a naturally occurring [[cytokine]] that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory [[cytokine]]s and [[chemokine]]s.<br />
|PD=No formal pharmacodynamic studies have been conducted with Ixekizumab.<br />
|PK=======Absorption======<br />
<br />
Following a single [[subcutaneous]] dose of 160 mg in subjects with [[psoriasis|plaque psoriasis]], ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.<br />
<br />
Steady-state concentrations were achieved by Week 8 following the 160 mg starting dose and 80 mg every 2 weeks dosing regimen; the mean ±SD steady-state trough concentration was 9.3 ±5.3 mcg/mL. Steady-state concentrations were achieved approximately 10 weeks after switching from the 80 mg every 2 weeks dosing regimen to the 80 mg every 4 weeks dosing regimen at Week 12. The mean ±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.<br />
<br />
In studies of subjects with plaque psoriasis, ixekizumab [[bioavailability]] ranged from 60% to 81% following [[subcutaneous]] injection. Administration of ixekizumab via injection in the thigh achieved a higher [[bioavailability]] relative to that achieved using other injection sites including the arm and abdomen.<br />
<br />
======Distribution======<br />
<br />
The mean (geometric CV%) [[volume of distribution]] at steady-state was 7.11 L (29%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
======Elimination======<br />
<br />
The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 [[monoclonal antibody]] ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous [[IgG]].<br />
<br />
The mean systemic clearance was 0.39 L/day (37%) and the mean (geometric CV%) [[half life]] was 13 days (40%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
*Weight<br />
<br />
Ixekizumab clearance and [[volume of distribution]] increase as body weight increases.<br />
<br />
*Dose Linearity<br />
Ixekizumab exhibited dose-proportional [[pharmacokinetics]] in subjects with [[psoriasis|plaque psoriasis]] over a dose range from 5 mg (not the recommended dose) to 160 mg following [[subcutaneous]] administration.<br />
|nonClinToxic=======[[Carcinogenesis]], [[Mutagenesis]], Impairment of Fertility======<br />
<br />
Animal studies have not been conducted to evaluate the [[carcinogenesis|carcinogenic]] or [[mutagenesis|mutagenic]] potential of Ixekizumab. Moreover published literature is mixed on potential effects on malignancy risk due to the inhibition of [[interleukin 17|IL-17A]] activity, the pharmacological action of Ixekizumab. Some published literature suggests that [[interleukin 17|IL-17A]] directly promotes cancer cell invasion, suggesting a potential beneficial effect by Ixekizumab, whereas other reports indicate [[interleukin 17|IL-17A]] promotes T-cell mediated tumor rejection, suggesting a potential adverse effect by Ixekizumab. However, neutralization of [[interleukin 17|IL-17A]] with Ixekizumab has not been studied in these models. Depletion of [[interleukin 17|IL-17A]] with a neutralizing [[antibody]] inhibited tumor development in mice, suggesting a potential beneficial effect by Ixekizumab. The relevance of experimental findings in mouse models for [[malignancy]] risk in humans is unknown.<br />
<br />
No effects on [[fertility]] parameters such as reproductive organs, [[menstrual cycle]] length, or [[sperm]] analysis were observed in sexually mature cynomolgus monkeys that were administered ixekizumab for 13 weeks at a [[subcutaneous]] dose of 50 mg/kg/week (19 times the MRHD on a mg/kg basis). The monkeys were not mated to evaluate [[fertility]].<br />
|clinicalStudies=Three multicenter, [[randomized]], [[double blind|double-blind]], [[placebo controlled|placebo-controlled]] [[clinical trial|trials]] (Trials 1, 2, and 3) enrolled a total of 3866 subjects 18 years of age and older with [[psoriasis|plaque psoriasis]] who had a minimum body surface area involvement of 10%, a static Physician Global Assessment (sPGA) score of ≥3 in the overall assessment ([[plaque]] thickness/[[induration]], [[erythema]], and scaling) of [[psoriasis]] on a severity scale of 0 to 5, a [[Psoriasis]] Area and Severity Index (PASI) score ≥12, and who were candidates for [[phototherapy]] or systemic therapy. <br />
<br />
In all three [[clinical trial|trials]], subjects were [[randomized]] to either [[placebo]] or Ixekizumab (80 mg every two weeks [Q2W]) for 12 weeks, following a 160 mg starting dose. In the two active comparator [[clinical trial|trials]] (Trials 2 and 3), subjects were also [[randomized]] to receive U.S. approved [[etanercept]] 50 mg twice weekly for 12 weeks. <br />
<br />
All three [[clinical trial|trials]] assessed the changes from baseline to Week 12 in the two co-primary endpoints: 1) PASI 75, the proportion of subjects who achieved at least a 75% reduction in the PASI composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of [[psoriasis|psoriatic]] changes ([[induration]], [[erythema]] and scaling) within the affected regions, and 2) sPGA of “0” (clear) or “1” (minimal), the proportion of subjects with an sPGA 0 or 1 and at least a 2-point improvement. <br />
<br />
Other evaluated outcomes included the proportion of subjects with an sPGA score of 0 (clear), a reduction of at least 90% in PASI (PASI 90), a reduction of 100% in PASI (PASI 100), and an improvement of itch severity as measured by a reduction of at least 4 points on an 11-point itch Numeric Rating Scale. <br />
<br />
Subjects in all treatment groups had a median baseline PASI score ranging from approximately 17 to 18. Baseline sPGA score was severe or very severe in 51% of subjects in Trial 1, 50% in Trial 2, and 48% in Trial 3. <br />
<br />
Of all subjects, 44% had received prior [[phototherapy]], 49% had received prior conventional systemic therapy, and 26% had received prior [[biologics|biologic therapy]] for the treatment of [[psoriasis]]. Of the subjects who had received prior [[biologics|biologic therapy]], 15% had received at least one [[TNF inhibitor|anti-TNF alpha agent]], and 9% had received an anti-IL 12/IL23. A total of 23% of study subjects had a history of [[psoriatic arthritis]]. <br />
<br />
======Clinical Response at Week 12======<br />
<br />
The results of Trials 1, 2, and 3 are presented in Table 2.<br />
<br />
Examination of age, gender, race, body weight, and previous treatment with a [[biologics|biologic]] did not identify differences in response to Ixekizumab among these subgroups at Week 12.<br />
<br />
Subjects treated with Ixekizumab 80 mg Q2W experienced improvement in [[itch]] severity when compared to placebo at Week 12.<br />
<br />
An integrated analysis of the U.S. sites in the two active comparator studies using U.S. approved [[etanercept]], Ixekizumab demonstrated superiority to U.S. approved [[etanercept]] (50 mg twice weekly) on sPGA and PASI scores during the 12 week treatment period. The respective response rates for Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]] 50 mg twice weekly were: sPGA of 0 or 1 (73% and 27%); PASI 75 (87% and 41%); sPGA of 0 (34% and 5%); PASI 90 (64% and 18%), and PASI 100 (34% and 4%).<br />
<br />
======Maintenance and Durability of Response======<br />
<br />
To evaluate the maintenance and durability of response, subjects originally [[randomized]] to Ixekizumab and who were responders at Week 12 (i.e., sPGA of 0 or 1) in Trial 1 and Trial 2 were re-randomized to an additional 48 weeks of either a maintenance dose of Ixekizumab 80 mg Q4W (every four weeks) or [[placebo]]. Non-responders (sPGA >1) at Week 12 and subjects who relapsed (sPGA ≥3) during the maintenance period were placed on Ixekizumab 80 mg Q4W.<br />
<br />
For responders at Week 12, the percentage of subjects who maintained this response (sPGA 0 or 1) at Week 60 (48 weeks following re-[[randomization]]) in the integrated [[clinical trial|trials]] (Trial 1 and Trial 2) was higher for subjects treated with Ixekizumab 80 mg Q4W (75%) compared to those treated with [[placebo]] (7%).<br />
<br />
For responders at Week 12 who were re-[[randomized]] to treatment withdrawal (i.e., [[placebo]]), the median time to relapse (sPGA ≥3) was 164 days in the integrated [[clinical trial|trials]]. Among these subjects, 66% regained a response of at least 0 or 1 on the sPGA within 12 weeks of restarting treatment with Ixekizumab 80 mg Q4W.<br />
|howSupplied=Ixekizumab injection is a sterile, [[preservative]] free, clear and colorless to slightly yellow solution available in a single-dose prefilled [[autoinjector]] or a single-dose prefilled [[syringe]] to deliver 80 mg ixekizumab.<br />
<br />
Ixekizumab is supplied as: <br />
|storage=Ixekizumab is sterile and preservative-free. Discard any unused portion.<br />
<br />
*Ixekizumab must be protected from light until use.<br />
*Store refrigerated at 2°C to 8°C (36°F to 46°F).<br />
*Do not freeze. Do not use Ixekizumab if it has been frozen.<br />
*Do not shake.<br />
*Discard the Ixekizumab single-dose [[autoinjector]] or [[syringe]] after use in a puncture-resistant container.<br />
*Not made with natural rubber latex.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233425
Ixekizumab
2016-05-30T10:18:56Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-[[interleukin 17|interleukin-17]] [[monoclonal antibody]]<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque]] [[psoriasis]] who are candidates for systemic therapy or [[phototherapy]]<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%)<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Moderate to severe [[plaque]] [[psoriasis]]=====<br />
======Dosage======<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
======Tuberculosis Assessment Prior to Initiation of Ixekizumab======<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
======Important Administration Instructions======<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
======Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]======<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions.<br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|useInPregnancyFDA=There are no available data on Ixekizumab use in pregnant women to inform any drug associated risks. Human [[IgG]] is known to cross the placental barrier; therefore, Ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.<br />
<br />
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.<br />
<br />
*Animal Data<br />
<br />
An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by [[subcutaneous injection]] during [[organogenesis]] to near [[parturition]] at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.<br />
<br />
In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly [[subcutaneous]] doses of ixekizumab up to 19 times the MRHD from the beginning of [[organogenesis]] to [[parturition]]. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or [[congenital defect]]. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.<br />
|useInNursing=There are no data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ixekizumab and any potential adverse effects on the breastfed infant from Ixekizumab or from the underlying maternal condition.<br />
|useInPed=The safety and effectiveness of Ixekizumab in pediatric patients (<18 years of age) have not been evaluated.<br />
|useInGeri=Of the 4204 [[psoriasis]] subjects exposed to Ixekizumab, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.<br />
|overdose=In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.<br />
|mechAction=Ixekizumab is a humanized IgG4 [[monoclonal antibody]] that selectively binds with the [[interleukin 17]]A (IL-17A) [[cytokine]] and inhibits its interaction with the [[interleukin 17|IL-17]] receptor. [[interleukin 17|IL-17A]] is a naturally occurring [[cytokine]] that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory [[cytokine]]s and [[chemokine]]s.<br />
|PD=No formal pharmacodynamic studies have been conducted with Ixekizumab.<br />
|PK=======Absorption======<br />
<br />
Following a single [[subcutaneous]] dose of 160 mg in subjects with [[psoriasis|plaque psoriasis]], ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.<br />
<br />
Steady-state concentrations were achieved by Week 8 following the 160 mg starting dose and 80 mg every 2 weeks dosing regimen; the mean ±SD steady-state trough concentration was 9.3 ±5.3 mcg/mL. Steady-state concentrations were achieved approximately 10 weeks after switching from the 80 mg every 2 weeks dosing regimen to the 80 mg every 4 weeks dosing regimen at Week 12. The mean ±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.<br />
<br />
In studies of subjects with plaque psoriasis, ixekizumab [[bioavailability]] ranged from 60% to 81% following [[subcutaneous]] injection. Administration of ixekizumab via injection in the thigh achieved a higher [[bioavailability]] relative to that achieved using other injection sites including the arm and abdomen.<br />
<br />
======Distribution======<br />
<br />
The mean (geometric CV%) [[volume of distribution]] at steady-state was 7.11 L (29%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
======Elimination======<br />
<br />
The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 [[monoclonal antibody]] ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous [[IgG]].<br />
<br />
The mean systemic clearance was 0.39 L/day (37%) and the mean (geometric CV%) [[half life]] was 13 days (40%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
*Weight<br />
<br />
Ixekizumab clearance and [[volume of distribution]] increase as body weight increases.<br />
<br />
*Dose Linearity<br />
Ixekizumab exhibited dose-proportional [[pharmacokinetics]] in subjects with [[psoriasis|plaque psoriasis]] over a dose range from 5 mg (not the recommended dose) to 160 mg following [[subcutaneous]] administration.<br />
|nonClinToxic=======[[Carcinogenesis]], [[Mutagenesis]], Impairment of Fertility======<br />
<br />
Animal studies have not been conducted to evaluate the [[carcinogenesis|carcinogenic]] or [[mutagenesis|mutagenic]] potential of Ixekizumab. Moreover published literature is mixed on potential effects on malignancy risk due to the inhibition of [[interleukin 17|IL-17A]] activity, the pharmacological action of Ixekizumab. Some published literature suggests that [[interleukin 17|IL-17A]] directly promotes cancer cell invasion, suggesting a potential beneficial effect by Ixekizumab, whereas other reports indicate [[interleukin 17|IL-17A]] promotes T-cell mediated tumor rejection, suggesting a potential adverse effect by Ixekizumab. However, neutralization of [[interleukin 17|IL-17A]] with Ixekizumab has not been studied in these models. Depletion of [[interleukin 17|IL-17A]] with a neutralizing [[antibody]] inhibited tumor development in mice, suggesting a potential beneficial effect by Ixekizumab. The relevance of experimental findings in mouse models for [[malignancy]] risk in humans is unknown.<br />
<br />
No effects on [[fertility]] parameters such as reproductive organs, [[menstrual cycle]] length, or [[sperm]] analysis were observed in sexually mature cynomolgus monkeys that were administered ixekizumab for 13 weeks at a [[subcutaneous]] dose of 50 mg/kg/week (19 times the MRHD on a mg/kg basis). The monkeys were not mated to evaluate [[fertility]].<br />
|clinicalStudies=Three multicenter, [[randomized]], [[double blind|double-blind]], [[placebo controlled|placebo-controlled]] [[clinical trial|trials]] (Trials 1, 2, and 3) enrolled a total of 3866 subjects 18 years of age and older with [[psoriasis|plaque psoriasis]] who had a minimum body surface area involvement of 10%, a static Physician Global Assessment (sPGA) score of ≥3 in the overall assessment ([[plaque]] thickness/[[induration]], [[erythema]], and scaling) of [[psoriasis]] on a severity scale of 0 to 5, a [[Psoriasis]] Area and Severity Index (PASI) score ≥12, and who were candidates for [[phototherapy]] or systemic therapy. <br />
<br />
In all three [[clinical trial|trials]], subjects were [[randomized]] to either [[placebo]] or Ixekizumab (80 mg every two weeks [Q2W]) for 12 weeks, following a 160 mg starting dose. In the two active comparator [[clinical trial|trials]] (Trials 2 and 3), subjects were also [[randomized]] to receive U.S. approved [[etanercept]] 50 mg twice weekly for 12 weeks. <br />
<br />
All three [[clinical trial|trials]] assessed the changes from baseline to Week 12 in the two co-primary endpoints: 1) PASI 75, the proportion of subjects who achieved at least a 75% reduction in the PASI composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of [[psoriasis|psoriatic]] changes ([[induration]], [[erythema]] and scaling) within the affected regions, and 2) sPGA of “0” (clear) or “1” (minimal), the proportion of subjects with an sPGA 0 or 1 and at least a 2-point improvement. <br />
<br />
Other evaluated outcomes included the proportion of subjects with an sPGA score of 0 (clear), a reduction of at least 90% in PASI (PASI 90), a reduction of 100% in PASI (PASI 100), and an improvement of itch severity as measured by a reduction of at least 4 points on an 11-point itch Numeric Rating Scale. <br />
<br />
Subjects in all treatment groups had a median baseline PASI score ranging from approximately 17 to 18. Baseline sPGA score was severe or very severe in 51% of subjects in Trial 1, 50% in Trial 2, and 48% in Trial 3. <br />
<br />
Of all subjects, 44% had received prior [[phototherapy]], 49% had received prior conventional systemic therapy, and 26% had received prior [[biologics|biologic therapy]] for the treatment of [[psoriasis]]. Of the subjects who had received prior [[biologics|biologic therapy]], 15% had received at least one [[TNF inhibitor|anti-TNF alpha agent]], and 9% had received an anti-IL 12/IL23. A total of 23% of study subjects had a history of [[psoriatic arthritis]]. <br />
<br />
======Clinical Response at Week 12======<br />
<br />
The results of Trials 1, 2, and 3 are presented in Table 2.<br />
<br />
Examination of age, gender, race, body weight, and previous treatment with a [[biologics|biologic]] did not identify differences in response to Ixekizumab among these subgroups at Week 12.<br />
<br />
Subjects treated with Ixekizumab 80 mg Q2W experienced improvement in [[itch]] severity when compared to placebo at Week 12.<br />
<br />
An integrated analysis of the U.S. sites in the two active comparator studies using U.S. approved [[etanercept]], Ixekizumab demonstrated superiority to U.S. approved [[etanercept]] (50 mg twice weekly) on sPGA and PASI scores during the 12 week treatment period. The respective response rates for Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]] 50 mg twice weekly were: sPGA of 0 or 1 (73% and 27%); PASI 75 (87% and 41%); sPGA of 0 (34% and 5%); PASI 90 (64% and 18%), and PASI 100 (34% and 4%).<br />
<br />
======Maintenance and Durability of Response======<br />
<br />
To evaluate the maintenance and durability of response, subjects originally [[randomized]] to Ixekizumab and who were responders at Week 12 (i.e., sPGA of 0 or 1) in Trial 1 and Trial 2 were re-randomized to an additional 48 weeks of either a maintenance dose of Ixekizumab 80 mg Q4W (every four weeks) or [[placebo]]. Non-responders (sPGA >1) at Week 12 and subjects who relapsed (sPGA ≥3) during the maintenance period were placed on Ixekizumab 80 mg Q4W.<br />
<br />
For responders at Week 12, the percentage of subjects who maintained this response (sPGA 0 or 1) at Week 60 (48 weeks following re-[[randomization]]) in the integrated [[clinical trial|trials]] (Trial 1 and Trial 2) was higher for subjects treated with Ixekizumab 80 mg Q4W (75%) compared to those treated with [[placebo]] (7%).<br />
<br />
For responders at Week 12 who were re-[[randomized]] to treatment withdrawal (i.e., [[placebo]]), the median time to relapse (sPGA ≥3) was 164 days in the integrated [[clinical trial|trials]]. Among these subjects, 66% regained a response of at least 0 or 1 on the sPGA within 12 weeks of restarting treatment with Ixekizumab 80 mg Q4W.<br />
|storage=Ixekizumab is sterile and preservative-free. Discard any unused portion.<br />
<br />
*Ixekizumab must be protected from light until use.<br />
*Store refrigerated at 2°C to 8°C (36°F to 46°F).<br />
*Do not freeze. Do not use Ixekizumab if it has been frozen.<br />
*Do not shake.<br />
*Discard the Ixekizumab single-dose [[autoinjector]] or [[syringe]] after use in a puncture-resistant container.<br />
*Not made with natural rubber latex.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233424
Ixekizumab
2016-05-30T09:32:50Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-[[interleukin 17|interleukin-17]] [[monoclonal antibody]]<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque]] [[psoriasis]] who are candidates for systemic therapy or [[phototherapy]]<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%)<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Moderate to severe [[plaque]] [[psoriasis]]=====<br />
======Dosage======<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
======Tuberculosis Assessment Prior to Initiation of Ixekizumab======<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
======Important Administration Instructions======<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
======Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]======<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions.<br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|useInPregnancyFDA=There are no available data on Ixekizumab use in pregnant women to inform any drug associated risks. Human [[IgG]] is known to cross the placental barrier; therefore, Ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.<br />
<br />
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.<br />
<br />
*Animal Data<br />
<br />
An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by [[subcutaneous injection]] during [[organogenesis]] to near [[parturition]] at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.<br />
<br />
In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly [[subcutaneous]] doses of ixekizumab up to 19 times the MRHD from the beginning of [[organogenesis]] to [[parturition]]. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or [[congenital defect]]. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.<br />
|useInNursing=There are no data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ixekizumab and any potential adverse effects on the breastfed infant from Ixekizumab or from the underlying maternal condition.<br />
|useInPed=The safety and effectiveness of Ixekizumab in pediatric patients (<18 years of age) have not been evaluated.<br />
|useInGeri=Of the 4204 [[psoriasis]] subjects exposed to Ixekizumab, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.<br />
|overdose=In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.<br />
|mechAction=Ixekizumab is a humanized IgG4 [[monoclonal antibody]] that selectively binds with the [[interleukin 17]]A (IL-17A) [[cytokine]] and inhibits its interaction with the [[interleukin 17|IL-17]] receptor. [[interleukin 17|IL-17A]] is a naturally occurring [[cytokine]] that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory [[cytokine]]s and [[chemokine]]s.<br />
|PD=No formal pharmacodynamic studies have been conducted with Ixekizumab.<br />
|PK=======Absorption======<br />
<br />
Following a single [[subcutaneous]] dose of 160 mg in subjects with [[psoriasis|plaque psoriasis]], ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.<br />
<br />
Steady-state concentrations were achieved by Week 8 following the 160 mg starting dose and 80 mg every 2 weeks dosing regimen; the mean ±SD steady-state trough concentration was 9.3 ±5.3 mcg/mL. Steady-state concentrations were achieved approximately 10 weeks after switching from the 80 mg every 2 weeks dosing regimen to the 80 mg every 4 weeks dosing regimen at Week 12. The mean ±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.<br />
<br />
In studies of subjects with plaque psoriasis, ixekizumab [[bioavailability]] ranged from 60% to 81% following [[subcutaneous]] injection. Administration of ixekizumab via injection in the thigh achieved a higher [[bioavailability]] relative to that achieved using other injection sites including the arm and abdomen.<br />
<br />
======Distribution======<br />
<br />
The mean (geometric CV%) [[volume of distribution]] at steady-state was 7.11 L (29%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
======Elimination======<br />
<br />
The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 [[monoclonal antibody]] ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous [[IgG]].<br />
<br />
The mean systemic clearance was 0.39 L/day (37%) and the mean (geometric CV%) [[half life]] was 13 days (40%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
*Weight<br />
<br />
Ixekizumab clearance and [[volume of distribution]] increase as body weight increases.<br />
<br />
*Dose Linearity<br />
Ixekizumab exhibited dose-proportional [[pharmacokinetics]] in subjects with [[psoriasis|plaque psoriasis]] over a dose range from 5 mg (not the recommended dose) to 160 mg following [[subcutaneous]] administration.<br />
|nonClinToxic=======[[Carcinogenesis]], [[Mutagenesis]], Impairment of Fertility======<br />
<br />
