|
|
| (3 intermediate revisions by 2 users not shown) |
| Line 1: |
Line 1: |
| {{DrugProjectFormSinglePage
| | #REDIRECT [[L-Asparaginase]] |
| |authorTag={{AV}}
| |
| |genericName=Asparaginase
| |
| |aOrAn=an
| |
| |drugClass=[[antineoplastic agent]]
| |
| |indicationType=treatment
| |
| |indication=as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with [[acute lymphoblastic leukemia]] (ALL) who have developed hypersensitivity to [[E. coli]]-derived asparaginase.
| |
| |adverseReactions=[[hypersensitivity reactions]], [[Pancreatitis]], [[Glucose intolerance]], [[Thrombosis]] and [[hemorrhage]] systemic hypersensitivity, [[hyperglycemia]], transaminases abnormal, [[fever]], [[pancreatitis]], local reactions, [[vomiting]], [[nausea]], [[thrombosis]], [[hyperbilirubinemia]], [[abdominal pain]]/discomfort, and [[diarrhea]].<!--Black Box Warning-->
| |
| |blackBoxWarningTitle=Title
| |
| |blackBoxWarningBody=<i><span style="color:#FF0000;">ConditionName: </span></i>
| |
| | |
| * Content
| |
| | |
| <!--Adult Indications and Dosage-->
| |
| | |
| <!--FDA-Labeled Indications and Dosage (Adult)-->
| |
| |fdaLIADAdult======Acute lymphoblastic leukemia (ALL)=====
| |
| *Asparaginase is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with [[acute lymphoblastic leukemia]] (ALL) who have developed [[hypersensitivity]] to [[E. coli]]-derived asparaginase.
| |
| =====Recommended Dose=====
| |
| *To substitute for a dose of pegaspargase:
| |
| :*The recommended dose for each planned dose of [[pegaspargase]] is 25,000 International Units/m2 administered intramuscularly or intravenously three times a week (Monday/Wednesday/Friday) for six doses.
| |
| *To substitute for a dose of native E. coli asparaginase:
| |
| :*The recommended dose is 25,000 International Units/m2 administered intramuscularly or intravenously for each scheduled dose of native [[E. coli]] asparaginase within a treatment.
| |
| :*When administering asparaginase intravenously, consider monitoring nadir (pre-dose) serum asparaginase activity (NSAA) levels and switching to intramuscular administration if desired NSAA levels are not achieved [see Clinical Pharmacology (12.3)].
| |
| ===== Preparation and Handling Instructions=====
| |
| *Visually inspect the asparaginase powder for foreign particulate matter and discoloration prior to reconstitution. Discard vial if present.
| |
| *Reconstitute the contents of each vial by slowly injecting 1 or 2 mL of preservative free sterile sodium chloride (0.9%) injection (USP) against the inner vial wall.
| |
| *Do not forcefully inject solution for reconstitution directly onto or into the powder. When reconstituted with 1 mL the resultant concentration is 10,000 International Units per mL. When reconstituted with 2 mL the resultant concentration is 5,000 International Units per mL.
| |
| *Dissolve contents by gentle mixing or swirling. Do not shake or invert vial.
| |
| *When reconstituted, asparaginase should be a clear, colorless solution. Inspect the solution after reconstitution and discard if any visible particles or protein aggregates are present.
| |
| *Calculate the dose needed and the volume needed to obtain the calculated dose.
| |
| *Withdraw the volume containing the calculated dose from the vial into a polypropylene syringe within 15 minutes of reconstitution. For intravenous use, slowly inject the reconstituted asparaginase into an IV infusion bag containing 100 mL of normal saline acclimatized to room temperature. Do not shake or squeeze the IV bag.
| |
| *If partial vial is used, do not save or reuse the unused drug for later administration. Discard unused portions.
| |
| * Do not freeze or refrigerate reconstituted solution and administer within 4 hours or discard [see How Supplied/Storage and Handling (16)].
| |
| | |
| =====Administration Instructions=====
| |
| *Asparaginase solution can be administered by intramuscular injection or by intravenous infusion.
| |
| *For intramuscular use, limit the volume of reconstituted asparaginase at a single injection site to 2 mL; if reconstituted dose to be administered is greater than 2 mL, use multiple injection sites.
