* TIMENTIN® is indicated in the treatment of infections caused by susceptible isolates of the designated bacteria in the conditions listed below:
'''Septicemia'''
* Septicemia (including bacteremia) caused by β‑lactamase–producing isolates of Klebsiella spp.*, Escherichia coli*, Staphylococcus aureus*, or Pseudomonas aeruginosa* (or other Pseudomonas species*)
'''Lower Respiratory Infections'''
* Lower respiratory infections caused by β‑lactamase–producing isolates of S. aureus, Haemophilus influenzae*, or Klebsiella spp.*
'''Bone and Joint Infections'''
* Bone and joint infections caused by β‑lactamase–producing isolates of S. aureus
'''Skin and Skin Structure Infections'''
* Skin and skin structure infections caused by β‑lactamase–producing isolates of S. aureus, Klebsiella spp.*, or E. coli*
'''Urinary Tract Infections'''
* Urinary tract infections (complicated and uncomplicated) caused by β‑lactamase–producing isolates of E. coli, Klebsiella spp., P. aeruginosa* (or other Pseudomonas spp.*), Citrobacter spp.*, Enterobacter cloacae*, Serratia marcescens*, or S. aureus*
:* Dosage
'''Gynecologic Infections'''
=====Condition2=====
* Endometritis caused by β‑lactamase–producing isolates of Prevotella melaninogenicus*, Enterobacter spp. (including E. cloacae*), E. coli, Klebsiella pneumoniae*, S. aureus, or Staphylococcus epidermidis
* Dosing Information
'''Intra-abdominal Infections'''
:* Dosage
* Peritonitis caused by β‑lactamase–producing isolates of E. coli, K. pneumoniae, or Bacteroides fragilis* group
=====Condition3=====
* Efficacy for this organism in this organ system was studied in fewer than 10 infections.
* Dosing Information
* To reduce the development of drug‑resistant bacteria and maintain the effectiveness of TIMENTIN and other antibacterial drugs, TIMENTIN should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
:* Dosage
==Dosage==
=====Condition4=====
* The usual recommended dosage for systemic and urinary tract infections for adults is 3.1 grams of TIMENTIN (3 grams ticarcillin and 100 mg clavulanic acid) given every 4 to 6 hours.
* Dosing Information
* For gynecologic infections, TIMENTIN should be administered as follows (based on ticarcillin content): Moderate infections, 200 mg/kg/day in divided doses every 6 hours; severe infections, 300 mg/kg/day in divided doses every 4 hours.
:* Dosage
* For patients weighing less than 60 kg, the recommended dosage is 200 to 300 mg/kg/day given in divided doses every 4 to 6 hours.
<!--Off-Label Use and Dosage (Adult)-->
* The duration of therapy depends upon the severity of infection. The usual duration is 10 to 14 days; however, in difficult and complicated infections, more prolonged therapy may be required.
<!--Guideline-Supported Use (Adult)-->
==Renal Impairment==
|offLabelAdultGuideSupport======Condition1=====
* Developed by:
For patients with renal insufficiency, an initial loading dose of 3.1 grams should be followed by doses based on creatinine clearance and type of dialysis as indicated in Table 1.
* Class of Recommendation:
[[File:Ticarcillin clavulanate table1.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
* Strength of Evidence:
==DOSAGE FORMS AND STRENGTHS==
* Dosing Information
* The 3.1‑gram glass vial of TIMENTIN for Injection is a white to pale yellow sterile powder for reconstitution containing ticarcillin disodium equivalent to 3 grams ticarcillin and clavulanate potassium equivalent to 0.1 gram clavulanic acid.
:* Dosage
* The 31‑gram Pharmacy Bulk Package of TIMENTIN for Injection is a white to pale yellow sterile powder for reconstitution containing ticarcillin disodium equivalent to 30 grams ticarcillin and clavulanate potassium equivalent to 1 gram clavulanic acid.
=====Condition2=====
* The 100-mL single-dose GALAXY Container (PL 2040 Plastic) of TIMENTIN is a frozen solution containing ticarcillin disodium equivalent to 3.0 grams ticarcillin and clavulanate potassium equivalent to 0.1 gram clavulanic acid.
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
|offLabelAdultGuideSupport=
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport======Condition1=====
|offLabelAdultNoGuideSupport======Condition1=====
Line 110:
Line 129:
<!--Contraindications-->
<!--Contraindications-->
|contraindications=* Condition1
|contraindications=* TIMENTIN is contraindicated in patients who have a history of [[hypersensitivity]] reaction (e.g., [[anaphylaxis]] or [[erythema multiforme]]) to TIMENTIN or to other β‑lactam antibacterials (e.g., penicillins and cephalosporins).
|warnings='''Anaphylactic Reactions'''
<!--Warnings-->
* Serious and occasionally fatal [[hypersensitivity]] (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. Before initiating therapy with TIMENTIN, inquire about previous [[hypersensitivity]] reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, discontinue TIMENTIN and institute appropriate therapy.
|warnings=* Description
====Precautions====
'''Clostridium difficile Associated Diarrhea'''
* Description
* [[Clostridium difficile associated diarrhea]] ([[CDAD]]) has been reported with use of nearly all antibacterial agents, including TIMENTIN, and may range in severity from mild [[diarrhea]] to fatal [[colitis]]. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
<!--Adverse Reactions-->
* C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with [[diarrhea]] following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents.