Animal studies have not been conducted to evaluate the [[carcinogenesis|carcinogenic]] or [[mutagenesis|mutagenic]] potential of Ixekizumab. Moreover published literature is mixed on potential effects on malignancy risk due to the inhibition of [[interleukin 17|IL-17A]] activity, the pharmacological action of Ixekizumab. Some published literature suggests that [[interleukin 17|IL-17A]] directly promotes cancer cell invasion, suggesting a potential beneficial effect by Ixekizumab, whereas other reports indicate [[interleukin 17|IL-17A]] promotes T-cell mediated tumor rejection, suggesting a potential adverse effect by Ixekizumab. However, neutralization of [[interleukin 17|IL-17A]] with Ixekizumab has not been studied in these models. Depletion of [[interleukin 17|IL-17A]] with a neutralizing [[antibody]] inhibited tumor development in mice, suggesting a potential beneficial effect by Ixekizumab. The relevance of experimental findings in mouse models for [[malignancy]] risk in humans is unknown.<br />
<br />
No effects on [[fertility]] parameters such as reproductive organs, [[menstrual cycle]] length, or [[sperm]] analysis were observed in sexually mature cynomolgus monkeys that were administered ixekizumab for 13 weeks at a [[subcutaneous]] dose of 50 mg/kg/week (19 times the MRHD on a mg/kg basis). The monkeys were not mated to evaluate [[fertility]].<br />
|clinicalStudies=Three multicenter, [[randomized]], [[double blind|double-blind]], [[placebo controlled|placebo-controlled]] [[clinical trial|trials]] (Trials 1, 2, and 3) enrolled a total of 3866 subjects 18 years of age and older with [[psoriasis|plaque psoriasis]] who had a minimum body surface area involvement of 10%, a static Physician Global Assessment (sPGA) score of ≥3 in the overall assessment ([[plaque]] thickness/[[induration]], [[erythema]], and scaling) of [[psoriasis]] on a severity scale of 0 to 5, a [[Psoriasis]] Area and Severity Index (PASI) score ≥12, and who were candidates for [[phototherapy]] or systemic therapy. <br />
<br />
In all three [[clinical trial|trials]], subjects were [[randomized]] to either [[placebo]] or Ixekizumab (80 mg every two weeks [Q2W]) for 12 weeks, following a 160 mg starting dose. In the two active comparator [[clinical trial|trials]] (Trials 2 and 3), subjects were also [[randomized]] to receive U.S. approved [[etanercept]] 50 mg twice weekly for 12 weeks. <br />
<br />
All three [[clinical trial|trials]] assessed the changes from baseline to Week 12 in the two co-primary endpoints: 1) PASI 75, the proportion of subjects who achieved at least a 75% reduction in the PASI composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of [[psoriasis|psoriatic]] changes ([[induration]], [[erythema]] and scaling) within the affected regions, and 2) sPGA of “0” (clear) or “1” (minimal), the proportion of subjects with an sPGA 0 or 1 and at least a 2-point improvement. <br />
<br />
Other evaluated outcomes included the proportion of subjects with an sPGA score of 0 (clear), a reduction of at least 90% in PASI (PASI 90), a reduction of 100% in PASI (PASI 100), and an improvement of itch severity as measured by a reduction of at least 4 points on an 11-point itch Numeric Rating Scale. <br />
<br />
Subjects in all treatment groups had a median baseline PASI score ranging from approximately 17 to 18. Baseline sPGA score was severe or very severe in 51% of subjects in Trial 1, 50% in Trial 2, and 48% in Trial 3. <br />
<br />
Of all subjects, 44% had received prior [[phototherapy]], 49% had received prior conventional systemic therapy, and 26% had received prior [[biologics|biologic therapy]] for the treatment of [[psoriasis]]. Of the subjects who had received prior [[biologics|biologic therapy]], 15% had received at least one [[TNF inhibitor|anti-TNF alpha agent]], and 9% had received an anti-IL 12/IL23. A total of 23% of study subjects had a history of [[psoriatic arthritis]]. <br />
<br />
======Clinical Response at Week 12======<br />
<br />
The results of Trials 1, 2, and 3 are presented in Table 2.<br />
<br />
Examination of age, gender, race, body weight, and previous treatment with a [[biologics|biologic]] did not identify differences in response to Ixekizumab among these subgroups at Week 12.<br />
<br />
Subjects treated with Ixekizumab 80 mg Q2W experienced improvement in [[itch]] severity when compared to placebo at Week 12.<br />
<br />
An integrated analysis of the U.S. sites in the two active comparator studies using U.S. approved [[etanercept]], Ixekizumab demonstrated superiority to U.S. approved [[etanercept]] (50 mg twice weekly) on sPGA and PASI scores during the 12 week treatment period. The respective response rates for Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]] 50 mg twice weekly were: sPGA of 0 or 1 (73% and 27%); PASI 75 (87% and 41%); sPGA of 0 (34% and 5%); PASI 90 (64% and 18%), and PASI 100 (34% and 4%).<br />
<br />
======Maintenance and Durability of Response======<br />
<br />
To evaluate the maintenance and durability of response, subjects originally [[randomized]] to Ixekizumab and who were responders at Week 12 (i.e., sPGA of 0 or 1) in Trial 1 and Trial 2 were re-randomized to an additional 48 weeks of either a maintenance dose of Ixekizumab 80 mg Q4W (every four weeks) or [[placebo]]. Non-responders (sPGA >1) at Week 12 and subjects who relapsed (sPGA ≥3) during the maintenance period were placed on Ixekizumab 80 mg Q4W.<br />
<br />
For responders at Week 12, the percentage of subjects who maintained this response (sPGA 0 or 1) at Week 60 (48 weeks following re-[[randomization]]) in the integrated [[clinical trial|trials]] (Trial 1 and Trial 2) was higher for subjects treated with Ixekizumab 80 mg Q4W (75%) compared to those treated with [[placebo]] (7%).<br />
<br />
For responders at Week 12 who were re-[[randomized]] to treatment withdrawal (i.e., [[placebo]]), the median time to relapse (sPGA ≥3) was 164 days in the integrated [[clinical trial|trials]]. Among these subjects, 66% regained a response of at least 0 or 1 on the sPGA within 12 weeks of restarting treatment with Ixekizumab 80 mg Q4W.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233423
Ixekizumab
2016-05-30T09:25:46Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-[[interleukin 17|interleukin-17]] [[monoclonal antibody]]<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque]] [[psoriasis]] who are candidates for systemic therapy or [[phototherapy]]<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%)<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Moderate to severe [[plaque]] [[psoriasis]]=====<br />
======Dosage======<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
======Tuberculosis Assessment Prior to Initiation of Ixekizumab======<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
======Important Administration Instructions======<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
======Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]======<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions.<br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|useInPregnancyFDA=There are no available data on Ixekizumab use in pregnant women to inform any drug associated risks. Human [[IgG]] is known to cross the placental barrier; therefore, Ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.<br />
<br />
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.<br />
<br />
*Animal Data<br />
<br />
An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by [[subcutaneous injection]] during [[organogenesis]] to near [[parturition]] at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.<br />
<br />
In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly [[subcutaneous]] doses of ixekizumab up to 19 times the MRHD from the beginning of [[organogenesis]] to [[parturition]]. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or [[congenital defect]]. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.<br />
|useInNursing=There are no data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ixekizumab and any potential adverse effects on the breastfed infant from Ixekizumab or from the underlying maternal condition.<br />
|useInPed=The safety and effectiveness of Ixekizumab in pediatric patients (<18 years of age) have not been evaluated.<br />
|useInGeri=Of the 4204 [[psoriasis]] subjects exposed to Ixekizumab, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.<br />
|overdose=In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.<br />
|mechAction=Ixekizumab is a humanized IgG4 [[monoclonal antibody]] that selectively binds with the [[interleukin 17]]A (IL-17A) [[cytokine]] and inhibits its interaction with the [[interleukin 17|IL-17]] receptor. [[interleukin 17|IL-17A]] is a naturally occurring [[cytokine]] that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory [[cytokine]]s and [[chemokine]]s.<br />
|PD=No formal pharmacodynamic studies have been conducted with Ixekizumab.<br />
|PK=======Absorption======<br />
<br />
Following a single [[subcutaneous]] dose of 160 mg in subjects with [[psoriasis|plaque psoriasis]], ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.<br />
<br />
Steady-state concentrations were achieved by Week 8 following the 160 mg starting dose and 80 mg every 2 weeks dosing regimen; the mean ±SD steady-state trough concentration was 9.3 ±5.3 mcg/mL. Steady-state concentrations were achieved approximately 10 weeks after switching from the 80 mg every 2 weeks dosing regimen to the 80 mg every 4 weeks dosing regimen at Week 12. The mean ±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.<br />
<br />
In studies of subjects with plaque psoriasis, ixekizumab [[bioavailability]] ranged from 60% to 81% following [[subcutaneous]] injection. Administration of ixekizumab via injection in the thigh achieved a higher [[bioavailability]] relative to that achieved using other injection sites including the arm and abdomen.<br />
<br />
======Distribution======<br />
<br />
The mean (geometric CV%) [[volume of distribution]] at steady-state was 7.11 L (29%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
======Elimination======<br />
<br />
The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 [[monoclonal antibody]] ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous [[IgG]].<br />
<br />
The mean systemic clearance was 0.39 L/day (37%) and the mean (geometric CV%) [[half life]] was 13 days (40%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
*Weight<br />
<br />
Ixekizumab clearance and [[volume of distribution]] increase as body weight increases.<br />
<br />
*Dose Linearity<br />
Ixekizumab exhibited dose-proportional [[pharmacokinetics]] in subjects with [[psoriasis|plaque psoriasis]] over a dose range from 5 mg (not the recommended dose) to 160 mg following [[subcutaneous]] administration.<br />
|clinicalStudies=Three multicenter, [[randomized]], [[double blind|double-blind]], [[placebo controlled|placebo-controlled]] [[clinical trial|trials]] (Trials 1, 2, and 3) enrolled a total of 3866 subjects 18 years of age and older with [[psoriasis|plaque psoriasis]] who had a minimum body surface area involvement of 10%, a static Physician Global Assessment (sPGA) score of ≥3 in the overall assessment ([[plaque]] thickness/[[induration]], [[erythema]], and scaling) of [[psoriasis]] on a severity scale of 0 to 5, a [[Psoriasis]] Area and Severity Index (PASI) score ≥12, and who were candidates for [[phototherapy]] or systemic therapy. <br />
<br />
In all three [[clinical trial|trials]], subjects were [[randomized]] to either [[placebo]] or Ixekizumab (80 mg every two weeks [Q2W]) for 12 weeks, following a 160 mg starting dose. In the two active comparator [[clinical trial|trials]] (Trials 2 and 3), subjects were also [[randomized]] to receive U.S. approved [[etanercept]] 50 mg twice weekly for 12 weeks. <br />
<br />
All three [[clinical trial|trials]] assessed the changes from baseline to Week 12 in the two co-primary endpoints: 1) PASI 75, the proportion of subjects who achieved at least a 75% reduction in the PASI composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of [[psoriasis|psoriatic]] changes ([[induration]], [[erythema]] and scaling) within the affected regions, and 2) sPGA of “0” (clear) or “1” (minimal), the proportion of subjects with an sPGA 0 or 1 and at least a 2-point improvement. <br />
<br />
Other evaluated outcomes included the proportion of subjects with an sPGA score of 0 (clear), a reduction of at least 90% in PASI (PASI 90), a reduction of 100% in PASI (PASI 100), and an improvement of itch severity as measured by a reduction of at least 4 points on an 11-point itch Numeric Rating Scale. <br />
<br />
Subjects in all treatment groups had a median baseline PASI score ranging from approximately 17 to 18. Baseline sPGA score was severe or very severe in 51% of subjects in Trial 1, 50% in Trial 2, and 48% in Trial 3. <br />
<br />
Of all subjects, 44% had received prior [[phototherapy]], 49% had received prior conventional systemic therapy, and 26% had received prior [[biologics|biologic therapy]] for the treatment of [[psoriasis]]. Of the subjects who had received prior [[biologics|biologic therapy]], 15% had received at least one [[TNF inhibitor|anti-TNF alpha agent]], and 9% had received an anti-IL 12/IL23. A total of 23% of study subjects had a history of [[psoriatic arthritis]]. <br />
<br />
======Clinical Response at Week 12======<br />
<br />
The results of Trials 1, 2, and 3 are presented in Table 2.<br />
<br />
Examination of age, gender, race, body weight, and previous treatment with a [[biologics|biologic]] did not identify differences in response to Ixekizumab among these subgroups at Week 12.<br />
<br />
Subjects treated with Ixekizumab 80 mg Q2W experienced improvement in [[itch]] severity when compared to placebo at Week 12.<br />
<br />
An integrated analysis of the U.S. sites in the two active comparator studies using U.S. approved [[etanercept]], Ixekizumab demonstrated superiority to U.S. approved [[etanercept]] (50 mg twice weekly) on sPGA and PASI scores during the 12 week treatment period. The respective response rates for Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]] 50 mg twice weekly were: sPGA of 0 or 1 (73% and 27%); PASI 75 (87% and 41%); sPGA of 0 (34% and 5%); PASI 90 (64% and 18%), and PASI 100 (34% and 4%).<br />
<br />
======Maintenance and Durability of Response======<br />
<br />
To evaluate the maintenance and durability of response, subjects originally [[randomized]] to Ixekizumab and who were responders at Week 12 (i.e., sPGA of 0 or 1) in Trial 1 and Trial 2 were re-randomized to an additional 48 weeks of either a maintenance dose of Ixekizumab 80 mg Q4W (every four weeks) or [[placebo]]. Non-responders (sPGA >1) at Week 12 and subjects who relapsed (sPGA ≥3) during the maintenance period were placed on Ixekizumab 80 mg Q4W.<br />
<br />
For responders at Week 12, the percentage of subjects who maintained this response (sPGA 0 or 1) at Week 60 (48 weeks following re-[[randomization]]) in the integrated [[clinical trial|trials]] (Trial 1 and Trial 2) was higher for subjects treated with Ixekizumab 80 mg Q4W (75%) compared to those treated with [[placebo]] (7%).<br />
<br />
For responders at Week 12 who were re-[[randomized]] to treatment withdrawal (i.e., [[placebo]]), the median time to relapse (sPGA ≥3) was 164 days in the integrated [[clinical trial|trials]]. Among these subjects, 66% regained a response of at least 0 or 1 on the sPGA within 12 weeks of restarting treatment with Ixekizumab 80 mg Q4W.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233422
Ixekizumab
2016-05-30T09:14:17Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-[[interleukin 17|interleukin-17]] [[monoclonal antibody]]<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque]] [[psoriasis]] who are candidates for systemic therapy or [[phototherapy]]<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%)<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Moderate to severe [[plaque]] [[psoriasis]]=====<br />
======Dosage======<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
======Tuberculosis Assessment Prior to Initiation of Ixekizumab======<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
======Important Administration Instructions======<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
======Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]======<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions.<br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|useInPregnancyFDA=There are no available data on Ixekizumab use in pregnant women to inform any drug associated risks. Human [[IgG]] is known to cross the placental barrier; therefore, Ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.<br />
<br />
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.<br />
<br />
*Animal Data<br />
<br />
An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by [[subcutaneous injection]] during [[organogenesis]] to near [[parturition]] at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.<br />
<br />
In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly [[subcutaneous]] doses of ixekizumab up to 19 times the MRHD from the beginning of [[organogenesis]] to [[parturition]]. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or [[congenital defect]]. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.<br />
|useInNursing=There are no data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ixekizumab and any potential adverse effects on the breastfed infant from Ixekizumab or from the underlying maternal condition.<br />
|useInPed=The safety and effectiveness of Ixekizumab in pediatric patients (<18 years of age) have not been evaluated.<br />
|useInGeri=Of the 4204 [[psoriasis]] subjects exposed to Ixekizumab, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.<br />
|overdose=In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.<br />
|mechAction=Ixekizumab is a humanized IgG4 [[monoclonal antibody]] that selectively binds with the [[interleukin 17]]A (IL-17A) [[cytokine]] and inhibits its interaction with the [[interleukin 17|IL-17]] receptor. [[interleukin 17|IL-17A]] is a naturally occurring [[cytokine]] that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory [[cytokine]]s and [[chemokine]]s.<br />
|PD=No formal pharmacodynamic studies have been conducted with Ixekizumab.<br />
|PK=======Absorption======<br />
<br />
Following a single [[subcutaneous]] dose of 160 mg in subjects with [[psoriasis|plaque psoriasis]], ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.<br />
<br />
Steady-state concentrations were achieved by Week 8 following the 160 mg starting dose and 80 mg every 2 weeks dosing regimen; the mean ±SD steady-state trough concentration was 9.3 ±5.3 mcg/mL. Steady-state concentrations were achieved approximately 10 weeks after switching from the 80 mg every 2 weeks dosing regimen to the 80 mg every 4 weeks dosing regimen at Week 12. The mean ±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.<br />
<br />
In studies of subjects with plaque psoriasis, ixekizumab [[bioavailability]] ranged from 60% to 81% following [[subcutaneous]] injection. Administration of ixekizumab via injection in the thigh achieved a higher [[bioavailability]] relative to that achieved using other injection sites including the arm and abdomen.<br />
<br />
======Distribution======<br />
<br />
The mean (geometric CV%) [[volume of distribution]] at steady-state was 7.11 L (29%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
======Elimination======<br />
<br />
The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 [[monoclonal antibody]] ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous [[IgG]].<br />
<br />
The mean systemic clearance was 0.39 L/day (37%) and the mean (geometric CV%) [[half life]] was 13 days (40%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
*Weight<br />
<br />
Ixekizumab clearance and [[volume of distribution]] increase as body weight increases.<br />
<br />
*Dose Linearity<br />
Ixekizumab exhibited dose-proportional [[pharmacokinetics]] in subjects with [[psoriasis|plaque psoriasis]] over a dose range from 5 mg (not the recommended dose) to 160 mg following [[subcutaneous]] administration.<br />
|clinicalStudies=Three multicenter, [[randomized]], [[double blind|double-blind]], [[placebo controlled|placebo-controlled]] [[clinical trial|trials]] (Trials 1, 2, and 3) enrolled a total of 3866 subjects 18 years of age and older with [[psoriasis|plaque psoriasis]] who had a minimum body surface area involvement of 10%, a static Physician Global Assessment (sPGA) score of ≥3 in the overall assessment ([[plaque]] thickness/[[induration]], [[erythema]], and scaling) of [[psoriasis]] on a severity scale of 0 to 5, a [[Psoriasis]] Area and Severity Index (PASI) score ≥12, and who were candidates for [[phototherapy]] or systemic therapy. <br />
<br />
In all three [[clinical trial|trials]], subjects were [[randomized]] to either [[placebo]] or Ixekizumab (80 mg every two weeks [Q2W]) for 12 weeks, following a 160 mg starting dose. In the two active comparator [[clinical trial|trials]] (Trials 2 and 3), subjects were also [[randomized]] to receive U.S. approved [[etanercept]] 50 mg twice weekly for 12 weeks. <br />
<br />
All three [[clinical trial|trials]] assessed the changes from baseline to Week 12 in the two co-primary endpoints: 1) PASI 75, the proportion of subjects who achieved at least a 75% reduction in the PASI composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of [[psoriasis|psoriatic]] changes ([[induration]], [[erythema]] and scaling) within the affected regions, and 2) sPGA of “0” (clear) or “1” (minimal), the proportion of subjects with an sPGA 0 or 1 and at least a 2-point improvement. <br />
<br />
Other evaluated outcomes included the proportion of subjects with an sPGA score of 0 (clear), a reduction of at least 90% in PASI (PASI 90), a reduction of 100% in PASI (PASI 100), and an improvement of itch severity as measured by a reduction of at least 4 points on an 11-point itch Numeric Rating Scale. <br />
<br />
Subjects in all treatment groups had a median baseline PASI score ranging from approximately 17 to 18. Baseline sPGA score was severe or very severe in 51% of subjects in Trial 1, 50% in Trial 2, and 48% in Trial 3. <br />
<br />
Of all subjects, 44% had received prior [[phototherapy]], 49% had received prior conventional systemic therapy, and 26% had received prior [[biologics|biologic therapy]] for the treatment of [[psoriasis]]. Of the subjects who had received prior [[biologics|biologic therapy]], 15% had received at least one [[TNF inhibitor|anti-TNF alpha agent]], and 9% had received an anti-IL 12/IL23. A total of 23% of study subjects had a history of [[psoriatic arthritis]]. <br />
<br />
======Clinical Response at Week 12====== <br />
<br />
The results of Trials 1, 2, and 3 are presented in Table 2.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233421
Ixekizumab
2016-05-30T06:51:23Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-[[interleukin 17|interleukin-17]] [[monoclonal antibody]]<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque]] [[psoriasis]] who are candidates for systemic therapy or [[phototherapy]]<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%)<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Moderate to severe [[plaque]] [[psoriasis]]=====<br />
======Dosage======<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
======Tuberculosis Assessment Prior to Initiation of Ixekizumab======<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
======Important Administration Instructions======<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
======Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]======<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions.<br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|useInPregnancyFDA=There are no available data on Ixekizumab use in pregnant women to inform any drug associated risks. Human [[IgG]] is known to cross the placental barrier; therefore, Ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.<br />
<br />
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.<br />
<br />
*Animal Data<br />
<br />
An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by [[subcutaneous injection]] during [[organogenesis]] to near [[parturition]] at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.<br />
<br />
In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly [[subcutaneous]] doses of ixekizumab up to 19 times the MRHD from the beginning of [[organogenesis]] to [[parturition]]. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or [[congenital defect]]. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.<br />
|useInNursing=There are no data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ixekizumab and any potential adverse effects on the breastfed infant from Ixekizumab or from the underlying maternal condition.<br />
|useInPed=The safety and effectiveness of Ixekizumab in pediatric patients (<18 years of age) have not been evaluated.<br />
|useInGeri=Of the 4204 [[psoriasis]] subjects exposed to Ixekizumab, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.<br />
|overdose=In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.<br />
|mechAction=Ixekizumab is a humanized IgG4 [[monoclonal antibody]] that selectively binds with the [[interleukin 17]]A (IL-17A) [[cytokine]] and inhibits its interaction with the [[interleukin 17|IL-17]] receptor. [[interleukin 17|IL-17A]] is a naturally occurring [[cytokine]] that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory [[cytokine]]s and [[chemokine]]s.<br />
|PD=No formal pharmacodynamic studies have been conducted with Ixekizumab.<br />
|PK=======Absorption======<br />
<br />
Following a single [[subcutaneous]] dose of 160 mg in subjects with [[psoriasis|plaque psoriasis]], ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.<br />