| |
| *For intravenous use, infuse asparaginase in 100 mL of normal saline over 1 hour. Do not infuse other intravenous drugs through the same intravenous line while infusing asparaginase.
| |
| |offLabelAdultGuideSupport=
| |
| <!--Non–Guideline-Supported Use (Adult)-->
| |
| |offLabelAdultNoGuideSupport=
| |
| There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Asparaginase in adult patients.
| |
| | |
| <!--Pediatric Indications and Dosage-->
| |
| | |
| <!--FDA-Labeled Indications and Dosage (Pediatric)-->
| |
| |fdaLIADPed======Condition1=====
| |
| | |
| * Dosing Information
| |
| | |
| :* Dosage
| |
| | |
| =====Condition2=====
| |
| | |
| There is limited information regarding <i>FDA-Labeled Use</i> of Asparaginase in pediatric patients.
| |
| | |
| <!--Off-Label Use and Dosage (Pediatric)-->
| |
| | |
| <!--Guideline-Supported Use (Pediatric)-->
| |
| |offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Asparaginase in pediatric patients.
| |
| | |
| <!--Non–Guideline-Supported Use (Pediatric)-->
| |
| |contraindications=* History of serious [[hypersensitivity]] reactions to Asparaginase, including [[anaphylaxis]]
| |
| *History of serious [[pancreatitis]]with prior L-asparaginase therapy
| |
| *History of serious [[thrombosis]] with prior L-asparaginase therapy
| |
| *History of serious hemorrhagic events with prior L-asparaginase therapy
| |
| <!--Warnings-->
| |
| |warnings======Hypersensitivity Reactions=====
| |
| *Grade 3 and 4 hypersensitivity reactions after the use of Asparaginase have occurred in 5% of patients in clinical trials [see Adverse Reactions (6.1)].
| |
| *Administer this product in a setting with resuscitation equipment and other agents necessary to treat [[anaphylaxis]]. If a serious [[hypersensitivity]] reaction occurs, discontinue Asparaginase and initiate appropriate therapy.
| |
| =====Pancreatitis=====
| |
| *[[Pancreatitis]] has been reported in 4% of patients in clinical trials.
| |
| *Evaluate patients with symptoms compatible with pancreatitis to establish a diagnosis. Discontinue Asparaginase for severe or hemorrhagic pancreatitis manifested by abdominal pain > 72 hours and amylase elevation ≥ 2.0 x ULN. Severe pancreatitis is a contraindication to additional asparaginase administration. In the case of mild pancreatitis, hold Asparaginase until the signs and symptoms subside and amylase levels return to normal. After resolution, treatment with Asparaginase may be resumed.
| |
| ===== Glucose Intolerance=====
| |
| *Glucose intolerance has been reported in 5% of patients receiving Asparaginase in clinical trials [see Adverse Reactions (6.1)]. In some cases glucose intolerance may be irreversible. Monitor glucose levels in patients at baseline and periodically during treatment. Administer insulin therapy as necessary in patients with hyperglycemia.
| |
| =====Thrombosis and Hemorrhage=====
| |
| *Serious thrombotic events, including sagittal sinus thrombosis and pulmonary embolism have been reported with both E. coli and Erwinia-derived L-asparaginase therapy. The following coagulation proteins were decreased in the majority of patients after a 2-week course of Asparaginase by intramuscular administration: fibrinogen, protein C activity, protein S activity, and anti-thrombin III. *Discontinue Asparaginase for a thrombotic or hemorrhagic event until symptoms resolve; after resolution, treatment with Asparaginase may be resumed.
| |
| | |
| | |
| | |
| <!--Adverse Reactions-->
| |
| | |
| <!--Clinical Trials Experience-->
| |
| |clinicalTrials=The following serious adverse reactions are discussed in greater detail in other sections of the label:
| |
| | |
| Hypersensitivity reactions [ see Warnings and Precautions (5.1)]
| |
| Pancreatitis [ see Warnings and Precautions (5.2)]
| |
| Glucose intolerance [ see Warnings and Precautions (5.3)]
| |
| Thrombosis and hemorrhage [ see Warnings and Precautions (5.4)]
| |
| The most common adverse reactions (incidence 1% or greater) with Asparaginase treatment are systemic hypersensitivity, hyperglycemia, transaminases abnormal, fever, pancreatitis, local reactions, vomiting, nausea, thrombosis, hyperbilirubinemia, abdominal pain/discomfort, and diarrhea.
| |
| 6.1 Clinical Studies
| |
| Because clinical trials are conducted under controlled, but widely varying conditions, adverse reaction rates observed in clinical trials of Asparaginase cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice.
| |
| | |
| The data presented below are based on information collected from Study 1, a single-arm, multi-center, open-label, safety and clinical pharmacology trial (intramuscular administration), the Asparaginase Master Treatment Protocol (EMTP), an expanded access program (both intramuscular, intravenous, and other or unknown administration), and Study 2, a single-arm, multi-center, open-label, pharmacokinetic (PK) study trial of intravenous administration of Asparaginase.
| |
| | |
| Study 1 enrolled 58 patients treated on National Cancer Institute (NCI)-sponsored cooperative group ALL protocols who were unable to continue to receive pegaspargase due to hypersensitivity reactions. Patients received 6 doses of Asparaginase 25,000 International Units/m2 intramuscularly on a Monday, Wednesday, and Friday schedule as a replacement for each scheduled dose of pegaspargase remaining on their original treatment protocol. The Study 1 population included patients with a median age of 11 years (2 to 18 years); 59% were male, 78% were White, 10% were Black/African American, 5% were Asian, and 7% were other or unknown. A total of 35% were Hispanic or Latino. In Study 1, the number of Asparaginase courses ranged from 1 to 9. In this study, 76% (44 of 58) completed all planned therapy. Fourteen (24%) patients stopped therapy prior to completion; seven due to allergic reactions, five due to physician or patient choice, one due to disease progression, and one due to discontinuation during frontline protocol. All other chemotherapy was continued according to the patient’s prescribed treatment regimen [see Clinical Studies (14)].
| |
| | |
| Study 2 enrolled 30 patients [29 were being treated for ALL and one for lymphoblastic lymphoma (LBL)] following allergy to native E. coli asparaginase or pegaspargase. Patients received Asparaginase 25,000 International Unit/m2/dose, administered by intravenous infusion on a Monday, Wednesday, and Friday schedule (6 doses) as a replacement for doses remaining on their original treatment plan. The Study 2 population included patients with a median age of 7 years (1 to 17 years); 63% were male, 27% were Hispanic or Latino, 83% were White, 3% were Black/African American, 7% were Asian, and 7% were other (American Indian, Alaska Native or Indian) [see Clinical Studies (14)].
| |
| | |
| The EMTP trial enrolled 1368 patients with ALL or lymphoblastic lymphoma who received Asparaginase after developing systemic hypersensitivity to an E. coli-derived asparaginase. Of these 1368 patients, safety data were received for 940 patients with a median age of 9 years (0 to 76 years), 63% were male, 91% with leukemia, 3% with lymphoma, and 6% with unknown disease information. Patients received Asparaginase according to several schedules, and treatment center specifications with doses that ranged from 20,000 to 25,000 International Units/m2. The route of administration was intramuscular n=852, intravenous n=29, other or unknown n=59. In the EMTP trial, the planned number of doses of Asparaginase ranged from 3 to 48 doses. Seventy-eight percent of patients (693 of 893) were able to receive all planned doses to complete their prescribed treatment regimen.
| |
| | |
| In Study 1 and Study 2, safety information was prospectively and systematically collected. In Study 1, all Grades of adverse events were reported for the following adverse events of special interest: allergy, pancreatitis, coagulopathy (hemorrhage, thrombosis or infarct), hyperbilirubinemia, hyperglycemia, hyperlipidemia, ketoacidosis, and CNS events (hemorrhage, thrombosis or infarction, and cerebral venous thrombosis) and only Grade 3 and 4 events were reported for other adverse events. In Study 2 all adverse events of all Grades were prospectively collected. In the EMTP trial, safety data were derived from case report forms that collected adverse event information. The forms specifically requested information on occurrence of allergic reactions, thrombotic events, hemorrhagic events, hepatobiliary disorders, pancreatic disorders, and hyperglycemia.