<br />
Steady-state concentrations were achieved by Week 8 following the 160 mg starting dose and 80 mg every 2 weeks dosing regimen; the mean ±SD steady-state trough concentration was 9.3 ±5.3 mcg/mL. Steady-state concentrations were achieved approximately 10 weeks after switching from the 80 mg every 2 weeks dosing regimen to the 80 mg every 4 weeks dosing regimen at Week 12. The mean ±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.<br />
<br />
In studies of subjects with plaque psoriasis, ixekizumab [[bioavailability]] ranged from 60% to 81% following [[subcutaneous]] injection. Administration of ixekizumab via injection in the thigh achieved a higher [[bioavailability]] relative to that achieved using other injection sites including the arm and abdomen.<br />
<br />
======Distribution======<br />
<br />
The mean (geometric CV%) [[volume of distribution]] at steady-state was 7.11 L (29%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
======Elimination======<br />
<br />
The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 [[monoclonal antibody]] ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous [[IgG]].<br />
<br />
The mean systemic clearance was 0.39 L/day (37%) and the mean (geometric CV%) [[half life]] was 13 days (40%) in subjects with [[psoriasis|plaque psoriasis]].<br />
<br />
*Weight<br />
<br />
Ixekizumab clearance and [[volume of distribution]] increase as body weight increases.<br />
<br />
*Dose Linearity<br />
Ixekizumab exhibited dose-proportional [[pharmacokinetics]] in subjects with [[psoriasis|plaque psoriasis]] over a dose range from 5 mg (not the recommended dose) to 160 mg following [[subcutaneous]] administration.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233420
Ixekizumab
2016-05-30T06:38:21Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-[[interleukin 17|interleukin-17]] [[monoclonal antibody]]<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque]] [[psoriasis]] who are candidates for systemic therapy or [[phototherapy]]<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%)<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Moderate to severe [[plaque]] [[psoriasis]]=====<br />
======Dosage======<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
======Tuberculosis Assessment Prior to Initiation of Ixekizumab======<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
======Important Administration Instructions======<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
======Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]======<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions.<br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|useInPregnancyFDA=There are no available data on Ixekizumab use in pregnant women to inform any drug associated risks. Human [[IgG]] is known to cross the placental barrier; therefore, Ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.<br />
<br />
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.<br />
<br />
*Animal Data<br />
<br />
An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by [[subcutaneous injection]] during [[organogenesis]] to near [[parturition]] at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.<br />
<br />
In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly [[subcutaneous]] doses of ixekizumab up to 19 times the MRHD from the beginning of [[organogenesis]] to [[parturition]]. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or [[congenital defect]]. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.<br />
|useInNursing=There are no data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ixekizumab and any potential adverse effects on the breastfed infant from Ixekizumab or from the underlying maternal condition.<br />
|useInPed=The safety and effectiveness of Ixekizumab in pediatric patients (<18 years of age) have not been evaluated.<br />
|useInGeri=Of the 4204 [[psoriasis]] subjects exposed to Ixekizumab, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.<br />
|overdose=In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.<br />
|mechAction=Ixekizumab is a humanized IgG4 [[monoclonal antibody]] that selectively binds with the [[interleukin 17]]A (IL-17A) [[cytokine]] and inhibits its interaction with the [[interleukin 17|IL-17]] receptor. [[interleukin 17|IL-17A]] is a naturally occurring [[cytokine]] that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory [[cytokine]]s and [[chemokine]]s.<br />
|PD=No formal pharmacodynamic studies have been conducted with Ixekizumab.<br />
|PK=====Absorption====<br />
<br />
Following a single [[subcutaneous]] dose of 160 mg in subjects with [[psoriasis|plaque psoriasis]], ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.<br />
<br />
Steady-state concentrations were achieved by Week 8 following the 160 mg starting dose and 80 mg every 2 weeks dosing regimen; the mean ±SD steady-state trough concentration was 9.3 ±5.3 mcg/mL. Steady-state concentrations were achieved approximately 10 weeks after switching from the 80 mg every 2 weeks dosing regimen to the 80 mg every 4 weeks dosing regimen at Week 12. The mean ±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.<br />
<br />
In studies of subjects with plaque psoriasis, ixekizumab bioavailability ranged from 60% to 81% following subcutaneous injection. Administration of ixekizumab via injection in the thigh achieved a higher bioavailability relative to that achieved using other injection sites including the arm and abdomen.<br />
<br />
Distribution<br />
<br />
The mean (geometric CV%) volume of distribution at steady-state was 7.11 L (29%) in subjects with plaque psoriasis.<br />
<br />
Elimination<br />
<br />
The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 monoclonal antibody ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.<br />
<br />
The mean systemic clearance was 0.39 L/day (37%) and the mean (geometric CV%) half-life was 13 days (40%) in subjects with plaque psoriasis.<br />
<br />
Weight<br />
<br />
Ixekizumab clearance and volume of distribution increase as body weight increases.<br />
<br />
Dose Linearity<br />
<br />
Ixekizumab exhibited dose-proportional pharmacokinetics in subjects with plaque psoriasis over a dose range from 5 mg (not the recommended dose) to 160 mg following subcutaneous administration.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233419
Ixekizumab
2016-05-30T06:04:01Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-[[interleukin 17|interleukin-17]] [[monoclonal antibody]]<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque]] [[psoriasis]] who are candidates for systemic therapy or [[phototherapy]]<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%)<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Moderate to severe [[plaque]] [[psoriasis]]=====<br />
======Dosage======<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
======Tuberculosis Assessment Prior to Initiation of Ixekizumab======<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
======Important Administration Instructions======<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
======Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]======<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions.<br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|useInPregnancyFDA=There are no available data on Ixekizumab use in pregnant women to inform any drug associated risks. Human [[IgG]] is known to cross the placental barrier; therefore, Ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.<br />
<br />
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.<br />
<br />
*Animal Data<br />
<br />
An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by [[subcutaneous injection]] during [[organogenesis]] to near [[parturition]] at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.<br />
<br />
In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly [[subcutaneous]] doses of ixekizumab up to 19 times the MRHD from the beginning of [[organogenesis]] to [[parturition]]. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or [[congenital defect]]. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.<br />
|useInNursing=There are no data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ixekizumab and any potential adverse effects on the breastfed infant from Ixekizumab or from the underlying maternal condition.<br />
|useInPed=The safety and effectiveness of Ixekizumab in pediatric patients (<18 years of age) have not been evaluated.<br />
|useInGeri=Of the 4204 [[psoriasis]] subjects exposed to Ixekizumab, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.<br />
|overdose=In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.<br />
|mechAction=Ixekizumab is a humanized IgG4 [[monoclonal antibody]] that selectively binds with the interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory cytokines and chemokines.<br />
|PD=No formal pharmacodynamic studies have been conducted with TALTZ.<br />
|PK=bsorption<br />
<br />
Following a single subcutaneous dose of 160 mg in subjects with plaque psoriasis, ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.<br />
<br />
Steady-state concentrations were achieved by Week 8 following the 160 mg starting dose and 80 mg every 2 weeks dosing regimen; the mean ±SD steady-state trough concentration was 9.3 ±5.3 mcg/mL. Steady-state concentrations were achieved approximately 10 weeks after switching from the 80 mg every 2 weeks dosing regimen to the 80 mg every 4 weeks dosing regimen at Week 12. The mean ±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.<br />
<br />
In studies of subjects with plaque psoriasis, ixekizumab bioavailability ranged from 60% to 81% following subcutaneous injection. Administration of ixekizumab via injection in the thigh achieved a higher bioavailability relative to that achieved using other injection sites including the arm and abdomen.<br />
<br />
Distribution<br />
<br />
The mean (geometric CV%) volume of distribution at steady-state was 7.11 L (29%) in subjects with plaque psoriasis.<br />
<br />
Elimination<br />
<br />
The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 monoclonal antibody ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.<br />
<br />
The mean systemic clearance was 0.39 L/day (37%) and the mean (geometric CV%) half-life was 13 days (40%) in subjects with plaque psoriasis.<br />
<br />
Weight<br />
<br />
Ixekizumab clearance and volume of distribution increase as body weight increases.<br />
<br />
Dose Linearity<br />
<br />
Ixekizumab exhibited dose-proportional pharmacokinetics in subjects with plaque psoriasis over a dose range from 5 mg (not the recommended dose) to 160 mg following subcutaneous administration.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233418
Ixekizumab
2016-05-30T05:02:16Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-[[interleukin 17|interleukin-17]] [[monoclonal antibody]]<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque]] [[psoriasis]] who are candidates for systemic therapy or [[phototherapy]]<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%)<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Dosage=====<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
=====Tuberculosis Assessment Prior to Initiation of Ixekizumab=====<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
=====Important Administration Instructions=====<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
=====Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]=====<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions.<br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|useInPregnancyFDA=There are no available data on Ixekizumab use in pregnant women to inform any drug associated risks. Human [[IgG]] is known to cross the placental barrier; therefore, Ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.<br />
<br />
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.<br />
<br />
*Animal Data<br />
<br />
An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by [[subcutaneous injection]] during [[organogenesis]] to near [[parturition]] at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.<br />
<br />
In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly [[subcutaneous]] doses of ixekizumab up to 19 times the MRHD from the beginning of [[organogenesis]] to [[parturition]]. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or [[congenital defect]]. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.<br />
|useInNursing=There are no data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ixekizumab and any potential adverse effects on the breastfed infant from Ixekizumab or from the underlying maternal condition.<br />
|useInPed=The safety and effectiveness of Ixekizumab in pediatric patients (<18 years of age) have not been evaluated.<br />
|useInGeri=Of the 4204 [[psoriasis]] subjects exposed to Ixekizumab, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.<br />
|overdose=In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.<br />
|mechAction=Ixekizumab is a humanized IgG4 [[monoclonal antibody]] that selectively binds with the interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory cytokines and chemokines.<br />
|PD=No formal pharmacodynamic studies have been conducted with TALTZ.<br />
|PK=bsorption<br />
<br />
Following a single subcutaneous dose of 160 mg in subjects with plaque psoriasis, ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.<br />
<br />
Steady-state concentrations were achieved by Week 8 following the 160 mg starting dose and 80 mg every 2 weeks dosing regimen; the mean ±SD steady-state trough concentration was 9.3 ±5.3 mcg/mL. Steady-state concentrations were achieved approximately 10 weeks after switching from the 80 mg every 2 weeks dosing regimen to the 80 mg every 4 weeks dosing regimen at Week 12. The mean ±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.<br />
<br />
In studies of subjects with plaque psoriasis, ixekizumab bioavailability ranged from 60% to 81% following subcutaneous injection. Administration of ixekizumab via injection in the thigh achieved a higher bioavailability relative to that achieved using other injection sites including the arm and abdomen.<br />
<br />
Distribution<br />
<br />
The mean (geometric CV%) volume of distribution at steady-state was 7.11 L (29%) in subjects with plaque psoriasis.<br />
<br />
Elimination<br />
<br />
The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 monoclonal antibody ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.<br />
<br />
The mean systemic clearance was 0.39 L/day (37%) and the mean (geometric CV%) half-life was 13 days (40%) in subjects with plaque psoriasis.<br />
<br />
Weight<br />
<br />
Ixekizumab clearance and volume of distribution increase as body weight increases.<br />
<br />
Dose Linearity<br />
<br />
Ixekizumab exhibited dose-proportional pharmacokinetics in subjects with plaque psoriasis over a dose range from 5 mg (not the recommended dose) to 160 mg following subcutaneous administration.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233417
Ixekizumab
2016-05-30T04:57:21Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-[[interleukin 17|interleukin-17]] [[monoclonal antibody]]<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque psoriasis]] who are candidates for systemic therapy or [[phototherapy]].<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%).<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Dosage=====<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
=====Tuberculosis Assessment Prior to Initiation of Ixekizumab=====<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
=====Important Administration Instructions=====<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
=====Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]=====<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions.<br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|useInPregnancyFDA=There are no available data on Ixekizumab use in pregnant women to inform any drug associated risks. Human [[IgG]] is known to cross the placental barrier; therefore, Ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.<br />
<br />
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.<br />
<br />
*Animal Data<br />
<br />
An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by [[subcutaneous injection]] during [[organogenesis]] to near [[parturition]] at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.<br />
<br />
In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly [[subcutaneous]] doses of ixekizumab up to 19 times the MRHD from the beginning of [[organogenesis]] to [[parturition]]. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or [[congenital defect]]. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.<br />
|useInNursing=There are no data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ixekizumab and any potential adverse effects on the breastfed infant from Ixekizumab or from the underlying maternal condition.<br />
|useInPed=The safety and effectiveness of Ixekizumab in pediatric patients (<18 years of age) have not been evaluated.<br />
|useInGeri=Of the 4204 [[psoriasis]] subjects exposed to Ixekizumab, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.<br />
|overdose=In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.<br />
|mechAction=Ixekizumab is a humanized IgG4 [[monoclonal antibody]] that selectively binds with the interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory cytokines and chemokines.<br />
|PD=No formal pharmacodynamic studies have been conducted with TALTZ.<br />
|PK=bsorption<br />
<br />
Following a single subcutaneous dose of 160 mg in subjects with plaque psoriasis, ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.<br />
<br />
Steady-state concentrations were achieved by Week 8 following the 160 mg starting dose and 80 mg every 2 weeks dosing regimen; the mean ±SD steady-state trough concentration was 9.3 ±5.3 mcg/mL. Steady-state concentrations were achieved approximately 10 weeks after switching from the 80 mg every 2 weeks dosing regimen to the 80 mg every 4 weeks dosing regimen at Week 12. The mean ±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.<br />
<br />
In studies of subjects with plaque psoriasis, ixekizumab bioavailability ranged from 60% to 81% following subcutaneous injection. Administration of ixekizumab via injection in the thigh achieved a higher bioavailability relative to that achieved using other injection sites including the arm and abdomen.<br />
<br />
Distribution<br />
<br />
The mean (geometric CV%) volume of distribution at steady-state was 7.11 L (29%) in subjects with plaque psoriasis.<br />
<br />
Elimination<br />
<br />
The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 monoclonal antibody ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.<br />
<br />
The mean systemic clearance was 0.39 L/day (37%) and the mean (geometric CV%) half-life was 13 days (40%) in subjects with plaque psoriasis.<br />
<br />
Weight<br />
<br />
Ixekizumab clearance and volume of distribution increase as body weight increases.<br />
<br />
Dose Linearity<br />
<br />
Ixekizumab exhibited dose-proportional pharmacokinetics in subjects with plaque psoriasis over a dose range from 5 mg (not the recommended dose) to 160 mg following subcutaneous administration.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233395
Ixekizumab
2016-05-26T05:48:59Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-interleukin-17 monoclonal antibody<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque psoriasis]] who are candidates for systemic therapy or [[phototherapy]].<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%).<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Dosage=====<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
=====Tuberculosis Assessment Prior to Initiation of Ixekizumab=====<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
=====Important Administration Instructions=====<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
=====Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]=====<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions.<br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|useInPregnancyFDA=There are no available data on Ixekizumab use in pregnant women to inform any drug associated risks. Human [[IgG]] is known to cross the placental barrier; therefore, Ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.<br />
<br />
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.<br />
<br />
*Animal Data<br />
<br />
An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by [[subcutaneous injection]] during [[organogenesis]] to near [[parturition]] at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.<br />
<br />
In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly [[subcutaneous]] doses of ixekizumab up to 19 times the MRHD from the beginning of [[organogenesis]] to [[parturition]]. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or [[congenital defect]]. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.<br />
|useInNursing=There are no data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ixekizumab and any potential adverse effects on the breastfed infant from Ixekizumab or from the underlying maternal condition.<br />
|useInPed=The safety and effectiveness of Ixekizumab in pediatric patients (<18 years of age) have not been evaluated.<br />
|useInGeri=Of the 4204 [[psoriasis]] subjects exposed to Ixekizumab, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.<br />
|overdose=In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.<br />
|mechAction=Ixekizumab is a humanized IgG4 [[monoclonal antibody]] that selectively binds with the interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory cytokines and chemokines.<br />
|PD=No formal pharmacodynamic studies have been conducted with TALTZ. <br />
|PK=bsorption<br />
<br />
Following a single subcutaneous dose of 160 mg in subjects with plaque psoriasis, ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.<br />
<br />
Steady-state concentrations were achieved by Week 8 following the 160 mg starting dose and 80 mg every 2 weeks dosing regimen; the mean ±SD steady-state trough concentration was 9.3 ±5.3 mcg/mL. Steady-state concentrations were achieved approximately 10 weeks after switching from the 80 mg every 2 weeks dosing regimen to the 80 mg every 4 weeks dosing regimen at Week 12. The mean ±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.<br />
<br />
In studies of subjects with plaque psoriasis, ixekizumab bioavailability ranged from 60% to 81% following subcutaneous injection. Administration of ixekizumab via injection in the thigh achieved a higher bioavailability relative to that achieved using other injection sites including the arm and abdomen.<br />
<br />
Distribution<br />
<br />
The mean (geometric CV%) volume of distribution at steady-state was 7.11 L (29%) in subjects with plaque psoriasis.<br />
<br />
Elimination<br />
<br />
The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 monoclonal antibody ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.<br />
<br />
The mean systemic clearance was 0.39 L/day (37%) and the mean (geometric CV%) half-life was 13 days (40%) in subjects with plaque psoriasis.<br />
<br />
Weight<br />
<br />
Ixekizumab clearance and volume of distribution increase as body weight increases.<br />
<br />
Dose Linearity<br />
<br />
Ixekizumab exhibited dose-proportional pharmacokinetics in subjects with plaque psoriasis over a dose range from 5 mg (not the recommended dose) to 160 mg following subcutaneous administration.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233394
Ixekizumab
2016-05-26T05:41:49Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-interleukin-17 monoclonal antibody<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque psoriasis]] who are candidates for systemic therapy or [[phototherapy]].<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%).<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Dosage=====<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
=====Tuberculosis Assessment Prior to Initiation of Ixekizumab=====<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
=====Important Administration Instructions=====<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
=====Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]=====<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions.<br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|useInPregnancyFDA=There are no available data on Ixekizumab use in pregnant women to inform any drug associated risks. Human [[IgG]] is known to cross the placental barrier; therefore, Ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus. When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.<br />
<br />
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.<br />
<br />
=====Animal Data=====<br />
<br />
An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly by [[subcutaneous injection]] during [[organogenesis]] to near [[parturition]] at doses up to 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.<br />
<br />
In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly [[subcutaneous]] doses of ixekizumab up to 19 times the MRHD from the beginning of [[organogenesis]] to [[parturition]]. Neonatal deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of 5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week). These neonatal deaths were attributed to early delivery, trauma, or [[congenital defect]]. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.<br />