| |
| | |
| The incidence of non-hematologic, non-infectious, adverse events (all Grades) in Study 1, Study 2, and the EMTP trial is provided in Table 1.
| |
| [[File:Asparaginase01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
| |
| 6.2 Immunogenicity
| |
| As with most therapeutic proteins, patients may develop anti-drug antibodies (ADA) to Asparaginase.
| |
| | |
| In a study with Asparaginase treatment by intramuscular administration (Study 1), 6 of 56 (11%) patients treated with Asparaginase developed antibodies to Asparaginase. Of these 6 ADA positive patients, one experienced a hypersensitivity reaction during Study 1 (2%, 1 of 56). None of these 6 patients had neutralizing antibodies.
| |
| | |
| In a study with Asparaginase treatment by intravenous administration (Study 2), 4 of 30 (13.3%) patients treated with Asparaginase developed anti-Asparaginase antibodies. Of these 4 patients who developed anti-Asparaginase antibodies, 3 experienced hypersensitivity reactions (10%, 3 of 30) during the study. None of these 4 patients had neutralizing antibodies.
| |
| | |
| The presence of ADA to Asparaginase is associated with a higher risk of hypersensitivity reactions in patients who received Asparaginase through intravenous infusion compared to intramuscular administration of Asparaginase.
| |
| | |
| Immunogenicity assay are highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Asparaginase with the incidence of antibodies to other products may be misleading.
| |
| =====Body as a Whole=====
| |
| | |
| | |
| | |
| | |
| =====Cardiovascular=====
| |
| | |
| | |
| | |
| | |
| =====Digestive=====
| |
| | |
| | |
| | |
| | |
| =====Endocrine=====
| |
| | |
| | |
| | |
| | |
| =====Hematologic and Lymphatic=====
| |
| | |
| | |
| | |
| | |
| =====Metabolic and Nutritional=====
| |
| | |
| | |
| | |
| | |
| =====Musculoskeletal=====
| |
| | |
| | |
| | |
| | |
| =====Neurologic=====
| |
| | |
| | |
| | |
| | |
| =====Respiratory=====
| |
| | |
| | |
| | |
| | |
| =====Skin and Hypersensitivy Reactions=====
| |
| | |
| | |
| | |
| | |
| =====Special Senses=====
| |
| | |
| | |
| | |
| | |
| =====Urogenital=====
| |
| | |
| | |
| | |
| | |
| =====Miscellaneous=====
| |
| | |
| | |
| | |
| <!--Postmarketing Experience-->
| |
| |postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of Asparaginase in the drug label.
| |
| | |
| =====Body as a Whole=====
| |
| | |
| | |
| | |
| =====Cardiovascular=====
| |
| | |
| | |
| | |
| =====Digestive=====
| |
| | |
| | |
| | |
| =====Endocrine=====
| |
| | |
| | |
| | |
| =====Hematologic and Lymphatic=====
| |
| | |
| | |
| | |
| =====Metabolic and Nutritional=====
| |
| | |
| | |
| | |
| =====Musculoskeletal=====
| |
| | |
| | |
| | |
| =====Neurologic=====
| |
| | |
| | |
| | |
| =====Respiratory=====
| |
| | |
| | |
| | |
| =====Skin and Hypersensitivy Reactions=====
| |
| | |
| | |
| | |
| =====Special Senses=====
| |
| | |
| | |
| | |
| =====Urogenital=====
| |
| | |
| | |
| | |
| =====Miscellaneous=====
| |
| | |
| | |
| | |
| <!--Drug Interactions-->
| |
| |drugInteractions=* No formal drug interaction studies between Asparaginase and other drugs have been performed.
| |
| | |
| | |
| <!--Use in Specific Populations-->
| |
| |FDAPregCat=C
| |
| |useInPregnancyFDA=*There are no adequate and well-controlled studies of Asparaginase in pregnant women. In embryofetal development studies in rats and rabbits, asparaginase Erwinia chrysanthemi produced embryofetal toxicities and fetal abnormalities. Asparaginase should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
| |
| =====Animal Data=====
| |
| *In embryofetal development studies, asparaginase Erwinia chrysanthemi was administered intramuscularly every other day during the period of organogenesis to pregnant rats (at 500, 1000, or 2000 IU/kg) and rabbits (at 10, 25, and 40 IU/kg). In rats given 2000 IU/kg (approximately 50% of the recommended human dose, adjusted for body surface area), maternal toxicity of decreased body weight gain was observed, as well as a fetal finding of increased incidence of partially undescended thymic tissue.