|useInNursing=There are no data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ixekizumab and any potential adverse effects on the breastfed infant from Ixekizumab or from the underlying maternal condition. <br />
|useInPed=The safety and effectiveness of Ixekizumab in pediatric patients (<18 years of age) have not been evaluated. <br />
|useInGeri=Of the 4204 [[psoriasis]] subjects exposed to Ixekizumab, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233393
Ixekizumab
2016-05-26T05:32:45Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-interleukin-17 monoclonal antibody<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque psoriasis]] who are candidates for systemic therapy or [[phototherapy]].<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%).<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Dosage=====<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
=====Tuberculosis Assessment Prior to Initiation of Ixekizumab=====<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
=====Important Administration Instructions=====<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
=====Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]=====<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|postmarketing=FDA Package Insert for Ixekizumab contains no information regarding Adverse Reactions. <br />
|drugInteractions======Live Vaccinations=====<br />
<br />
Avoid use of live vaccines in patients treated with Ixekizumab.<br />
<br />
=====Cytochrome P450 Substrates=====<br />
<br />
The formation of [[cytochrome p450|CYP450 enzyme]]s can be altered by increased levels of certain [[cytokine]]s (e.g., [[IL-1]], [[IL-6]], [[IL-10]], [[TNF|TNFα]], [[IFN]]) during [[chronic inflammation]]. Thus, Ixekizumab, an antagonist of IL-17A, could normalize the formation of [[cytochrome p450|CYP450 enzyme]]s.<br />
<br />
Therefore, upon initiation or discontinuation of Ixekizumab in patients who are receiving concomitant drugs which are [[cytochrome p450|CYP450]] substrates, particularly those with a narrow [[therapeutic index]], consider monitoring for effect (e.g., for [[warfarin]]) or drug concentration (e.g., for [[cyclosporine]]) and consider dosage modification of the [[cytochrome p450|CYP450]] substrate.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233392
Ixekizumab
2016-05-26T05:20:43Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=[[User: Shankar Kumar |Shankar Kumar, M.B.B.S.]] [mailto:kumarshankar@wikidoc.org]]<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-interleukin-17 monoclonal antibody<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque psoriasis]] who are candidates for systemic therapy or [[phototherapy]].<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%).<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Dosage=====<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
=====Tuberculosis Assessment Prior to Initiation of Ixekizumab=====<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
=====Important Administration Instructions=====<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
=====Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]=====<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233391
Ixekizumab
2016-05-26T05:18:00Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-interleukin-17 monoclonal antibody<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque psoriasis]] who are candidates for systemic therapy or [[phototherapy]].<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%).<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Dosage=====<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
=====Tuberculosis Assessment Prior to Initiation of Ixekizumab=====<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
=====Important Administration Instructions=====<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
=====Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]=====<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*[[Infection]]s<br />
*[[Hypersensitivity reaction|Hypersensitivity Reaction]]s<br />
*[[Inflammatory Bowel Disease]]<br />
<br />
===Clinical Trials Experience===<br />
<br />
Because [[clinical trial]]s are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
====Weeks 0 to 12:====<br />
<br />
Three [[placebo]]-controlled trials in subjects with [[plaque psoriasis]] were integrated to evaluate the safety of Ixekizumab compared to [[placebo]] for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with [[plaque psoriasis]] received Ixekizumab (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of Ixekizumab (use up to 12 weeks) was also compared with an active comparator, U.S. approved [[etanercept]].<br />
<br />
In the 12-week, [[placebo]]-controlled period, adverse events occurred in 58% of the Ixekizumab Q2W group (2.5 per subject-year of follow-up) compared with 47% of the [[placebo]] group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the Ixekizumab group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the Ixekizumab group than in the [[placebo]] group during the 12-week [[placebo]]-controlled period of the pooled [[clinical trial]]s.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the Ixekizumab group and more frequently than in the [[placebo]] group during the 12-week induction period included [[rhinitis]], [[oral candidiasis]], [[urticaria]], [[influenza]], [[conjunctivitis]], [[inflammatory bowel disease]], and [[angioedema]].<br />
<br />
====Weeks 13 to 60:====<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of Ixekizumab 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with Ixekizumab (1.0 per subject-year of follow-up) compared to 58% of subjects treated with [[placebo]] (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with Ixekizumab (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
====Weeks 0 to 60:====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with Ixekizumab (1.4 per subject-year of follow-up) compared to 48% of subjects treated with [[placebo]] (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with Ixekizumab (0.06 per subject-year of follow-up), and in 2% of subjects treated with [[placebo]] (0.06 per subject-year of follow-up).<br />
<br />
====Specific Adverse Drug Reactions====<br />
<br />
=====Injection Site Reactions=====<br />
<br />
The most frequent injection site reactions were [[erythema]] and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of Ixekizumab.<br />
<br />
=====Infections=====<br />
<br />
In the 12-week, [[placebo]]-controlled period of the [[clinical trial]]s in [[plaque psoriasis]], infections occurred in 27% of subjects treated with Ixekizumab (1.2 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with Ixekizumab (0.70 per subject-year of follow-up) compared to 32% of subjects treated with [[placebo]] (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with Ixekizumab (0.01 per subject-year of follow-up) and none in the subjects treated with [[placebo]].<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with Ixekizumab (0.83 per subject-year of follow-up) compared to 23% of subjects treated with [[placebo]] (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with Ixekizumab (0.02 per subject-year of follow-up), and in 0.4% of subject treated with [[placebo]] (0.02 per subject-year of follow-up).<br />
<br />
=====Laboratory Assessment of Cytopenia=====<br />
<br />
*[[Neutropenia]]<br />
<br />
Over the entire treatment period (Weeks 0 to 60), [[neutropenia]] occurred in 11% of subjects treated with Ixekizumab (0.24 per subject-year of follow-up) compared to 3% of subjects treated with [[placebo]] (0.14 per subject-year of follow-up). In subjects treated with Ixekizumab, the incidence rate of [[neutropenia]] during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, [[placebo]]-controlled period, [[neutropenia]] ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the Ixekizumab group (0.007 per subject-year of follow-up) compared to 0.1% of the [[placebo]] group (0.006 per subject-year of follow-up). The majority of cases of [[neutropenia]] were either Grade 2 (2% for Ixekizumab 80 mg Q2W versus 0.3% for [[placebo]]; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for Ixekizumab 80 mg Q2W versus 3% for [[placebo]]; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). [[Neutropenia]] in the Ixekizumab group was not associated with an increased rate of infection compared to the [[placebo]] group.<br />
<br />
*[[Thrombocytopenia]]<br />
<br />
Ninety eight percent of cases of [[thrombocytopenia]] were Grade 1 (3% for Ixekizumab 80 mg Q2W versus 1% for [[placebo]]; ≥75,000 cells/mm3 to <150,000 cells/mm3). [[Thrombocytopenia]] in subjects treated with Ixekizumab was not associated with an increased rate of bleeding compared to subjects treated with [[placebo]].<br />
<br />
=====Active Comparator Trials=====<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved [[etanercept]] and 2% for Ixekizumab 80 mg Q2W. The incidence of infections was 18% for U.S. approved [[etanercept]] and 26% for Ixekizumab 80 mg Q2W. The rate of serious infections was 0.3% for both Ixekizumab 80 mg Q2W and U.S. approved [[etanercept]].<br />
<br />
===Immunogenicity===<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with Ixekizumab. By Week 12, approximately 9% of subjects treated with Ixekizumab every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with Ixekizumab at the recommended dosing regimen developed [[antibodies]] to ixekizumab during the 60-week treatment period. The clinical effects of [[antibodies]] to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with Ixekizumab at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Ixekizumab with the incidences of antibodies to other products may be misleading.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233390
Ixekizumab
2016-05-26T04:58:14Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-interleukin-17 monoclonal antibody<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe [[plaque psoriasis]] who are candidates for systemic therapy or [[phototherapy]].<br />
|adverseReactions=[[injection site reaction]]s, [[upper respiratory tract infection]]s, [[nausea]], and [[tinea]] infections (≥1%).<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Dosage=====<br />
Ixekizumab is administered by [[subcutaneous injection]]. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
<br />
=====Tuberculosis Assessment Prior to Initiation of Ixekizumab=====<br />
<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab.<br />
<br />
=====Important Administration Instructions=====<br />
<br />
There are two presentations for Ixekizumab (i.e., [[autoinjector]] and prefilled [[syringe]]).<br />
<br />
Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in [[subcutaneous injection]] technique using the [[autoinjector]] or prefilled [[syringe]]. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, [[erythema]]tous, [[induration|indurated]] or affected by [[psoriasis]]. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.<br />
<br />
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.<br />
<br />
=====Preparation for Use of Ixekizumab [[Autoinjector]] and Prefilled [[Syringe]]=====<br />
<br />
Before injection, remove Ixekizumab [[autoinjector]] or Ixekizumab prefilled [[syringe]] from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.<br />
<br />
Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the [[autoinjector]] or prefilled [[syringe]].<br />
<br />
Instruct patients using the [[autoinjector]] or prefilled [[syringe]] to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|fdaLIADPed=FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious [[hypersensitivity reaction]], such as [[anaphylaxis]], to ixekizumab or to any of the excipients.<br />
|warnings======Infections=====<br />
Ixekizumab may increase the risk of [[infection]]. In [[clinical trial]]s, the Ixekizumab treated group had a higher rate of infections than the [[placebo]] group (27% vs. 23%). [[Upper respiratory tract infection]]s, [[oral candidiasis]], [[conjunctivitis]] and [[tinea]] infections occurred more frequently in the Ixekizumab treated group than in the [[placebo]] group.<br />
<br />
Instruct patients treated with Ixekizumab to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue Ixekizumab until the infection resolves.<br />
<br />
=====Pre-treatment Evaluation for [[Tuberculosis]]=====<br />
Evaluate patients for [[tuberculosis]] (TB) infection prior to initiating treatment with Ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Ixekizumab. Consider [[tuberculosis medical therapy|anti-TB therapy]] prior to initiating Ixekizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
=====Hypersensitivity=====<br />
Serious [[hypersensitivity]] reactions, including [[angioedema]] and [[urticaria]] (each ≤0.1%), occurred in the Ixekizumab group in [[clinical trial]]s. If a serious [[hypersensitivity reaction]] occurs, discontinue Ixekizumab immediately and initiate appropriate therapy.<br />
<br />
=====Inflammatory Bowel Disease=====<br />
[[Crohn's disease]] and [[ulcerative colitis]], including exacerbations, occurred at a greater frequency in the Ixekizumab group ([[Crohn's disease]] 0.1%, [[ulcerative colitis]] 0.2%) than the [[placebo]] group (0%) during the 12-week, [[placebo]]-controlled period. During Ixekizumab treatment, monitor for onset or exacerbation of [[inflammatory bowel disease]].<br />
<br />
=====Immunizations=====<br />
Prior to initiating therapy with Ixekizumab, consider completion of all age appropriate [[immunization]]s according to current immunization guidelines. Avoid use of live [[vaccine]]s in patients treated with Ixekizumab. No data are available on the response to live or inactive [[vaccine]]s.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*Infections<br />
*Hypersensitivity Reactions<br />
*Inflammatory Bowel Disease<br />
<br />
Clinical Trials Experience<br />
<br />
Because clinical trials are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
==Weeks 0 to 12:==<br />
<br />
Three placebo-controlled trials in subjects with plaque psoriasis were integrated to evaluate the safety of TALTZ compared to placebo for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with plaque psoriasis received TALTZ (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of TALTZ (use up to 12 weeks) was also compared with an active comparator, U.S. approved etanercept.<br />
<br />
In the 12-week, placebo-controlled period, adverse events occurred in 58% of the TALTZ Q2W group (2.5 per subject-year of follow-up) compared with 47% of the placebo group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the TALTZ group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the TALTZ group than in the placebo group during the 12-week placebo-controlled period of the pooled clinical trials.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the TALTZ group and more frequently than in the placebo group during the 12-week induction period included rhinitis, oral candidiasis, urticaria, influenza, conjunctivitis, inflammatory bowel disease, and angioedema.<br />
<br />
==Weeks 13 to 60:==<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of TALTZ 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with TALTZ (1.0 per subject-year of follow-up) compared to 58% of subjects treated with placebo (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with TALTZ (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
==Weeks 0 to 60:==<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with TALTZ (1.4 per subject-year of follow-up) compared to 48% of subjects treated with placebo (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with TALTZ (0.06 per subject-year of follow-up), and in 2% of subjects treated with placebo (0.06 per subject-year of follow-up).<br />
<br />
==Specific Adverse Drug Reactions:==<br />
<br />
===Injection Site Reactions===<br />
<br />
The most frequent injection site reactions were erythema and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of TALTZ.<br />
<br />
===Infections===<br />
<br />
In the 12-week, placebo-controlled period of the clinical trials in plaque psoriasis, infections occurred in 27% of subjects treated with TALTZ (1.2 per subject-year of follow-up) compared to 23% of subjects treated with placebo (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with TALTZ (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with placebo (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with TALTZ (0.70 per subject-year of follow-up) compared to 32% of subjects treated with placebo (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with TALTZ (0.01 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with TALTZ (0.83 per subject-year of follow-up) compared to 23% of subjects treated with placebo (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with TALTZ (0.02 per subject-year of follow-up), and in 0.4% of subject treated with placebo (0.02 per subject-year of follow-up).<br />
<br />
===Laboratory Assessment of Cytopenia===<br />
<br />
====Neutropenia====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), neutropenia occurred in 11% of subjects treated with TALTZ (0.24 per subject-year of follow-up) compared to 3% of subjects treated with placebo (0.14 per subject-year of follow-up). In subjects treated with TALTZ, the incidence rate of neutropenia during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, placebo-controlled period, neutropenia ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the TALTZ group (0.007 per subject-year of follow-up) compared to 0.1% of the placebo group (0.006 per subject-year of follow-up). The majority of cases of neutropenia were either Grade 2 (2% for TALTZ 80 mg Q2W versus 0.3% for placebo; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for TALTZ 80 mg Q2W versus 3% for placebo; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). Neutropenia in the TALTZ group was not associated with an increased rate of infection compared to the placebo group.<br />
<br />
====Thrombocytopenia====<br />
<br />
Ninety eight percent of cases of thrombocytopenia were Grade 1 (3% for TALTZ 80 mg Q2W versus 1% for placebo; ≥75,000 cells/mm3 to <150,000 cells/mm3). Thrombocytopenia in subjects treated with TALTZ was not associated with an increased rate of bleeding compared to subjects treated with placebo.<br />
<br />
Active Comparator Trials<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved etanercept and 2% for TALTZ 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved etanercept and 2% for TALTZ 80 mg Q2W. The incidence of infections was 18% for U.S. approved etanercept and 26% for TALTZ 80 mg Q2W. The rate of serious infections was 0.3% for both TALTZ 80 mg Q2W and U.S. approved etanercept.<br />
<br />
==Immunogenicity==<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with TALTZ. By Week 12, approximately 9% of subjects treated with TALTZ every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with TALTZ at the recommended dosing regimen developed antibodies to ixekizumab during the 60-week treatment period. The clinical effects of antibodies to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with TALTZ at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to TALTZ with the incidences of antibodies to other products may be misleading.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233379
Ixekizumab
2016-05-25T09:00:08Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-interleukin-17 monoclonal antibody<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.<br />
|adverseReactions=injection site reactions, upper respiratory tract infections, nausea, and tinea infections (≥1%).<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult=*Administer by subcutaneous injection.<br />
*Recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious hypersensitivity reaction, such as anaphylaxis, to ixekizumab or to any of the excipients<br />
|warnings=*Infections<br />
<br />
:*TALTZ may increase the risk of infection. In clinical trials, the TALTZ group had a higher rate of infections than the placebo group (27% vs. 23%). Upper respiratory tract infections, oral candidiasis, conjunctivitis and tinea infections occurred more frequently in the TALTZ group than in the placebo group [see Adverse Reactions (6.1)].<br />
<br />
Instruct patients treated with TALTZ to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue TALTZ until the infection resolves.<br />
<br />
*Pre-treatment Evaluation for Tuberculosis<br />
:*Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with TALTZ. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering TALTZ. Consider anti-TB therapy prior to initiating TALTZ in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving TALTZ should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
*Hypersensitivity<br />
:*Serious hypersensitivity reactions, including angioedema and urticaria (each ≤0.1%), occurred in the TALTZ group in clinical trials. If a serious hypersensitivity reaction occurs, discontinue TALTZ immediately and initiate appropriate therapy [see Adverse Reactions (6.1)].<br />
<br />
*Inflammatory Bowel Disease<br />
:*Crohn's disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the TALTZ group (Crohn's disease 0.1%, ulcerative colitis 0.2%) than the placebo group (0%) during the 12-week, placebo-controlled period. During TALTZ treatment, monitor for onset or exacerbation of inflammatory bowel disease.<br />
<br />
*Immunizations<br />
:*Prior to initiating therapy with TALTZ, consider completion of all age appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with TALTZ. No data are available on the response to live or inactive vaccines.<br />
|clinicalTrials=The following adverse drug reactions are discussed in greater detail in other sections of the label:<br />
*Infections<br />
*Hypersensitivity Reactions<br />
*Inflammatory Bowel Disease<br />
<br />
Clinical Trials Experience<br />
<br />
Because clinical trials are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.<br />
<br />
==Weeks 0 to 12:==<br />
<br />
Three placebo-controlled trials in subjects with plaque psoriasis were integrated to evaluate the safety of TALTZ compared to placebo for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with plaque psoriasis received TALTZ (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of TALTZ (use up to 12 weeks) was also compared with an active comparator, U.S. approved etanercept.<br />
<br />
In the 12-week, placebo-controlled period, adverse events occurred in 58% of the TALTZ Q2W group (2.5 per subject-year of follow-up) compared with 47% of the placebo group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the TALTZ group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).<br />
<br />
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the TALTZ group than in the placebo group during the 12-week placebo-controlled period of the pooled clinical trials.<br />
<br />
Adverse reactions that occurred at rates less than 1% in the TALTZ group and more frequently than in the placebo group during the 12-week induction period included rhinitis, oral candidiasis, urticaria, influenza, conjunctivitis, inflammatory bowel disease, and angioedema.<br />
<br />
==Weeks 13 to 60:==<br />
<br />
A total of 332 subjects received the recommended maintenance regimen of TALTZ 80 mg dosed every 4 weeks.<br />
<br />
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with TALTZ (1.0 per subject-year of follow-up) compared to 58% of subjects treated with placebo (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with TALTZ (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
==Weeks 0 to 60:==<br />
<br />
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with TALTZ (1.4 per subject-year of follow-up) compared to 48% of subjects treated with placebo (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with TALTZ (0.06 per subject-year of follow-up), and in 2% of subjects treated with placebo (0.06 per subject-year of follow-up).<br />
<br />
==Specific Adverse Drug Reactions:==<br />
<br />
===Injection Site Reactions===<br />
<br />
The most frequent injection site reactions were erythema and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of TALTZ.<br />
<br />
===Infections===<br />
<br />
In the 12-week, placebo-controlled period of the clinical trials in plaque psoriasis, infections occurred in 27% of subjects treated with TALTZ (1.2 per subject-year of follow-up) compared to 23% of subjects treated with placebo (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with TALTZ (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with placebo (0.02 per subject-year of follow-up).<br />
<br />
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with TALTZ (0.70 per subject-year of follow-up) compared to 32% of subjects treated with placebo (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with TALTZ (0.01 per subject-year of follow-up) and none in the subjects treated with placebo.<br />
<br />
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with TALTZ (0.83 per subject-year of follow-up) compared to 23% of subjects treated with placebo (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with TALTZ (0.02 per subject-year of follow-up), and in 0.4% of subject treated with placebo (0.02 per subject-year of follow-up).<br />
<br />
===Laboratory Assessment of Cytopenia===<br />
<br />
====Neutropenia====<br />
<br />