| |
| *In rabbits, maternal toxicity consisting of decreased body weight was observed at 40 IU/kg (approximately 2% of the recommended human dose, adjusted for body surface area). Increased post-implantation loss, a decrease in the number of live fetuses, and gross abnormalities (e.g., absent kidney, absent accessory lung lobe, additional subclavian artery, and delayed ossification) were observed at doses of ≥10 IU/kg (approximately 0.5% of the recommended human dose, adjusted for body surface area).
| |
| |useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Asparaginase in women who are pregnant.
| |
| |useInLaborDelivery=There is no FDA guidance on use of Asparaginase during labor and delivery.
| |
| |useInNursing=*It is not known whether Asparaginase is secreted in human milk. *Because many drugs are secreted in human milk, and because of the potential for serious adverse reactions in nursing infants from Asparaginase, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
| |
| |useInPed=There is no FDA guidance on the use of Asparaginase with respect to pediatric patients.
| |
| |useInGeri=*The safety and efficacy of Asparaginase has not been studied in geriatric patients.
| |
| |useInGender=There is no FDA guidance on the use of Asparaginase with respect to specific gender populations.
| |
| |useInRace=There is no FDA guidance on the use of Asparaginase with respect to specific racial populations.
| |
| |useInRenalImpair=There is no FDA guidance on the use of Asparaginase in patients with renal impairment.
| |
| |useInHepaticImpair=There is no FDA guidance on the use of Asparaginase in patients with hepatic impairment.
| |
| |useInReproPotential=There is no FDA guidance on the use of Asparaginase in women of reproductive potentials and males.
| |
| |useInImmunocomp=There is no FDA guidance one the use of Asparaginase in patients who are immunocompromised.
| |
| | |
| <!--Administration and Monitoring-->
| |
| |administration=* Oral
| |
| | |
| * Intravenous
| |
| |monitoring=There is limited information regarding <i>Monitoring</i> of Asparaginase in the drug label.
| |
| | |
| * Description
| |
| | |
| <!--IV Compatibility-->
| |
| |IVCompat=There is limited information regarding <i>IV Compatibility</i> of Asparaginase in the drug label.
| |
| | |
| <!--Overdosage-->
| |
| |overdose=*There are no known cases of overdose with Asparaginase.
| |
| | |
| | |
| | |
| <!--Pharmacology-->
| |
| | |
| <!--Drug box 2-->
| |
| |drugBox=[[File:Asparaginase00.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]<!--Mechanism of Action-->
| |
| |mechAction=* Asparaginase Erwinia chrysanthemi catalyzes the deamidation of asparagine to aspartic acid and ammonia, resulting in a reduction in circulating levels of asparagine. The mechanism of action of Asparaginase is thought to be based on the inability of leukemic cells to synthesize asparagine due to lack of asparagine synthetase activity, resulting in cytotoxicity specific for leukemic cells that depend on an exogenous source of amino acid asparagine for their protein metabolism and survival.
| |
| | |
| <!--Structure-->
| |
| |structure=* Asparaginase (asparaginase Erwinia chrysanthemi) contains an asparagine specific enzyme derived from Erwinia chrysanthemi. L-asparaginase is a tetrameric enzyme consisting of four identical subunits, each having a molecular weight of about 35 kDa. The activity of Asparaginase is expressed in terms of International Units.
| |
| *Asparaginase is supplied as a sterile, lyophilized, white powder in vials. Each vial contains 10,000 International Units of asparaginase Erwinia chrysanthemi, and the following inactive ingredients: glucose monohydrate (5.0 mg), sodium chloride (0.5 mg).
| |
| | |
| | |
| | |
| <!--Pharmacodynamics-->
| |
| |PD=There is limited information regarding <i>Pharmacodynamics</i> of Asparaginase in the drug label.