Over the entire treatment period (Weeks 0 to 60), neutropenia occurred in 11% of subjects treated with TALTZ (0.24 per subject-year of follow-up) compared to 3% of subjects treated with placebo (0.14 per subject-year of follow-up). In subjects treated with TALTZ, the incidence rate of neutropenia during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.<br />
<br />
In the 12-week, placebo-controlled period, neutropenia ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the TALTZ group (0.007 per subject-year of follow-up) compared to 0.1% of the placebo group (0.006 per subject-year of follow-up). The majority of cases of neutropenia were either Grade 2 (2% for TALTZ 80 mg Q2W versus 0.3% for placebo; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for TALTZ 80 mg Q2W versus 3% for placebo; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). Neutropenia in the TALTZ group was not associated with an increased rate of infection compared to the placebo group.<br />
<br />
====Thrombocytopenia====<br />
<br />
Ninety eight percent of cases of thrombocytopenia were Grade 1 (3% for TALTZ 80 mg Q2W versus 1% for placebo; ≥75,000 cells/mm3 to <150,000 cells/mm3). Thrombocytopenia in subjects treated with TALTZ was not associated with an increased rate of bleeding compared to subjects treated with placebo.<br />
<br />
Active Comparator Trials<br />
<br />
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved etanercept and 2% for TALTZ 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved etanercept and 2% for TALTZ 80 mg Q2W. The incidence of infections was 18% for U.S. approved etanercept and 26% for TALTZ 80 mg Q2W. The rate of serious infections was 0.3% for both TALTZ 80 mg Q2W and U.S. approved etanercept.<br />
<br />
==Immunogenicity==<br />
<br />
As with all therapeutic proteins there is the potential for immunogenicity with TALTZ. By Week 12, approximately 9% of subjects treated with TALTZ every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with TALTZ at the recommended dosing regimen developed antibodies to ixekizumab during the 60-week treatment period. The clinical effects of antibodies to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.<br />
<br />
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with TALTZ at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.<br />
<br />
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.<br />
<br />
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to TALTZ with the incidences of antibodies to other products may be misleading.<br />
<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233378
Ixekizumab
2016-05-25T08:51:39Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=<!--Overview-->{{Shankar Kumar}}<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-interleukin-17 monoclonal antibody<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.<br />
|adverseReactions=injection site reactions, upper respiratory tract infections, nausea, and tinea infections (≥1%).<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult=*Administer by subcutaneous injection.<br />
*Recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious hypersensitivity reaction, such as anaphylaxis, to ixekizumab or to any of the excipients<br />
|warnings=*Infections<br />
<br />
:*TALTZ may increase the risk of infection. In clinical trials, the TALTZ group had a higher rate of infections than the placebo group (27% vs. 23%). Upper respiratory tract infections, oral candidiasis, conjunctivitis and tinea infections occurred more frequently in the TALTZ group than in the placebo group [see Adverse Reactions (6.1)].<br />
<br />
Instruct patients treated with TALTZ to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue TALTZ until the infection resolves.<br />
<br />
*Pre-treatment Evaluation for Tuberculosis<br />
:*Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with TALTZ. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering TALTZ. Consider anti-TB therapy prior to initiating TALTZ in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving TALTZ should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
*Hypersensitivity<br />
:*Serious hypersensitivity reactions, including angioedema and urticaria (each ≤0.1%), occurred in the TALTZ group in clinical trials. If a serious hypersensitivity reaction occurs, discontinue TALTZ immediately and initiate appropriate therapy [see Adverse Reactions (6.1)].<br />
<br />
*Inflammatory Bowel Disease<br />
:*Crohn's disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the TALTZ group (Crohn's disease 0.1%, ulcerative colitis 0.2%) than the placebo group (0%) during the 12-week, placebo-controlled period. During TALTZ treatment, monitor for onset or exacerbation of inflammatory bowel disease.<br />
<br />
*Immunizations<br />
:*Prior to initiating therapy with TALTZ, consider completion of all age appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with TALTZ. No data are available on the response to live or inactive vaccines.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Ixekizumab&diff=1233377
Ixekizumab
2016-05-25T08:50:24Z
<p>Shankar Kumar: Created page with "{{DrugProjectFormSinglePage |authorTag=<!--Overview-->{{SK}} |genericName=Ixekizumab |aOrAn=a |drugClass=humanized anti-interleukin-17 monoclonal antibody |indicationType=trea..."</p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag=<!--Overview-->{{SK}}<br />
|genericName=Ixekizumab<br />
|aOrAn=a<br />
|drugClass=humanized anti-interleukin-17 monoclonal antibody<br />
|indicationType=treatment<br />
|indication=of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.<br />
|adverseReactions=injection site reactions, upper respiratory tract infections, nausea, and tinea infections (≥1%).<br />
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b><br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult=*Administer by subcutaneous injection.<br />
*Recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.<br />
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in adult patients.<br />
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Ixekizumab in pediatric patients.<br />
|contraindications=Ixekizumab is contraindicated in patients with a previous serious hypersensitivity reaction, such as anaphylaxis, to ixekizumab or to any of the excipients <br />
|warnings=*Infections<br />
<br />
:*TALTZ may increase the risk of infection. In clinical trials, the TALTZ group had a higher rate of infections than the placebo group (27% vs. 23%). Upper respiratory tract infections, oral candidiasis, conjunctivitis and tinea infections occurred more frequently in the TALTZ group than in the placebo group [see Adverse Reactions (6.1)].<br />
<br />
Instruct patients treated with TALTZ to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue TALTZ until the infection resolves.<br />
<br />
*Pre-treatment Evaluation for Tuberculosis<br />
:*Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with TALTZ. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering TALTZ. Consider anti-TB therapy prior to initiating TALTZ in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving TALTZ should be monitored closely for signs and symptoms of active TB during and after treatment.<br />
<br />
*Hypersensitivity<br />
:*Serious hypersensitivity reactions, including angioedema and urticaria (each ≤0.1%), occurred in the TALTZ group in clinical trials. If a serious hypersensitivity reaction occurs, discontinue TALTZ immediately and initiate appropriate therapy [see Adverse Reactions (6.1)].<br />
<br />
*Inflammatory Bowel Disease<br />
:*Crohn's disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the TALTZ group (Crohn's disease 0.1%, ulcerative colitis 0.2%) than the placebo group (0%) during the 12-week, placebo-controlled period. During TALTZ treatment, monitor for onset or exacerbation of inflammatory bowel disease.<br />
<br />
*Immunizations<br />
:*Prior to initiating therapy with TALTZ, consider completion of all age appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with TALTZ. No data are available on the response to live or inactive vaccines.<br />
|alcohol=Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970621
Adenosine
2014-05-14T06:14:48Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.<br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=For rapid bolus [[intravenous]] use only.<br />
<br />
Adenosine [[injection]] should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a [[vein]] or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
*'''Adult Patients'''<br />
<br />
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous ([[CVP]] or other) administration of adenosine has not been systematically studied.<br />
<br />
Initial dose is given as a rapid [[intravenous]] bolus (administered over a 1 to 2 second period). If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, 12 mg should be given as a rapid [[intravenous]] bolus. This 12 mg dose may be repeated a second time if required.<br />
<br />
*'''Pediatric Patients'''<br />
<br />
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis. For pediatric patients with a body weight < 50 kg, an initial dose of 0.05 to 0.1 mg/kg as a rapid IV bolus is given either centrally or peripherally. A saline flush should follow. If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used. For [[pediatric]] patients with a body weight ≥ 50 kg, administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for adult and pediatric patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|monitoring======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|IVCompat=There is limited information about the compatibility of Adenosine and IV administrations.<br />
|overdose====Acute Overdose===<br />
The [[half-life]] of adenosine [[injection]] is less than 10 seconds. Thus, [[adverse effect]]s are generally rapidly self-limiting.<br />
====Management====<br />
Treatment of any prolonged [[adverse effect]]s should be individualized and be directed toward the specific effect. [[Methylxanthine]]s, such as [[caffeine]] and [[theophylline]], are [[competitive antagonist]]s of adenosine. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=Adenosine slows conduction time through the [[AV node|A-V node]], can interrupt the reentry pathways through the [[AV node|A-V node]], and can restore normal [[sinus rhythm]] in patients with [[paroxysmal supraventricular tachycardia]] ([[PSVT]]), including [[PSVT]] associated with [[WPW syndrome|Wolff-Parkinson-White Syndrome]].<br />
<br />
Adenosine is [[competitive antagonist|antagonized competitively]] by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]], and potentiated by blockers of [[nucleoside]] transport such as [[dipyridamole]]. Adenosine is not blocked by [[atropine]].<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=[[Intravenous]]ly administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by [[erythrocyte]]s and vascular [[endothelial cell]]s. This process involves a specific [[transmembrane]] [[nucleoside]] carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical. [[Intracellular]] adenosine is rapidly metabolized either via phosphorylation to [[adenosine monophosphate]] by [[adenosine kinase]], or via [[deamination]] to [[inosine]] by [[adenosine deaminase]] in the [[cytosol]]. Since [[adenosine kinase]] has a lower Km and Vmax than [[adenosine deaminase]], [[deamination]] plays a significant role only when [[cytosol]]ic adenosine saturates the [[phosphorylation]] pathway. [[Inosine]] formed by [[deamination]] of adenosine can leave the cell intact or can be degraded to [[hypoxanthine]], [[xanthine]], and ultimately [[uric acid]]. [[Adenosine monophosphate]] formed by [[phosphorylation]] of adenosine is incorporated into the high-energy [[phosphate]] pool. While [[extracellular]] adenosine is primarily cleared by cellular uptake with a [[half-life]] of less than 10 seconds in whole blood, excessive amounts may be [[deamination|deaminated]] by an ecto-form of [[adenosine deaminase]]. As adenosine requires no [[hepatic]] or [[renal]] function for its activation or inactivation, [[hepatic]] and [[renal]] failure would not be expected to alter its effectiveness or tolerability.<br />
|nonClinToxic=Studies in animals have not been performed to evaluate the [[carcinogenic]] potential of adenosine. Adenosine was negative for [[genotoxic]] potential in the [[Salmonella]] ([[Ames test|Ames Test]]) and Mammalian [[Microsome]] [[Assay]].<br />
<br />
Adenosine, however, like other [[nucleoside]]s at millimolar concentrations present for several doubling times of cells in [[culture]], is known to produce a variety of [[chromosomal]] alterations. [[Fertility]] studies in animals have not been conducted with adenosine.<br />
|clinicalStudies======Paroxysmal Supraventricular Tachycardia=====<br />
In controlled studies in the United States, bolus doses of 3, 6, 9, and 12 mg were studied. A cumulative 60% of patients with [[paroxysmal supraventricular tachycardia]] had converted to normal [[sinus rhythm]] within one minute after an [[intravenous]] bolus dose of 6 mg Adenosine (some converted on 3 mg and failures were given 6 mg), and a cumulative 92% converted after a bolus dose of 12 mg. Seven to sixteen percent of patients converted after 1-4 placebo bolus [[injection]]s. Similar responses were seen in a variety of patient subsets, including those using or not using [[digoxin]], those with [[WPW syndrome|Wolff-Parkinson-White Syndrome]], males, females, blacks, Caucasians, and Hispanics.<br />
<br />
Adenosine is not effective in converting rhythms other than [[PSVT]], such as [[atrial flutter]], [[atrial fibrillation]], or [[ventricular tachycardia]], to normal [[sinus rhythm]].<br />
|howSupplied=Adenosine [[injection]] is supplied as a [[sterile]], nonpyrogenic solution in [[normal saline]].<br />
<br />
'''NDC 10019-063-03 6 mg/2 mL''' (3 mg/mL) in 2 mL flip-top vials, packaged in shelf packs of ten.<br />
<br />
'''NDC 10019-063-08 6 mg/2 mL''' (3 mg/mL) in a 2 mL disposable glass [[syringe]], packaged in shelf packs of ten.<br />
|storage='''Store at 20°-25°C (68°-77°F), excursions permitted to 15°-30°C (59°-86°F). [See USP Controlled Room Temperature.]'''<br />
<br />
'''DO NOT REFRIGERATE''' as [[crystallization]] may occur. If crystallization has occurred, dissolve crystals by warming to room temperature. The solution must be clear at the time of use.<br />
<br />
Contains no preservatives. Discard unused portion.<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970620
Adenosine
2014-05-14T06:13:45Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.<br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=For rapid bolus [[intravenous]] use only.<br />
<br />
Adenosine [[injection]] should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a [[vein]] or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
*'''Adult Patients'''<br />
<br />
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous ([[CVP]] or other) administration of adenosine has not been systematically studied.<br />
<br />
Initial dose is given as a rapid [[intravenous]] bolus (administered over a 1 to 2 second period). If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, 12 mg should be given as a rapid [[intravenous]] bolus. This 12 mg dose may be repeated a second time if required.<br />
<br />
*'''Pediatric Patients'''<br />
<br />
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis. For pediatric patients with a body weight < 50 kg, an initial dose of 0.05 to 0.1 mg/kg as a rapid IV bolus is given either centrally or peripherally. A saline flush should follow. If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used. For [[pediatric]] patients with a body weight ≥ 50 kg, administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for adult and pediatric patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|monitoring======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|IVCompat=There is limited information about the compatibility of Adenosine and IV administrations.<br />
|overdose====Acute Overdose===<br />
The [[half-life]] of adenosine [[injection]] is less than 10 seconds. Thus, [[adverse effect]]s are generally rapidly self-limiting.<br />
====Management====<br />
Treatment of any prolonged [[adverse effect]]s should be individualized and be directed toward the specific effect. [[Methylxanthine]]s, such as [[caffeine]] and [[theophylline]], are [[competitive antagonist]]s of adenosine. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=Adenosine slows conduction time through the [[AV node|A-V node]], can interrupt the reentry pathways through the [[AV node|A-V node]], and can restore normal [[sinus rhythm]] in patients with [[paroxysmal supraventricular tachycardia]] ([[PSVT]]), including [[PSVT]] associated with [[WPW syndrome|Wolff-Parkinson-White Syndrome]].<br />
<br />
Adenosine is [[competitive antagonist|antagonized competitively]] by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]], and potentiated by blockers of [[nucleoside]] transport such as [[dipyridamole]]. Adenosine is not blocked by [[atropine]].<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=[[Intravenous]]ly administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by [[erythrocyte]]s and vascular [[endothelial cell]]s. This process involves a specific [[transmembrane]] [[nucleoside]] carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical. [[Intracellular]] adenosine is rapidly metabolized either via phosphorylation to [[adenosine monophosphate]] by [[adenosine kinase]], or via [[deamination]] to [[inosine]] by [[adenosine deaminase]] in the [[cytosol]]. Since [[adenosine kinase]] has a lower Km and Vmax than [[adenosine deaminase]], [[deamination]] plays a significant role only when [[cytosol]]ic adenosine saturates the [[phosphorylation]] pathway. [[Inosine]] formed by [[deamination]] of adenosine can leave the cell intact or can be degraded to [[hypoxanthine]], [[xanthine]], and ultimately [[uric acid]]. [[Adenosine monophosphate]] formed by [[phosphorylation]] of adenosine is incorporated into the high-energy [[phosphate]] pool. While [[extracellular]] adenosine is primarily cleared by cellular uptake with a [[half-life]] of less than 10 seconds in whole blood, excessive amounts may be [[deamination|deaminated]] by an ecto-form of [[adenosine deaminase]]. As adenosine requires no [[hepatic]] or [[renal]] function for its activation or inactivation, [[hepatic]] and [[renal]] failure would not be expected to alter its effectiveness or tolerability.<br />
|nonClinToxic=Studies in animals have not been performed to evaluate the [[carcinogenic]] potential of adenosine. Adenosine was negative for [[genotoxic]] potential in the [[Salmonella]] ([[Ames test|Ames Test]]) and Mammalian [[Microsome]] [[Assay]].<br />
<br />
Adenosine, however, like other [[nucleoside]]s at millimolar concentrations present for several doubling times of cells in [[culture]], is known to produce a variety of [[chromosomal]] alterations. [[Fertility]] studies in animals have not been conducted with adenosine.<br />
|clinicalStudies======Paroxysmal Supraventricular Tachycardia=====<br />
In controlled studies in the United States, bolus doses of 3, 6, 9, and 12 mg were studied. A cumulative 60% of patients with [[paroxysmal supraventricular tachycardia]] had converted to normal [[sinus rhythm]] within one minute after an [[intravenous]] bolus dose of 6 mg Adenosine (some converted on 3 mg and failures were given 6 mg), and a cumulative 92% converted after a bolus dose of 12 mg. Seven to sixteen percent of patients converted after 1-4 placebo bolus [[injection]]s. Similar responses were seen in a variety of patient subsets, including those using or not using [[digoxin]], those with [[WPW syndrome|Wolff-Parkinson-White Syndrome]], males, females, blacks, Caucasians, and Hispanics.<br />
<br />
Adenosine is not effective in converting rhythms other than [[PSVT]], such as [[atrial flutter]], [[atrial fibrillation]], or [[ventricular tachycardia]], to normal [[sinus rhythm]].<br />
|howSupplied=Adenosine [[injection]] is supplied as a [[sterile]], non[[pyrogenic]] solution in [[normal saline]].<br />
<br />
'''NDC 10019-063-03 6 mg/2 mL''' (3 mg/mL) in 2 mL flip-top vials, packaged in shelf packs of ten.<br />
<br />
'''NDC 10019-063-08 6 mg/2 mL''' (3 mg/mL) in a 2 mL disposable glass [[syringe]], packaged in shelf packs of ten.<br />
|storage='''Store at 20°-25°C (68°-77°F), excursions permitted to 15°-30°C (59°-86°F). [See USP Controlled Room Temperature.]'''<br />
<br />
'''DO NOT REFRIGERATE''' as [[crystallization]] may occur. If crystallization has occurred, dissolve crystals by warming to room temperature. The solution must be clear at the time of use.<br />
<br />
Contains no preservatives. Discard unused portion.<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970619
Adenosine
2014-05-14T06:10:28Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.<br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=For rapid bolus [[intravenous]] use only.<br />
<br />
Adenosine [[injection]] should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a [[vein]] or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
*'''Adult Patients'''<br />
<br />
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous ([[CVP]] or other) administration of adenosine has not been systematically studied.<br />
<br />
Initial dose is given as a rapid [[intravenous]] bolus (administered over a 1 to 2 second period). If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, 12 mg should be given as a rapid [[intravenous]] bolus. This 12 mg dose may be repeated a second time if required.<br />
<br />
*'''Pediatric Patients'''<br />
<br />
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis. For pediatric patients with a body weight < 50 kg, an initial dose of 0.05 to 0.1 mg/kg as a rapid IV bolus is given either centrally or peripherally. A saline flush should follow. If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used. For [[pediatric]] patients with a body weight ≥ 50 kg, administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for adult and pediatric patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|monitoring======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|IVCompat=There is limited information about the compatibility of Adenosine and IV administrations.<br />
|overdose====Acute Overdose===<br />
The [[half-life]] of adenosine [[injection]] is less than 10 seconds. Thus, [[adverse effect]]s are generally rapidly self-limiting.<br />
====Management====<br />
Treatment of any prolonged [[adverse effect]]s should be individualized and be directed toward the specific effect. [[Methylxanthine]]s, such as [[caffeine]] and [[theophylline]], are [[competitive antagonist]]s of adenosine. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=Adenosine slows conduction time through the [[AV node|A-V node]], can interrupt the reentry pathways through the [[AV node|A-V node]], and can restore normal [[sinus rhythm]] in patients with [[paroxysmal supraventricular tachycardia]] ([[PSVT]]), including [[PSVT]] associated with [[WPW syndrome|Wolff-Parkinson-White Syndrome]].<br />
<br />
Adenosine is [[competitive antagonist|antagonized competitively]] by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]], and potentiated by blockers of [[nucleoside]] transport such as [[dipyridamole]]. Adenosine is not blocked by [[atropine]].<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=[[Intravenous]]ly administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by [[erythrocyte]]s and vascular [[endothelial cell]]s. This process involves a specific [[transmembrane]] [[nucleoside]] carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical. [[Intracellular]] adenosine is rapidly metabolized either via phosphorylation to [[adenosine monophosphate]] by [[adenosine kinase]], or via [[deamination]] to [[inosine]] by [[adenosine deaminase]] in the [[cytosol]]. Since [[adenosine kinase]] has a lower Km and Vmax than [[adenosine deaminase]], [[deamination]] plays a significant role only when [[cytosol]]ic adenosine saturates the [[phosphorylation]] pathway. [[Inosine]] formed by [[deamination]] of adenosine can leave the cell intact or can be degraded to [[hypoxanthine]], [[xanthine]], and ultimately [[uric acid]]. [[Adenosine monophosphate]] formed by [[phosphorylation]] of adenosine is incorporated into the high-energy [[phosphate]] pool. While [[extracellular]] adenosine is primarily cleared by cellular uptake with a [[half-life]] of less than 10 seconds in whole blood, excessive amounts may be [[deamination|deaminated]] by an ecto-form of [[adenosine deaminase]]. As adenosine requires no [[hepatic]] or [[renal]] function for its activation or inactivation, [[hepatic]] and [[renal]] failure would not be expected to alter its effectiveness or tolerability.<br />
|nonClinToxic=Studies in animals have not been performed to evaluate the [[carcinogenic]] potential of adenosine. Adenosine was negative for [[genotoxic]] potential in the [[Salmonella]] ([[Ames test|Ames Test]]) and Mammalian [[Microsome]] [[Assay]].<br />
<br />
Adenosine, however, like other [[nucleoside]]s at millimolar concentrations present for several doubling times of cells in [[culture]], is known to produce a variety of [[chromosomal]] alterations. [[Fertility]] studies in animals have not been conducted with adenosine.<br />
|clinicalStudies======Paroxysmal Supraventricular Tachycardia=====<br />
In controlled studies in the United States, bolus doses of 3, 6, 9, and 12 mg were studied. A cumulative 60% of patients with [[paroxysmal supraventricular tachycardia]] had converted to normal [[sinus rhythm]] within one minute after an [[intravenous]] bolus dose of 6 mg Adenosine (some converted on 3 mg and failures were given 6 mg), and a cumulative 92% converted after a bolus dose of 12 mg. Seven to sixteen percent of patients converted after 1-4 placebo bolus [[injection]]s. Similar responses were seen in a variety of patient subsets, including those using or not using [[digoxin]], those with [[WPW syndrome|Wolff-Parkinson-White Syndrome]], males, females, blacks, Caucasians, and Hispanics.<br />
<br />
Adenosine is not effective in converting rhythms other than [[PSVT]], such as [[atrial flutter]], [[atrial fibrillation]], or [[ventricular tachycardia]], to normal [[sinus rhythm]].<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970618
Adenosine
2014-05-14T06:09:09Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.<br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=For rapid bolus [[intravenous]] use only.<br />
<br />
Adenosine [[injection]] should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a [[vein]] or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
*'''Adult Patients'''<br />
<br />
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous ([[CVP]] or other) administration of adenosine has not been systematically studied.<br />
<br />
Initial dose is given as a rapid [[intravenous]] bolus (administered over a 1 to 2 second period). If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, 12 mg should be given as a rapid [[intravenous]] bolus. This 12 mg dose may be repeated a second time if required.<br />
<br />
*'''Pediatric Patients'''<br />
<br />
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis. For pediatric patients with a body weight < 50 kg, an initial dose of 0.05 to 0.1 mg/kg as a rapid IV bolus is given either centrally or peripherally. A saline flush should follow. If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used. For [[pediatric]] patients with a body weight ≥ 50 kg, administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for adult and pediatric patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|monitoring======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|IVCompat=There is limited information about the compatibility of Adenosine and IV administrations.<br />
|overdose====Acute Overdose===<br />
The [[half-life]] of adenosine [[injection]] is less than 10 seconds. Thus, [[adverse effect]]s are generally rapidly self-limiting.<br />
====Management====<br />
Treatment of any prolonged [[adverse effect]]s should be individualized and be directed toward the specific effect. [[Methylxanthine]]s, such as [[caffeine]] and [[theophylline]], are [[competitive antagonist]]s of adenosine. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=Adenosine slows conduction time through the [[AV node|A-V node]], can interrupt the reentry pathways through the [[AV node|A-V node]], and can restore normal [[sinus rhythm]] in patients with [[paroxysmal supraventricular tachycardia]] ([[PSVT]]), including [[PSVT]] associated with [[WPW syndrome|Wolff-Parkinson-White Syndrome]].<br />
<br />
Adenosine is [[competitive antagonist|antagonized competitively]] by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]], and potentiated by blockers of [[nucleoside]] transport such as [[dipyridamole]]. Adenosine is not blocked by [[atropine]].<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=[[Intravenous]]ly administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by [[erythrocyte]]s and vascular [[endothelial cell]]s. This process involves a specific [[transmembrane]] [[nucleoside]] carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical. [[Intracellular]] adenosine is rapidly metabolized either via phosphorylation to [[adenosine monophosphate]] by [[adenosine kinase]], or via [[deamination]] to [[inosine]] by [[adenosine deaminase]] in the [[cytosol]]. Since [[adenosine kinase]] has a lower Km and Vmax than [[adenosine deaminase]], [[deamination]] plays a significant role only when [[cytosol]]ic adenosine saturates the [[phosphorylation]] pathway. [[Inosine]] formed by [[deamination]] of adenosine can leave the cell intact or can be degraded to [[hypoxanthine]], [[xanthine]], and ultimately [[uric acid]]. [[Adenosine monophosphate]] formed by [[phosphorylation]] of adenosine is incorporated into the high-energy [[phosphate]] pool. While [[extracellular]] adenosine is primarily cleared by cellular uptake with a [[half-life]] of less than 10 seconds in whole blood, excessive amounts may be [[deamination|deaminated]] by an ecto-form of [[adenosine deaminase]]. As adenosine requires no [[hepatic]] or [[renal]] function for its activation or inactivation, [[hepatic]] and [[renal]] failure would not be expected to alter its effectiveness or tolerability.<br />
|nonClinToxic=Studies in animals have not been performed to evaluate the [[carcinogenic]] potential of adenosine. Adenosine was negative for [[genotoxic]] potential in the [[Salmonella]] ([[Ames test|Ames Test]]) and Mammalian [[Microsmal assay|Microsome Assay]].<br />
<br />
Adenosine, however, like other [[nucleoside]]s at millimolar concentrations present for several doubling times of cells in [[culture]], is known to produce a variety of [[chromosomal]] alterations. [[Fertility]] studies in animals have not been conducted with adenosine.<br />
|clinicalStudies======Paroxysmal Supraventricular Tachycardia=====<br />
In controlled studies in the United States, bolus doses of 3, 6, 9, and 12 mg were studied. A cumulative 60% of patients with [[paroxysmal supraventricular tachycardia]] had converted to normal [[sinus rhythm]] within one minute after an [[intravenous]] bolus dose of 6 mg Adenosine (some converted on 3 mg and failures were given 6 mg), and a cumulative 92% converted after a bolus dose of 12 mg. Seven to sixteen percent of patients converted after 1-4 placebo bolus [[injection]]s. Similar responses were seen in a variety of patient subsets, including those using or not using [[digoxin]], those with [[WPW syndrome|Wolff-Parkinson-White Syndrome]], males, females, blacks, Caucasians, and Hispanics.<br />
<br />
Adenosine is not effective in converting rhythms other than [[PSVT]], such as [[atrial flutter]], [[atrial fibrillation]], or [[ventricular tachycardia]], to normal [[sinus rhythm]].<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970617
Adenosine
2014-05-14T06:07:47Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.<br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=For rapid bolus [[intravenous]] use only.<br />
<br />
Adenosine [[injection]] should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a [[vein]] or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
*'''Adult Patients'''<br />
<br />
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous ([[CVP]] or other) administration of adenosine has not been systematically studied.<br />
<br />
Initial dose is given as a rapid [[intravenous]] bolus (administered over a 1 to 2 second period). If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, 12 mg should be given as a rapid [[intravenous]] bolus. This 12 mg dose may be repeated a second time if required.<br />
<br />
*'''Pediatric Patients'''<br />
<br />
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis. For pediatric patients with a body weight < 50 kg, an initial dose of 0.05 to 0.1 mg/kg as a rapid IV bolus is given either centrally or peripherally. A saline flush should follow. If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used. For [[pediatric]] patients with a body weight ≥ 50 kg, administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for adult and pediatric patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|monitoring======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|IVCompat=There is limited information about the compatibility of Adenosine and IV administrations.<br />
|overdose====Acute Overdose===<br />
The [[half-life]] of adenosine [[injection]] is less than 10 seconds. Thus, [[adverse effect]]s are generally rapidly self-limiting.<br />
====Management====<br />
Treatment of any prolonged [[adverse effect]]s should be individualized and be directed toward the specific effect. [[Methylxanthine]]s, such as [[caffeine]] and [[theophylline]], are [[competitive antagonist]]s of adenosine. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=Adenosine slows conduction time through the [[AV node|A-V node]], can interrupt the reentry pathways through the [[AV node|A-V node]], and can restore normal [[sinus rhythm]] in patients with [[paroxysmal supraventricular tachycardia]] ([[PSVT]]), including [[PSVT]] associated with [[WPW syndrome|Wolff-Parkinson-White Syndrome]].<br />
<br />
Adenosine is [[competitive antagonist|antagonized competitively]] by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]], and potentiated by blockers of [[nucleoside]] transport such as [[dipyridamole]]. Adenosine is not blocked by [[atropine]].<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=[[Intravenous]]ly administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by [[erythrocyte]]s and vascular [[endothelial cell]]s. This process involves a specific [[transmembrane]] [[nucleoside]] carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical. [[Intracellular]] adenosine is rapidly metabolized either via phosphorylation to [[adenosine monophosphate]] by [[adenosine kinase]], or via [[deamination]] to [[inosine]] by [[adenosine deaminase]] in the [[cytosol]]. Since [[adenosine kinase]] has a lower Km and Vmax than [[adenosine deaminase]], [[deamination]] plays a significant role only when [[cytosol]]ic adenosine saturates the [[phosphorylation]] pathway. [[Inosine]] formed by [[deamination]] of adenosine can leave the cell intact or can be degraded to [[hypoxanthine]], [[xanthine]], and ultimately [[uric acid]]. [[Adenosine monophosphate]] formed by [[phosphorylation]] of adenosine is incorporated into the high-energy [[phosphate]] pool. While [[extracellular]] adenosine is primarily cleared by cellular uptake with a [[half-life]] of less than 10 seconds in whole blood, excessive amounts may be [[deamination|deaminated]] by an ecto-form of [[adenosine deaminase]]. As adenosine requires no [[hepatic]] or [[renal]] function for its activation or inactivation, [[hepatic]] and [[renal]] failure would not be expected to alter its effectiveness or tolerability.<br />
|nonClinToxic=Studies in animals have not been performed to evaluate the carcinogenic potential of adenosine. Adenosine was negative for [[genotoxic]] potential in the [[Salmonella]] ([[Ames test|Ames Test]]) and Mammalian [[|Microsmal assay|Microsome Assay]].<br />
<br />
Adenosine, however, like other [[nucleoside]]s at millimolar concentrations present for several doubling times of cells in culture, is known to produce a variety of [[chromosomal]] alterations. [[Fertility]] studies in animals have not been conducted with adenosine.<br />
|clinicalStudies======Paroxysmal Supraventricular Tachycardia=====<br />
In controlled studies in the United States, bolus doses of 3, 6, 9, and 12 mg were studied. A cumulative 60% of patients with [[paroxysmal supraventricular tachycardia]] had converted to normal [[sinus rhythm]] within one minute after an [[intravenous]] bolus dose of 6 mg Adenosine (some converted on 3 mg and failures were given 6 mg), and a cumulative 92% converted after a bolus dose of 12 mg. Seven to sixteen percent of patients converted after 1-4 placebo bolus [[injection]]s. Similar responses were seen in a variety of patient subsets, including those using or not using [[digoxin]], those with [[WPW syndrome|Wolff-Parkinson-White Syndrome]], males, females, blacks, Caucasians, and Hispanics.<br />
<br />
Adenosine is not effective in converting rhythms other than [[PSVT]], such as [[atrial flutter]], [[atrial fibrillation]], or [[ventricular tachycardia]], to normal [[sinus rhythm]].<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970616
Adenosine
2014-05-14T06:03:34Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.<br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=For rapid bolus [[intravenous]] use only.<br />
<br />
Adenosine [[injection]] should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a [[vein]] or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
*'''Adult Patients'''<br />
<br />
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous ([[CVP]] or other) administration of adenosine has not been systematically studied.<br />
<br />
Initial dose is given as a rapid [[intravenous]] bolus (administered over a 1 to 2 second period). If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, 12 mg should be given as a rapid [[intravenous]] bolus. This 12 mg dose may be repeated a second time if required.<br />
<br />
*'''Pediatric Patients'''<br />
<br />
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis. For pediatric patients with a body weight < 50 kg, an initial dose of 0.05 to 0.1 mg/kg as a rapid IV bolus is given either centrally or peripherally. A saline flush should follow. If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used. For [[pediatric]] patients with a body weight ≥ 50 kg, administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for adult and pediatric patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|monitoring======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|IVCompat=There is limited information about the compatibility of Adenosine and IV administrations.<br />
|overdose====Acute Overdose===<br />
The [[half-life]] of adenosine [[injection]] is less than 10 seconds. Thus, [[adverse effect]]s are generally rapidly self-limiting.<br />
====Management====<br />
Treatment of any prolonged [[adverse effect]]s should be individualized and be directed toward the specific effect. [[Methylxanthine]]s, such as [[caffeine]] and [[theophylline]], are [[competitive antagonist]]s of adenosine. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=Adenosine slows conduction time through the [[AV node|A-V node]], can interrupt the reentry pathways through the [[AV node|A-V node]], and can restore normal [[sinus rhythm]] in patients with [[paroxysmal supraventricular tachycardia]] ([[PSVT]]), including [[PSVT]] associated with [[WPW syndrome|Wolff-Parkinson-White Syndrome]].<br />
<br />
Adenosine is [[competitive antagonist|antagonized competitively]] by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]], and potentiated by blockers of [[nucleoside]] transport such as [[dipyridamole]]. Adenosine is not blocked by [[atropine]].<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=[[Intravenous]]ly administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by [[erythrocyte]]s and vascular [[endothelial cell]]s. This process involves a specific [[transmembrane]] [[nucleoside]] carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical. [[Intracellular]] adenosine is rapidly metabolized either via phosphorylation to [[adenosine monophosphate]] by [[adenosine kinase]], or via [[deamination]] to [[inosine]] by [[adenosine deaminase]] in the [[cytosol]]. Since [[adenosine kinase]] has a lower Km and Vmax than [[adenosine deaminase]], [[deamination]] plays a significant role only when [[cytosol]]ic adenosine saturates the [[phosphorylation]] pathway. [[Inosine]] formed by [[deamination]] of adenosine can leave the cell intact or can be degraded to [[hypoxanthine]], [[xanthine]], and ultimately [[uric acid]]. [[Adenosine monophosphate]] formed by [[phosphorylation]] of adenosine is incorporated into the high-energy [[phosphate]] pool. While [[extracellular]] adenosine is primarily cleared by cellular uptake with a [[half-life]] of less than 10 seconds in whole blood, excessive amounts may be [[deamination|deaminated]] by an ecto-form of [[adenosine deaminase]]. As adenosine requires no [[hepatic]] or [[renal]] function for its activation or inactivation, [[hepatic]] and [[renal]] failure would not be expected to alter its effectiveness or tolerability.<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Paroxysmal Supraventricular Tachycardia=====<br />
In controlled studies in the United States, bolus doses of 3, 6, 9, and 12 mg were studied. A cumulative 60% of patients with [[paroxysmal supraventricular tachycardia]] had converted to normal [[sinus rhythm]] within one minute after an [[intravenous]] bolus dose of 6 mg Adenosine (some converted on 3 mg and failures were given 6 mg), and a cumulative 92% converted after a bolus dose of 12 mg. Seven to sixteen percent of patients converted after 1-4 placebo bolus [[injection]]s. Similar responses were seen in a variety of patient subsets, including those using or not using [[digoxin]], those with [[WPW syndrome|Wolff-Parkinson-White Syndrome]], males, females, blacks, Caucasians, and Hispanics.<br />
<br />
Adenosine is not effective in converting rhythms other than [[PSVT]], such as [[atrial flutter]], [[atrial fibrillation]], or [[ventricular tachycardia]], to normal [[sinus rhythm]].<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970615
Adenosine
2014-05-14T05:40:26Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.<br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=For rapid bolus [[intravenous]] use only.<br />
<br />
Adenosine [[injection]] should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a [[vein]] or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
*'''Adult Patients'''<br />
<br />
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous ([[CVP]] or other) administration of adenosine has not been systematically studied.<br />
<br />
Initial dose is given as a rapid [[intravenous]] bolus (administered over a 1 to 2 second period). If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, 12 mg should be given as a rapid [[intravenous]] bolus. This 12 mg dose may be repeated a second time if required.<br />
<br />
*'''Pediatric Patients'''<br />
<br />
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis. For pediatric patients with a body weight < 50 kg, an initial dose of 0.05 to 0.1 mg/kg as a rapid IV bolus is given either centrally or peripherally. A saline flush should follow. If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used. For [[pediatric]] patients with a body weight ≥ 50 kg, administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for adult and pediatric patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|monitoring======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|IVCompat=There is limited information about the compatibility of Adenosine and IV administrations.<br />
|overdose====Acute Overdose===<br />
The [[half-life]] of adenosine [[injection]] is less than 10 seconds. Thus, [[adverse effect]]s are generally rapidly self-limiting.<br />
====Management====<br />
Treatment of any prolonged [[adverse effect]]s should be individualized and be directed toward the specific effect. [[Methylxanthine]]s, such as [[caffeine]] and [[theophylline]], are [[competitive antagonist]]s of adenosine. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=Adenosine slows conduction time through the [[AV node|A-V node]], can interrupt the reentry pathways through the [[AV node|A-V node]], and can restore normal [[sinus rhythm]] in patients with [[paroxysmal supraventricular tachycardia]] ([[PSVT]]), including [[PSVT]] associated with [[WPW syndrome|Wolff-Parkinson-White Syndrome]].<br />
<br />
Adenosine is [[competitive antagonist|antagonized competitively]] by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]], and potentiated by blockers of [[nucleoside]] transport such as [[dipyridamole]]. Adenosine is not blocked by [[atropine]].<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=[[Intravenous]]ly administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by [[erythrocyte]]s and vascular [[endothelial cell]]s. This process involves a specific [[transmembrane]] [[nucleoside]] carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical. [[Intracellular]] adenosine is rapidly metabolized either via phosphorylation to [[adenosine monophosphate]] by [[adenosine kinase]], or via [[deamination]] to [[inosine]] by [[adenosine deaminase]] in the [[cytosol]]. Since [[adenosine kinase]] has a lower Km and Vmax than [[adenosine deaminase]], [[deamination]] plays a significant role only when [[cytosol]]ic adenosine saturates the [[phosphorylation]] pathway. [[Inosine]] formed by [[deamination]] of adenosine can leave the cell intact or can be degraded to [[hypoxanthine]], [[xanthine]], and ultimately [[uric acid]]. [[Adenosine monophosphate]] formed by [[phosphorylation]] of adenosine is incorporated into the high-energy [[phosphate]] pool. While [[extracellular]] adenosine is primarily cleared by cellular uptake with a [[half-life]] of less than 10 seconds in whole blood, excessive amounts may be [[deamination|deaminated]] by an ecto-form of [[adenosine deaminase]]. As adenosine requires no [[hepatic]] or [[renal]] function for its activation or inactivation, [[hepatic]] and [[renal]] failure would not be expected to alter its effectiveness or tolerability.<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970614
Adenosine
2014-05-14T05:39:03Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.<br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=For rapid bolus [[intravenous]] use only.<br />
<br />
Adenosine [[injection]] should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a [[vein]] or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
*'''Adult Patients'''<br />
<br />
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous ([[CVP]] or other) administration of adenosine has not been systematically studied.<br />
<br />
Initial dose is given as a rapid [[intravenous]] bolus (administered over a 1 to 2 second period). If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, 12 mg should be given as a rapid [[intravenous]] bolus. This 12 mg dose may be repeated a second time if required.<br />
<br />
*'''Pediatric Patients'''<br />
<br />
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis. For pediatric patients with a body weight < 50 kg, an initial dose of 0.05 to 0.1 mg/kg as a rapid IV bolus is given either centrally or peripherally. A saline flush should follow. If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used. For [[pediatric]] patients with a body weight ≥ 50 kg, administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for adult and pediatric patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|monitoring======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|IVCompat=There is limited information about the compatibility of Adenosine and IV administrations.<br />
|overdose====Acute Overdose===<br />
The [[half-life]] of adenosine [[injection]] is less than 10 seconds. Thus, [[adverse effect]]s are generally rapidly self-limiting.<br />
====Management====<br />
Treatment of any prolonged [[adverse effect]]s should be individualized and be directed toward the specific effect. [[Methylxanthine]]s, such as [[caffeine]] and [[theophylline]], are [[competitive antagonist]]s of adenosine. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=Adenosine slows conduction time through the [[AV node|A-V node]], can interrupt the reentry pathways through the [[AV node|A-V node]], and can restore normal [[sinus rhythm]] in patients with [[paroxysmal supraventricular tachycardia]] ([[PSVT]]), including [[PSVT]] associated with [[WPW syndrome|Wolff-Parkinson-White Syndrome]].<br />
<br />
Adenosine is [[competitive antagonist|antagonized competitively]] by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]], and potentiated by blockers of [[nucleoside]] transport such as [[dipyridamole]]. Adenosine is not blocked by [[atropine]].<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=[[Intravenous]]ly administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by [[erythrocyte]]s and vascular [[endothelial cell]]s. This process involves a specific [[transmembrane]] [[nucleoside]] carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical. [[Intracellular]] adenosine is rapidly metabolized either via phosphorylation to [[adenosine monophosphate]] by [[adenosine kinase]], or via [[deamination]] to [[inosine]] by [[adenosine deaminase]] in the [[cytosol]]. Since [[adenosine kinase]] has a lower [[Km]] and [[Vmax]] than [[adenosine deaminase]], [[deamination]] plays a significant role only when [[cytosol]]ic adenosine saturates the [[phosphorylation]] pathway. [[Inosine]] formed by [[deamination]] of adenosine can leave the cell intact or can be degraded to [[hypoxanthine]], [[xanthine]], and ultimately [[uric acid]]. [[Adenosine monophosphate]] formed by [[phosphorylation]] of adenosine is incorporated into the high-energy [[phosphate]] pool. While [[extracellular]] adenosine is primarily cleared by cellular uptake with a [[half-life]] of less than 10 seconds in whole blood, excessive amounts may be [[deamination|deaminated]] by an ecto-form of [[adenosine deaminase]]. As adenosine requires no [[hepatic]] or [[renal]] function for its activation or inactivation, [[hepatic]] and [[renal]] failure would not be expected to alter its effectiveness or tolerability.<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970613
Adenosine
2014-05-14T05:35:09Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.<br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=For rapid bolus [[intravenous]] use only.<br />
<br />
Adenosine [[injection]] should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a [[vein]] or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