| |
| | |
| <!--Pharmacokinetics-->
| |
| |PK=*Based on a population PK model, the mean (%CV) half-life of intravenous Asparaginase was 7.51 (23.9%) hours in contrast to a mean (%CV) half-life of 15.6 (20%) hours reported for intramuscular Asparaginase. These differences in PK between intravenous and intramuscular Asparaginase are reflected in the proportion of patients with 2-day and 3-day nadir serum asparaginase activity (NSAA) levels of asparaginase Erwinia chrysanthemi ≥ 0.1 or 0.4 IU/mL .
| |
| *Following administration of Asparaginase 25,000 International Units/m2 intramuscularly to 48 ALL patients aged ≥ 2 years to ≤ 18 years in Study 1 on a Monday, Wednesday, and Friday schedule for 6 doses, 100% of patients who completed Course 1 achieved NSAA levels ≥ 0.1 International Units/mL at either 48 hours (n=35) or 72 hours (n=13) post dose 3. Eighty percent (28/35) of those evaluated at 48 hours and 38% (5/13) evaluated at 72 hours had nadir serum asparaginase activity levels ≥ 0.4 International Units/mL [see Clinical Studies (14)].
| |
| *Following intravenous administration of Asparaginase 25,000 International Units/m2 to 24 evaluable patients (aged ≥ 1 year to ≤ 17 years) in Study 2 on a Monday, Wednesday, and Friday schedule, 83% (20/24) and 43% (9/21) of patients who completed Course 1 achieved NSAA levels ≥ 0.1 International Units/mL at 48 hours post-dose 5 and 72 hours post dose 6, respectively. Twenty-nine percent (7/24) of those evaluated at 48 hours and no patients (0/21) evaluated at 72 hours had nadir serum asparaginase activity levels ≥ 0.4 International Units/mL
| |
| | |
| <!--Nonclinical Toxicology-->
| |
| |nonClinToxic======Carcinogenesis, Mutagenesis, Impairment of Fertility=====
| |
| *No long-term carcinogenicity studies in animals have been performed with asparaginase Erwinia chrysanthemi. No studies that assess the mutagenic potential of asparaginase Erwinia chrysanthemi have been conducted.
| |
| *In a fertility and early embryonic development study in rats, asparaginase Erwinia chrysanthemi had no effect on male or female fertility when administered intramuscularly at doses of up to 2000 IU/kg (approximately 50% of the recommended human dose, when adjusted for total body surface area) every other day for a total of 35 doses. Findings in males included decreased sperm count at doses of more than 500 IU/kg (approximately 12% of the recommended human dose).
| |
| | |
| <!--Clinical Studies-->
| |
| |clinicalStudies=The safety and efficacy of Asparaginase was established in Study 1, a single-arm, multi-center, open-label, safety and clinical pharmacology trial. Additional safety data were obtained in the Asparaginase Master Treatment Protocol (EMTP), an expanded access program [see Adverse Reactions (6)]. Study 1 enrolled patients treated on National Cancer Institute (NCI)-sponsored cooperative group ALL protocols who were unable to continue to receive pegaspargase due to hypersensitivity reactions. The main outcome measure was determination of the proportion of patients who achieved a serum trough asparaginase level greater than or equal to 0.1 International Units/mL. Serum trough asparaginase activity ≥ 0.1 International Units/mL has been demonstrated to correlate with asparagine depletion (asparagine < 0.4 mcg/mL or 3 µM) and to serum levels that predict clinical efficacy. Patients received Asparaginase 25,000 International Units/m2 intramuscularly for two weeks (total 6 doses) as a replacement for each scheduled dose of pegaspargase remaining on their original treatment protocol.
| |
| | |
| Fifty-eight patients were enrolled in Study 1, of these 48 were evaluable for the main outcome measure based on availability of pharmacokinetic samples in Course 1. The median age was 11 years (2 to 18 years); 59% were male, 78% were White, 10% were Black/African American, 5% were Asian, and 7% were other or unknown. A total of 35% were Hispanic or Latino.
| |
| | |
| Study 1 met its main outcome measure of demonstrating that greater than 50% of the patients achieved the pre-specified trough asparaginase activity level of ≥ 0.1 International Units/mL at 48 or 72 hours following the third dose. Results for the main outcome measure and for an exploratory analysis using a higher cut-off (trough serum asparaginase activity levels ≥ 0.4 International Units/mL are presented in Table 3 [see Clinical Pharmacology (12.3)].