*'''Adult Patients'''<br />
<br />
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous ([[CVP]] or other) administration of adenosine has not been systematically studied.<br />
<br />
Initial dose is given as a rapid [[intravenous]] bolus (administered over a 1 to 2 second period). If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, 12 mg should be given as a rapid [[intravenous]] bolus. This 12 mg dose may be repeated a second time if required.<br />
<br />
*'''Pediatric Patients'''<br />
<br />
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis. For pediatric patients with a body weight < 50 kg, an initial dose of 0.05 to 0.1 mg/kg as a rapid IV bolus is given either centrally or peripherally. A saline flush should follow. If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used. For [[pediatric]] patients with a body weight ≥ 50 kg, administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for adult and pediatric patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|monitoring======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|IVCompat=There is limited information about the compatibility of Adenosine and IV administrations.<br />
|overdose====Acute Overdose===<br />
The [[half-life]] of adenosine [[injection]] is less than 10 seconds. Thus, [[adverse effect]]s are generally rapidly self-limiting.<br />
====Management====<br />
Treatment of any prolonged [[adverse effect]]s should be individualized and be directed toward the specific effect. [[Methylxanthine]]s, such as [[caffeine]] and [[theophylline]], are [[competitive antagonist]]s of adenosine. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=Adenosine slows conduction time through the [[AV node|A-V node]], can interrupt the reentry pathways through the [[AV node|A-V node]], and can restore normal [[sinus rhythm]] in patients with [[paroxysmal supraventricular tachycardia]] ([[PSVT]]), including [[PSVT]] associated with [[WPW syndrome|Wolff-Parkinson-White Syndrome]].<br />
<br />
Adenosine is [[competitive antagonist|antagonized competitively]] by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]], and potentiated by blockers of [[nucleoside]] transport such as [[dipyridamole]]. Adenosine is not blocked by [[atropine]].<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=Intravenously administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. This process involves a specific transmembrane nucleoside carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical. Intracellular adenosine is rapidly metabolized either via phosphorylation to adenosine monophosphate by adenosine kinase, or via deamination to inosine by adenosine deaminase in the cytosol. Since adenosine kinase has a lower Km and Vmax than adenosine deaminase, deamination plays a significant role only when cytosolic adenosine saturates the phosphorylation pathway. Inosine formed by deamination of adenosine can leave the cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid. [[Adenosine monophosphate]] formed by [[phosphorylation]] of adenosine is incorporated into the high-energy [[phosphate]] pool. While [[extracellular]] adenosine is primarily cleared by cellular uptake with a [[half-life]] of less than 10 seconds in whole blood, excessive amounts may be [[deamination|deaminated]] by an ecto-form of [[adenosine deaminase]]. As adenosine requires no [[hepatic]] or [[renal]] function for its activation or inactivation, [[hepatic]] and [[renal]] failure would not be expected to alter its effectiveness or tolerability.<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970612
Adenosine
2014-05-14T05:28:23Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.<br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=For rapid bolus [[intravenous]] use only.<br />
<br />
Adenosine [[injection]] should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a [[vein]] or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
*'''Adult Patients'''<br />
<br />
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous ([[CVP]] or other) administration of adenosine has not been systematically studied.<br />
<br />
Initial dose is given as a rapid [[intravenous]] bolus (administered over a 1 to 2 second period). If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, 12 mg should be given as a rapid [[intravenous]] bolus. This 12 mg dose may be repeated a second time if required.<br />
<br />
*'''Pediatric Patients'''<br />
<br />
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis. For pediatric patients with a body weight < 50 kg, an initial dose of 0.05 to 0.1 mg/kg as a rapid IV bolus is given either centrally or peripherally. A saline flush should follow. If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used. For [[pediatric]] patients with a body weight ≥ 50 kg, administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for adult and pediatric patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|monitoring======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|IVCompat=There is limited information about the compatibility of Adenosine and IV administrations.<br />
|overdose====Acute Overdose===<br />
The [[half-life]] of adenosine [[injection]] is less than 10 seconds. Thus, [[adverse effect]]s are generally rapidly self-limiting.<br />
====Management====<br />
Treatment of any prolonged [[adverse effect]]s should be individualized and be directed toward the specific effect. [[Methylxanthine]]s, such as [[caffeine]] and [[theophylline]], are [[competitive antagonist]]s of adenosine. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately. <br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970611
Adenosine
2014-05-14T05:24:57Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.<br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=For rapid bolus [[intravenous]] use only.<br />
<br />
Adenosine [[injection]] should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a [[vein]] or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
*'''Adult Patients'''<br />
<br />
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous ([[CVP]] or other) administration of adenosine has not been systematically studied.<br />
<br />
Initial dose is given as a rapid [[intravenous]] bolus (administered over a 1 to 2 second period). If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, 12 mg should be given as a rapid [[intravenous]] bolus. This 12 mg dose may be repeated a second time if required.<br />
<br />
*'''Pediatric Patients'''<br />
<br />
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis. For pediatric patients with a body weight < 50 kg, an initial dose of 0.05 to 0.1 mg/kg as a rapid IV bolus is given either centrally or peripherally. A saline flush should follow. If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used. For [[pediatric]] patients with a body weight ≥ 50 kg, administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for adult and pediatric patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|monitoring======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|IVCompat=There is limited information about the compatibility of Adenosine and IV administrations. <br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970610
Adenosine
2014-05-14T05:22:19Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.<br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=For rapid bolus [[intravenous]] use only.<br />
<br />
Adenosine [[injection]] should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a [[vein]] or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
*'''Adult Patients'''<br />
<br />
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous ([[CVP]] or other) administration of adenosine has not been systematically studied.<br />
<br />
Initial dose is given as a rapid [[intravenous]] bolus (administered over a 1 to 2 second period). If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, 12 mg should be given as a rapid [[intravenous]] bolus. This 12 mg dose may be repeated a second time if required.<br />
<br />
*'''Pediatric Patients'''<br />
<br />
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis. For pediatric patients with a body weight < 50 kg, an initial dose of 0.05 to 0.1 mg/kg as a rapid IV bolus is given either centrally or peripherally. A saline flush should follow. If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used. For [[pediatric]] patients with a body weight ≥ 50 kg, administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for adult and pediatric patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|monitoring======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|IVCompat====Solution===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Y-Site===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Admixture===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Syringe===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===TPN/TNA===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970609
Adenosine
2014-05-14T05:16:54Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.<br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=For rapid bolus [[intravenous]] use only.<br />
<br />
Adenosine [[injection]] should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a [[vein]] or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
*'''Adult Patients'''<br />
<br />
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous ([[CVP]] or other) administration of adenosine has not been systematically studied.<br />
<br />
Initial dose is given as a rapid [[intravenous]] bolus (administered over a 1 to 2 second period). If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, 12 mg should be given as a rapid [[intravenous]] bolus. This 12 mg dose may be repeated a second time if required.<br />
<br />
*'''Pediatric Patients'''<br />
<br />
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis. For pediatric patients with a body weight < 50 kg, an initial dose of 0.05 to 0.1 mg/kg as a rapid IV bolus is given either centrally or peripherally. A saline flush should follow. If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used. For [[pediatric]] patients with a body weight ≥ 50 kg, administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for adult and pediatric patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|monitoring======Condition 1=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 2=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 3=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
|IVCompat====Solution===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Y-Site===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Admixture===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Syringe===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===TPN/TNA===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970608
Adenosine
2014-05-14T05:15:17Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.<br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=For rapid bolus [[intravenous]] use only.<br />
<br />
Adenosine [[injection]] should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a [[vein]] or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:Adult Patients<br />
<br />
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous ([[CVP]] or other) administration of adenosine has not been systematically studied.<br />
<br />
Initial dose is given as a rapid [[intravenous]] bolus (administered over a 1 to 2 second period). If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, 12 mg should be given as a rapid [[intravenous]] bolus. This 12 mg dose may be repeated a second time if required.<br />
<br />
:Pediatric Patients<br />
<br />
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis. For pediatric patients with a body weight < 50 kg, an initial dose of 0.05 to 0.1 mg/kg as a rapid IV bolus is given either centrally or peripherally. A saline flush should follow. If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used. For [[pediatric]] patients with a body weight ≥ 50 kg, administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for adult and pediatric patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|monitoring======Condition 1=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 2=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 3=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
|IVCompat====Solution===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Y-Site===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Admixture===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Syringe===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===TPN/TNA===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970607
Adenosine
2014-05-14T05:09:08Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.<br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=For rapid bolus [[intravenous]] use only.<br />
<br />
Adenosine injection should be given as a rapid bolus by the peripheral intravenous route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a [[vein]] or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:Adult Patients<br />
<br />
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous (CVP or other) administration of adenosine has not been systematically studied.<br />
<br />
The recommended intravenous doses for adults are as follows:<br />
<br />
:*Initial dose: 6 mg given as a rapid intravenous bolus (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the supraventricular tachycardia within 1 to 2 minutes, 12 mg should be given as a rapid intravenous bolus. This 12 mg dose may be repeated a second time if required.<br />
<br />
:Pediatric Patients<br />
<br />
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis.<br />
<br />
:*Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
**Initial dose: Give 0.05 to 0.1 mg/kg as a rapid IV bolus given either centrally or peripherally. A saline flush should follow.<br />
<br />
**Repeat administration: If conversion of PSVT does not occur within 1 to 2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used.<br />
<br />
:*Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for adult and pediatric patients.<br />
<br />
'''NOTE''': Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|monitoring======Condition 1=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 2=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 3=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
|IVCompat====Solution===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Y-Site===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Admixture===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Syringe===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===TPN/TNA===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970606
Adenosine
2014-05-14T03:18:15Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.<br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=(Oral/Intravenous/etc)<br />
|monitoring======Condition 1=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 2=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 3=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
|IVCompat====Solution===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Y-Site===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Admixture===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Syringe===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===TPN/TNA===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970605
Adenosine
2014-05-14T03:16:26Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|FDAPregCat=C<br />
|useInPregnancyFDA=Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during [[pregnancy]] only if clearly needed.<br />
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant. <br />
|useInLaborDelivery=There is no FDA guidance on use of Adenosine during labor and delivery.<br />
|useInNursing=There is no FDA guidance on use of Adenosine during nursing.<br />
|useInPed=No controlled studies have been conducted in [[pediatric]] patients to establish the safety and [[efficacy]] of adenosine for the conversion of [[paroxysmal supraventricular tachycardia]] ([[PSVT]]). However, [[intravenous]] adenosine has been used for the treatment of [[PSVT]] in [[neonate]]s, [[infant]]s, children and [[adolescent]]s.<br />
|useInGeri=Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in [[geriatric]] patients should be used with caution since this population may have a diminished cardiac function, [[nodal dysfunction]], concomitant diseases or drug therapy that may alter [[hemodynamic]] function and produce severe [[bradycardia]] or [[AV block]].<br />
|useInGender=There is no FDA guidance on use of Adenosine with respect to specific gender.<br />
|useInRace=There is no FDA guidance on use of Adenosine with respect to specific racial populations.<br />
|useInRenalImpair=There is no FDA guidance on use of Adenosine in patients with renal impairment.<br />
|useInHepaticImpair=There is no FDA guidance on use of Adenosine in patients with hepatic impairment.<br />
|useInReproPotential=There is no FDA guidance on use of Adenosine in females of reproductive potential and males.<br />
|useInImmunocomp=There is no FDA guidance on use of Adenosine in patients who are immunocompromised.<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=(Oral/Intravenous/etc)<br />
|monitoring======Condition 1=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 2=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 3=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
|IVCompat====Solution===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Y-Site===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Admixture===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Syringe===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===TPN/TNA===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970603
Adenosine
2014-05-14T02:47:18Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[CCB|calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[AV node|A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|useInPregnancyFDA=(Description)<br />
|useInPregnancyAUS=(Description)<br />
|useInLaborDelivery=(Description)<br />
|useInNursing=(Description)<br />
|useInPed=(Description)<br />
|useInGeri=(Description)<br />
|useInGender=(Description)<br />
|useInRace=(Description)<br />
|useInRenalImpair=(Description)<br />
|useInHepaticImpair=(Description)<br />
|useInReproPotential=(Description)<br />
|useInImmunocomp=(Description)<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=(Oral/Intravenous/etc)<br />
|monitoring======Condition 1=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 2=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 3=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
|IVCompat====Solution===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Y-Site===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Admixture===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Syringe===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===TPN/TNA===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970602
Adenosine
2014-05-14T02:45:49Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=*[[Intravenous]] adenosine has been effectively administered in the presence of other cardioactive drugs, such as [[quinidine]], [[beta-adrenergic blocking agents]], [[calcium channel blocking agents]], and [[angiotensin converting enzyme inhibitor]]s, without any change in the adverse reaction profile.<br />
*[[Digoxin]] and [[verapamil]] use may be rarely associated with [[ventricular fibrillation]] when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the [[SA node|SA]] and [[AV node]]s, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving [[digitalis]] may be rarely associated with [[ventricular fibrillation]].<br />
*The effects of adenosine are antagonized by [[methylxanthine]]s such as [[caffeine]] and [[theophylline]]. In the presence of these [[methylxanthine]]s, larger doses of adenosine may be required or adenosine may not be effective. <br />
*Adenosine effects are potentiated by [[dipyridamole]]. Thus, smaller doses of adenosine may be effective in the presence of [[dipyridamole]]. <br />
*[[Carbamazepine]] has been reported to increase the degree of [[heart block]] produced by other agents. As the primary effect of adenosine is to decrease conduction through the [[A-V node]], higher degrees of [[heart block]] may be produced in the presence of [[carbamazepine]].<br />
|useInPregnancyFDA=(Description)<br />
|useInPregnancyAUS=(Description)<br />
|useInLaborDelivery=(Description)<br />
|useInNursing=(Description)<br />
|useInPed=(Description)<br />
|useInGeri=(Description)<br />
|useInGender=(Description)<br />
|useInRace=(Description)<br />
|useInRenalImpair=(Description)<br />
|useInHepaticImpair=(Description)<br />
|useInReproPotential=(Description)<br />
|useInImmunocomp=(Description)<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=(Oral/Intravenous/etc)<br />
|monitoring======Condition 1=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 2=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 3=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
|IVCompat====Solution===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Y-Site===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Admixture===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Syringe===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===TPN/TNA===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970601
Adenosine
2014-05-14T02:35:48Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with [[intravenous]] adenosine used in controlled U.S. clinical trials. The [[placebo]] group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
|drugInteractions=* Drug 1<br />
* Drug 2<br />
* Drug 3<br />
* Drug 4<br />
* Drug 5<br />
<br />
=====Drug 1=====<br />
<br />
(Description)<br />
<br />
=====Drug 2=====<br />
<br />
(Description)<br />
<br />
=====Drug 3=====<br />
<br />
(Description)<br />
<br />
=====Drug 4=====<br />
<br />
(Description)<br />
<br />
=====Drug 5=====<br />
<br />
(Description)<br />
|useInPregnancyFDA=(Description)<br />
|useInPregnancyAUS=(Description)<br />
|useInLaborDelivery=(Description)<br />
|useInNursing=(Description)<br />
|useInPed=(Description)<br />
|useInGeri=(Description)<br />
|useInGender=(Description)<br />
|useInRace=(Description)<br />
|useInRenalImpair=(Description)<br />
|useInHepaticImpair=(Description)<br />
|useInReproPotential=(Description)<br />
|useInImmunocomp=(Description)<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=(Oral/Intravenous/etc)<br />
|monitoring======Condition 1=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 2=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 3=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
|IVCompat====Solution===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Y-Site===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Admixture===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Syringe===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===TPN/TNA===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970600
Adenosine
2014-05-14T02:34:03Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=The following reactions were reported with intravenous adenosine used in controlled U.S. clinical trials. The placebo group had a less than 1% rate of all of these reactions.<br />
<br />
======Cardiovascular======<br />
<br />
:Facial flushing (18%), [[headache]] (2%), sweating, [[palpitation]]s, [[chest pain]], [[hypotension]] (less than 1%).<br />
<br />
======Respiratory======<br />
<br />
:Shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), [[hyperventilation]], head pressure (less than 1%).<br />
<br />
======Central Nervous System======<br />
<br />
:Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).<br />
<br />
======Gastrointestinal======<br />
<br />
:[[Nausea]] (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).<br />
<br />
|postmarketing=The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.<br />
<br />
======Cardiovascular======<br />
<br />
:Prolonged [[asystole]], [[ventricular tachycardia]], [[ventricular fibrillation]], transient increase in blood pressure, [[bradycardia]], [[atrial fibrillation]], and [[Torsade de Pointes]].<br />
<br />
======Respiratory======<br />
<br />
:Bronchospasm<br />
<br />
======Central Nervous System======<br />
<br />
:[[Seizure]] activity, including [[tonic clonic seizure|tonic clonic (grand mal) seizures]], and loss of consciousness.<br />
<br />
|drugInteractions=* Drug 1<br />
* Drug 2<br />
* Drug 3<br />
* Drug 4<br />
* Drug 5<br />
<br />
=====Drug 1=====<br />
<br />
(Description)<br />
<br />
=====Drug 2=====<br />
<br />
(Description)<br />
<br />
=====Drug 3=====<br />
<br />
(Description)<br />
<br />
=====Drug 4=====<br />
<br />
(Description)<br />
<br />
=====Drug 5=====<br />
<br />
(Description)<br />
|useInPregnancyFDA=(Description)<br />
|useInPregnancyAUS=(Description)<br />
|useInLaborDelivery=(Description)<br />
|useInNursing=(Description)<br />
|useInPed=(Description)<br />
|useInGeri=(Description)<br />
|useInGender=(Description)<br />
|useInRace=(Description)<br />
|useInRenalImpair=(Description)<br />
|useInHepaticImpair=(Description)<br />
|useInReproPotential=(Description)<br />
|useInImmunocomp=(Description)<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=(Oral/Intravenous/etc)<br />
|monitoring======Condition 1=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 2=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 3=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
|IVCompat====Solution===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Y-Site===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Admixture===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Syringe===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===TPN/TNA===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970451
Adenosine
2014-05-13T04:44:55Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[AV node|A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitation|resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitation|resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [[premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[AV block|A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body]] [[chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
|clinicalTrials=======Central Nervous System======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Cardiovascular======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Respiratory======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Gastrointestinal======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Hypersensitive Reactions======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Miscellaneous======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
=====Condition 2=====<br />
<br />
======Central Nervous System======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Cardiovascular======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Respiratory======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Gastrointestinal======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Hypersensitive Reactions======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Miscellaneous======<br />
<br />
: (list/description of adverse reactions)<br />
|postmarketing=(Description)<br />
|drugInteractions=* Drug 1<br />
* Drug 2<br />
* Drug 3<br />
* Drug 4<br />
* Drug 5<br />
<br />
=====Drug 1=====<br />
<br />
(Description)<br />
<br />
=====Drug 2=====<br />
<br />
(Description)<br />
<br />
=====Drug 3=====<br />
<br />
(Description)<br />
<br />
=====Drug 4=====<br />
<br />
(Description)<br />
<br />
=====Drug 5=====<br />
<br />
(Description)<br />
|useInPregnancyFDA=(Description)<br />
|useInPregnancyAUS=(Description)<br />
|useInLaborDelivery=(Description)<br />
|useInNursing=(Description)<br />
|useInPed=(Description)<br />
|useInGeri=(Description)<br />
|useInGender=(Description)<br />
|useInRace=(Description)<br />
|useInRenalImpair=(Description)<br />
|useInHepaticImpair=(Description)<br />
|useInReproPotential=(Description)<br />
|useInImmunocomp=(Description)<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=(Oral/Intravenous/etc)<br />
|monitoring======Condition 1=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 2=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 3=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
|IVCompat====Solution===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Y-Site===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Admixture===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Syringe===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===TPN/TNA===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970450
Adenosine
2014-05-13T04:40:54Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======[[Heart Block]]=====<br />
<br />
*Adenosine [[injection]] exerts its effect by decreasing conduction through the [[A-V node]] and may produce a short lasting [[first degree AV block|first]]-, [[second degree AV block|second]]- or [[third degree AV block|third-degree heart block]]. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short [[half-life]] of adenosine, these effects are generally self-limiting. Appropriate [[resuscitative]] measures should be available.<br />
*Transient or prolonged episodes of [[asystole]] have been reported with fatal outcomes in some cases. Rarely, [[ventricular fibrillation]] has been reported following adenosine administration, including both [[resuscitated]] and fatal events. In most instances, these cases were associated with the concomitant use of [[digoxin]] and, less frequently with [[digoxin]] and [[verapamil]]. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving [[digoxin]] or [[digoxin]] and [[verapamil]] in combination.<br />
<br />
=====[[Arrhythmia]]s at Time of Conversion=====<br />
<br />
*At the time of conversion to normal [[sinus rhythm]], a variety of new rhythms may appear on the [[electrocardiogram]]. They generally last only a few seconds without intervention, and may take the form of [premature ventricular contraction]]s, [[atrial premature contraction]]s, [[atrial fibrillation]], [[sinus bradycardia]], [[sinus tachycardia]], skipped beats, and varying degrees of [[A-V nodal block]]. Such findings were seen in 55% of patients.<br />
<br />
=====[[Bronchoconstriction]]=====<br />
<br />
*Adenosine is a [[respiratory stimulant]] (probably through activation of [[carotid body chemoreceptor]]s) and [[intravenous]] administration in man has been shown to increase [[minute ventilation]] (Ve) and reduce arterial PCO2 causing [[respiratory alkalosis]].<br />
*Adenosine administered by [[inhalation]] has been reported to cause [[bronchoconstriction]] in [[asthma]]tic patients, presumably due to [[mast cell]] [[degranulation]] and [[histamine]] release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with [[asthma]] and mild to moderate exacerbation of their symptoms has been reported. [[Respiratory]] compromise has occurred during adenosine infusion in patients with [[obstructive pulmonary disease]]. Adenosine should be used with caution in patients with [[obstructive lung disease]] not associated with [[bronchoconstriction]] (e.g., [[emphysema]], [[bronchitis]], etc.) and should be avoided in patients with [[bronchoconstriction]] or [[bronchospasm]] (e.g., [[asthma]]). Adenosine should be discontinued in any patient who develops severe [[respiratory]] difficulties.<br />
<br />
|clinicalTrials=======Central Nervous System======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Cardiovascular======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Respiratory======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Gastrointestinal======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Hypersensitive Reactions======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Miscellaneous======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
=====Condition 2=====<br />
<br />
======Central Nervous System======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Cardiovascular======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Respiratory======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Gastrointestinal======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Hypersensitive Reactions======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Miscellaneous======<br />
<br />
: (list/description of adverse reactions)<br />
|postmarketing=(Description)<br />
|drugInteractions=* Drug 1<br />
* Drug 2<br />
* Drug 3<br />
* Drug 4<br />
* Drug 5<br />
<br />
=====Drug 1=====<br />
<br />
(Description)<br />
<br />
=====Drug 2=====<br />
<br />
(Description)<br />
<br />
=====Drug 3=====<br />
<br />
(Description)<br />
<br />
=====Drug 4=====<br />
<br />
(Description)<br />
<br />
=====Drug 5=====<br />
<br />
(Description)<br />
|useInPregnancyFDA=(Description)<br />
|useInPregnancyAUS=(Description)<br />
|useInLaborDelivery=(Description)<br />
|useInNursing=(Description)<br />
|useInPed=(Description)<br />
|useInGeri=(Description)<br />
|useInGender=(Description)<br />
|useInRace=(Description)<br />
|useInRenalImpair=(Description)<br />
|useInHepaticImpair=(Description)<br />
|useInReproPotential=(Description)<br />
|useInImmunocomp=(Description)<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=(Oral/Intravenous/etc)<br />
|monitoring======Condition 1=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 2=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 3=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
|IVCompat====Solution===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Y-Site===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Admixture===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Syringe===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===TPN/TNA===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970449
Adenosine
2014-05-13T04:29:35Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or symptomatic [[bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======Conidition 1=====<br />
<br />
(Description)<br />
|clinicalTrials=======Central Nervous System======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Cardiovascular======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Respiratory======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Gastrointestinal======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Hypersensitive Reactions======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Miscellaneous======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
=====Condition 2=====<br />
<br />
======Central Nervous System======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Cardiovascular======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Respiratory======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Gastrointestinal======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Hypersensitive Reactions======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Miscellaneous======<br />
<br />
: (list/description of adverse reactions)<br />
|postmarketing=(Description)<br />
|drugInteractions=* Drug 1<br />
* Drug 2<br />
* Drug 3<br />
* Drug 4<br />
* Drug 5<br />
<br />
=====Drug 1=====<br />
<br />
(Description)<br />
<br />
=====Drug 2=====<br />
<br />
(Description)<br />
<br />
=====Drug 3=====<br />
<br />
(Description)<br />
<br />
=====Drug 4=====<br />
<br />
(Description)<br />
<br />
=====Drug 5=====<br />
<br />
(Description)<br />
|useInPregnancyFDA=(Description)<br />
|useInPregnancyAUS=(Description)<br />
|useInLaborDelivery=(Description)<br />
|useInNursing=(Description)<br />
|useInPed=(Description)<br />
|useInGeri=(Description)<br />
|useInGender=(Description)<br />
|useInRace=(Description)<br />
|useInRenalImpair=(Description)<br />
|useInHepaticImpair=(Description)<br />
|useInReproPotential=(Description)<br />
|useInImmunocomp=(Description)<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=(Oral/Intravenous/etc)<br />
|monitoring======Condition 1=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 2=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 3=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
|IVCompat====Solution===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Y-Site===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Admixture===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Syringe===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===TPN/TNA===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970448
Adenosine
2014-05-13T04:28:59Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid [[IV]] bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for [[pediatric]] patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or [[symptomatic bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======Conidition 1=====<br />
<br />
(Description)<br />
|clinicalTrials=======Central Nervous System======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Cardiovascular======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Respiratory======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Gastrointestinal======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Hypersensitive Reactions======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Miscellaneous======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
=====Condition 2=====<br />
<br />
======Central Nervous System======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Cardiovascular======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Respiratory======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Gastrointestinal======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Hypersensitive Reactions======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Miscellaneous======<br />
<br />
: (list/description of adverse reactions)<br />
|postmarketing=(Description)<br />
|drugInteractions=* Drug 1<br />
* Drug 2<br />
* Drug 3<br />
* Drug 4<br />
* Drug 5<br />
<br />
=====Drug 1=====<br />
<br />
(Description)<br />
<br />
=====Drug 2=====<br />
<br />
(Description)<br />
<br />
=====Drug 3=====<br />
<br />
(Description)<br />
<br />
=====Drug 4=====<br />
<br />
(Description)<br />
<br />
=====Drug 5=====<br />
<br />
(Description)<br />
|useInPregnancyFDA=(Description)<br />
|useInPregnancyAUS=(Description)<br />
|useInLaborDelivery=(Description)<br />
|useInNursing=(Description)<br />
|useInPed=(Description)<br />
|useInGeri=(Description)<br />
|useInGender=(Description)<br />
|useInRace=(Description)<br />
|useInRenalImpair=(Description)<br />
|useInHepaticImpair=(Description)<br />
|useInReproPotential=(Description)<br />
|useInImmunocomp=(Description)<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=(Oral/Intravenous/etc)<br />
|monitoring======Condition 1=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 2=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 3=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
|IVCompat====Solution===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Y-Site===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Admixture===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Syringe===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===TPN/TNA===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970447
Adenosine
2014-05-13T04:27:32Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid IV bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for pediatric patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=*[[Second degree AV block|Second]]- or [[Third degree AV block|third-degree A-V block]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*[[Sinus node disease]], such as [[sick sinus syndrome]] or [[symptomatic bradycardia]] (except in patients with a functioning [[artificial pacemaker]]).<br />
*Known [[hypersensitivity]] to adenosine.<br />
|warnings======Conidition 1=====<br />
<br />
(Description)<br />
|clinicalTrials=======Central Nervous System======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Cardiovascular======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Respiratory======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Gastrointestinal======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Hypersensitive Reactions======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Miscellaneous======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
=====Condition 2=====<br />
<br />
======Central Nervous System======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Cardiovascular======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Respiratory======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Gastrointestinal======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Hypersensitive Reactions======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Miscellaneous======<br />
<br />
: (list/description of adverse reactions)<br />
|postmarketing=(Description)<br />
|drugInteractions=* Drug 1<br />
* Drug 2<br />
* Drug 3<br />
* Drug 4<br />
* Drug 5<br />
<br />
=====Drug 1=====<br />
<br />
(Description)<br />
<br />
=====Drug 2=====<br />
<br />
(Description)<br />
<br />
=====Drug 3=====<br />
<br />
(Description)<br />
<br />
=====Drug 4=====<br />
<br />
(Description)<br />
<br />
=====Drug 5=====<br />
<br />
(Description)<br />
|useInPregnancyFDA=(Description)<br />
|useInPregnancyAUS=(Description)<br />
|useInLaborDelivery=(Description)<br />
|useInNursing=(Description)<br />
|useInPed=(Description)<br />
|useInGeri=(Description)<br />
|useInGender=(Description)<br />
|useInRace=(Description)<br />
|useInRenalImpair=(Description)<br />
|useInHepaticImpair=(Description)<br />
|useInReproPotential=(Description)<br />
|useInImmunocomp=(Description)<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=(Oral/Intravenous/etc)<br />
|monitoring======Condition 1=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 2=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 3=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
|IVCompat====Solution===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Y-Site===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Admixture===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Syringe===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===TPN/TNA===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar
https://www.wikidoc.org/index.php?title=Adenosine&diff=970446
Adenosine
2014-05-13T04:23:42Z
<p>Shankar Kumar: </p>
<hr />
<div>{{DrugProjectFormSinglePage<br />
|authorTag={{Shankar}}<br />
|genericName=Adenosine<br />
|aOrAn=an<br />
|drugClass=Antiarrhythmic<br />
|indication=[[paroxysmal supraventricular tachycardia]] ([[PSVT]])<br />
|adverseReactions=facial flushing (18%), shortness of breath/ [[dyspnea]] (12%), chest pressure (7%), and [[nausea]] (3%)<br />
|blackBoxWarningTitle=Warning Title<br />
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)<br />
|fdaLIADAdult======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
For rapid bolus [[intravenous]] use only. Adenosine injection should be given as a rapid bolus by the peripheral [[intravenous]] route. To be certain the solution reaches the [[systemic circulation]], it should be administered either directly into a vein or, if given into an [[IV]] line, it should be given as close to the patient as possible and followed by a rapid saline flush.<br />
<br />
:*Initial dose: '''Adenosine 6 mg given as a rapid [[intravenous]] bolus''' (administered over a 1 to 2 second period).<br />
<br />
:*Repeat administration: If the first dose does not result in elimination of the [[supraventricular tachycardia]] within 1 to 2 minutes, '''Adenosine 12 mg''' should be given as a '''rapid [[intravenous]] bolus'''. This 12 mg dose may be repeated a second time if required.<br />
<br />
Doses greater than 12 mg are not recommended for adult patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelAdultGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelAdultNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|fdaLIADPed======Paroxysmal Supraventricular Tachycardia=====<br />
<br />
* Dosing Information<br />
<br />
The dosages used in [[neonate]]s, [[infant]]s, children and [[adolescent]]s were equivalent to those administered to adults on a weight basis.<br />
<br />
Pediatric Patients with a Body Weight < 50 kg:<br />
<br />
:*Initial dose: Give '''Adenosine 0.05 to 0.1 mg/kg as a rapid IV bolus''' given either centrally or peripherally. A saline flush should follow.<br />
<br />
:*Repeat administration: If conversion of [[PSVT]] does not occur within 1 to 2 minutes, additional bolus [[injection]]s of adenosine can be administered at incrementally higher doses, '''increasing the amount given by 0.05 to 0.1 mg/kg'''. Follow each bolus with a saline flush. This process should continue until [[sinus rhythm]] is established or a '''maximum single dose of 0.3 mg/kg''' is used.<br />
<br />
Pediatric Patients with a Body Weight ≥ 50 kg:<br />
<br />
:*Administer the adult dose.<br />
<br />
Doses greater than 12 mg are not recommended for pediatric patients.<br />
<br />
'''NOTE''': [[Parenteral]] drug products should be inspected visually for particulate matter and discoloration prior to administration.<br />
|offLabelPedGuideSupport======Condition 1=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Developed by: (Organisation)<br />
<br />
* Class of Recommendation: (Class) (Link)<br />
<br />
* Strength of Evidence: (Category A/B/C) (Link)<br />
<br />
* Dosing Information/Recommendation<br />
<br />
:* (Dosage)<br />
|offLabelPedNoGuideSupport======Condition 1=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 2=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
<br />
=====Condition 3=====<br />
<br />
* Dosing Information<br />
<br />
:* (Dosage)<br />
|contraindications=* Condition 1<br />
* Condition 2<br />
* Condition 3<br />
* Condition 4<br />
* Condition 5<br />
|warnings======Conidition 1=====<br />
<br />
(Description)<br />
|clinicalTrials=======Central Nervous System======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Cardiovascular======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Respiratory======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Gastrointestinal======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Hypersensitive Reactions======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Miscellaneous======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
=====Condition 2=====<br />
<br />
======Central Nervous System======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Cardiovascular======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Respiratory======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Gastrointestinal======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Hypersensitive Reactions======<br />
<br />
: (list/description of adverse reactions)<br />
<br />
======Miscellaneous======<br />
<br />
: (list/description of adverse reactions)<br />
|postmarketing=(Description)<br />
|drugInteractions=* Drug 1<br />
* Drug 2<br />
* Drug 3<br />
* Drug 4<br />
* Drug 5<br />
<br />
=====Drug 1=====<br />
<br />
(Description)<br />
<br />
=====Drug 2=====<br />
<br />
(Description)<br />
<br />
=====Drug 3=====<br />
<br />
(Description)<br />
<br />
=====Drug 4=====<br />
<br />
(Description)<br />
<br />
=====Drug 5=====<br />
<br />
(Description)<br />
|useInPregnancyFDA=(Description)<br />
|useInPregnancyAUS=(Description)<br />
|useInLaborDelivery=(Description)<br />
|useInNursing=(Description)<br />
|useInPed=(Description)<br />
|useInGeri=(Description)<br />
|useInGender=(Description)<br />
|useInRace=(Description)<br />
|useInRenalImpair=(Description)<br />
|useInHepaticImpair=(Description)<br />
|useInReproPotential=(Description)<br />
|useInImmunocomp=(Description)<br />
|othersTitle=Others<br />
|useInOthers=(Description)<br />
|administration=(Oral/Intravenous/etc)<br />
|monitoring======Condition 1=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 2=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
<br />
=====Condition 3=====<br />
<br />
(Description regarding monitoring, from ''Warnings'' section)<br />
|IVCompat====Solution===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Y-Site===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Admixture===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===Syringe===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
===TPN/TNA===<br />
<br />
====Compatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Not Tested====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Variable====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
<br />
====Incompatible====<br />
<br />
* Solution 1<br />
* Solution 2<br />
* Solution 3<br />
|overdose====Acute Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
<br />
===Chronic Overdose===<br />
<br />
====Signs and Symptoms====<br />
<br />
(Description)<br />
<br />
====Management====<br />
<br />
(Description)<br />
|drugBox={{Drugbox2<br />
| verifiedrevid = <br />
| IUPAC_name = <br />
| image = <br />
| drug_name = <br />
<br />
<!--Clinical data--><br />
| tradename = <br />
| MedlinePlus = <br />
| licence_US = <br />
| pregnancy_AU = <br />
| pregnancy_US = <br />
| legal_status = <br />
| routes_of_administration =<br />
<br />
<!--Pharmacokinetic data--><br />
| bioavailability = <br />
| metabolism = <br />
| elimination_half-life = <br />
| excretion = <br />
<br />
<!--Identifiers--><br />
| CAS_number_Ref = <br />
| CAS_number = <br />
| ATC_prefix = <br />
| ATC_suffix = <br />
| PubChem = <br />
| IUPHAR_ligand = <br />
| DrugBank_Ref = <br />
| DrugBank = <br />
| ChemSpiderID_Ref = <br />
| ChemSpiderID = <br />
| UNII_Ref = <br />
| UNII = <br />
| KEGG_Ref = <br />
| KEGG = <br />
| ChEBI_Ref = <br />
| ChEBI = <br />
| ChEMBL_Ref = <br />
| ChEMBL = <br />
<br />
<!--Chemical data--><br />
| C= | H= | N= | O= <br />
| molecular_weight = <br />
| smiles = <br />
| InChI = <br />
| InChIKey = <br />
| StdInChI_Ref = <br />
| StdInChI = <br />
| StdInChIKey_Ref = <br />
| StdInChIKey = <br />
| melting_point = <br />
}}<br />
|mechAction=(Description)<br />
|structure=(Description with picture)<br />
|PD=(Description)<br />
|PK=(Description)<br />
|nonClinToxic=(Description)<br />
|clinicalStudies======Condition 1=====<br />
<br />
(Description)<br />
<br />
=====Condition 2=====<br />
<br />
(Description)<br />
<br />
=====Condition 3=====<br />
<br />
(Description)<br />
|howSupplied=(Description)<br />
|fdaPatientInfo=(Patient Counseling Information)<br />
|nlmPatientInfo=(Link to patient information page)<br />
|alcohol=Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.<br />
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)<br />
* (Paired Confused Name 2a) — (Paired Confused Name 2b)<br />
* (Paired Confused Name 3a) — (Paired Confused Name 3b)<br />
}}<br />
<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}<br />
|fileName=}}</div>
Shankar Kumar