| |
| | |
| The safety and efficacy of intravenous administration were determined in Study 2 by characterizing the PK of a 25,000 International Units/m2 Asparaginase dose given 3 days per week on a Monday, Wednesday, and Friday schedule for up to 30 weeks. This open-label, single-arm, multicenter PK study enrolled 30 patients. The main outcome measure was determination of the proportion of patients with 2-day NSAA levels (48-hour levels taken after the fifth dose) ≥ 0.1 International Unit/mL in the first 2 weeks of Asparaginase treatment.
| |
| | |
| Of the thirty patients enrolled, 24 were evaluable for the main outcome measure based on the pharmacokinetic samples in Course 1. The median age was 7 years (1-17 years), 63% were male, 27% were Hispanic or Latino, 83% were White, 3% were Black/African American, 7% were Asian, and 7% were other (American Indian, Alaska Native, or Indian).
| |
| | |
| In Study 2, serum asparaginase activity of asparaginase Erwinia chrysanthemi was determined in 24 evaluable patients (aged ≥ 1 year to ≤17 years) following intravenous administration of Asparaginase 25,000 International Units/m2. Five minutes after the 60-minute infusion in Course 1, the mean asparaginase activity level was 12.65 ± 3.16 International Unit/mL post-dose 1 and 12.11 ± 3.11 International Unit/mL post dose 4. The main study objective was met with an asparaginase activity level of ≥ 0.1 International Units/mL 48 hours after the fifth dose observed in 83% of patients. The 72-hour post dose 6 asparaginase activity level of ≥ 0.1 International Unit/mL was the secondary endpoint, with 43% of patients achieving this endpoint. Results are presented in Table 3 [see Clinical Pharmacology (12.3)].
| |
| [[File:Asparaginase02.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
| |
| <!--How Supplied-->
| |
| |howSupplied=* Asparaginase is a sterile, white lyophilized powder supplied in a clear 3 mL glass vial. Each carton of Asparaginase (NDC 57902-249-05) contains 5 vials. Each single vial (NDC 57902-249-01) contains 10,000 International Units asparaginase Erwinia chrysanthemi.
| |
| | |
| <!--Patient Counseling Information-->
| |
| |storage=*Store unused or unopened vials and cartons at 36°F to 46°F (2°C to 8°C). Protect from light. Do not use Asparaginase after the expiration date on the vial.
| |
| |fdaPatientInfo=*Instruct patients on the risk of allergic reactions, including anaphylaxis. Describe the symptoms of allergic reactions, including anaphylaxis, and instruct the patient to seek medical advice immediately if they experience such symptoms.
| |
| *Instruct patients on the risk of pancreatitis and to seek medical advice immediately if they experience abdominal pain.
| |
| *Instruct patients on the risk of hyperglycemia and glucose intolerance. Advise patients to seek medical advice if they experience excessive thirst or any increase in the volume or frequency of urination.
| |
| *Instruct patients on the risk of thrombosis and hemorrhage and to seek medical advice immediately if they experience headache, arm or leg swelling, shortness of breath, and chest pain.
| |
| | |
| <!--Precautions with Alcohol-->
| |
| |alcohol=* Alcohol-Asparaginase interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
| |
| | |
| <!--Brand Names-->
| |
| |brandNames=* Asparaginase®
| |
| | |
| <!--Look-Alike Drug Names-->
| |
| |lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web | last = | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher = | date = }}</ref>
| |
| | |
| <!--Drug Shortage Status-->
| |
| |drugShortage=
| |
| }}
| |
| {{PillImage
| |
| |fileName=No image.jpg
| |
| }}
| |
| {{LabelImage
| |
| |fileName=Asparaginase03.png
| |
| }}
| |
| {{LabelImage
| |
| |fileName=Asparaginase04.png
| |
| }}
| |
| <!--Pill Image-->
| |
| | |
| | |
| | |
| <!--Label Display Image-->
| |
| | |
| | |
| | |
| | |
| | |
| <!--Category-->
| |
| | |
| [[Category:Drug]]
| |