<!--Clinical Trials Experience-->
* If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
|clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
'''Convulsions'''
* Patients may experience [[convulsions]] when the dose of TIMENTIN exceeds the recommended dose, especially in the presence of impaired renal function.
'''Risk of Bleeding'''
* Some patients receiving β-lactam antibacterials have experienced bleeding associated with abnormalities in coagulation tests. These adverse reactions are more likely to occur in patients with renal impairment. If bleeding manifestations appear, treatment with TIMENTIN should be discontinued and appropriate therapy instituted.
=====Cardiovascular=====
'''Potential for Microbial Overgrowth or Bacterial Resistance'''
* The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy. If superinfections occur, appropriate measures should be taken.
'''Development of Drug-Resistant Bacteria'''
* Prescribing TIMENTIN in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug‑resistant bacteria.
=====Digestive=====
'''Interference with Laboratory Tests'''
* High urine concentrations of ticarcillin may produce false-positive protein reactions (pseudoproteinuria).
* Clavulanic acid may cause a nonspecific binding of IgG and albumin by red cell membranes, leading to a false-positive Coombs test.
'''Electrolyte Imbalance'''
=====Endocrine=====
* [[Hypokalemia]] has been reported during treatment with TIMENTIN. Serum potassium should be monitored in patients with fluid and electrolyte imbalance and in patients receiving prolonged therapy. The theoretical sodium content is 4.51 mEq (103.6 mg) per gram of TIMENTIN. This should be considered when treating patients requiring restricted salt intake.
|clinicalTrials=* The following are discussed in more detail in other sections of the labeling:
:*[[Anaphylactic Reactions]]
:*[[Clostridium difficile Associated Diarrhea]].
'''Clinical Trials Experience'''
=====Hematologic and Lymphatic=====
* Because clinical trials are conducted under widely varying 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.
* Adverse reactions occurring in ≥1% of 867 patients receiving TIMENTIN 3.1 grams in clinical studies included [[rash]], [[nausea]], [[diarrhea]], and [[phlebitis]] at the injection site. The most common laboratory abnormalities (≥3%) were elevations in eosinophils, serum aspartate aminotransferase (AST), and serum alanine aminotransferase (ALT).
* Available safety data for pediatric patients treated with TIMENTIN demonstrate a similar adverse event profile to that observed in adult patients.
|postmarketing=* In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postmarketing use of TIMENTIN. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These adverse reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to TIMENTIN.
:*'''Hypersensitivity Reactions''': Skin [[rash]], [[pruritus]], [[urticaria]], [[arthralgia]], [[myalgia]], drug [[fever]], [[chills]], chest discomfort, [[anaphylactic reactions]], and bullous reactions (including [[erythema multiforme]], [[toxic epidermal necrolysis]], and [[Stevens‑Johnson syndrome]]).
=====Metabolic and Nutritional=====
:*'''Central Nervous System''': [[Headache]], giddiness, neuromuscular hyperirritability, or convulsive [[seizures]].
:*'''Gastrointestinal Disturbances''': Disturbances of taste and smell, [[stomatitis]], [[flatulence]], [[nausea]], [[vomiting]] and [[diarrhea]], [[epigastric pain]], and [[pseudomembranous colitis]] have been reported. Onset of [[pseudomembranous colitis]] symptoms may occur during or after antibacterial treatment.
:* '''Hemic and Lymphatic Systems''': [[Thrombocytopenia]], [[leukopenia]], [[neutropenia]], [[eosinophilia]], reduction of hemoglobin or hematocrit, and prolongation of prothrombin time and bleeding time.
:*'''Abnormalities of Hepatic Function Tests''': Elevation of AST, ALT, serum alkaline phosphatase, serum LDH, and serum bilirubin. There have been reports of transient hepatitis and [[cholestatic jaundice]], as with some other penicillins and some cephalosporins.
=====Musculoskeletal=====
:*'''Renal and Urinary Effects''': Hemorrhagic [[cystitis]], elevation of serum creatinine and/or BUN, [[hypernatremia]], reduction in serum potassium, and uric acid.
:*'''Local Reactions''': [[Pain]], burning, swelling, and induration at the injection site and [[thrombophlebitis]] with intravenous administration.
|drugInteractions='''Aminoglycosides'''
* The mixing of TIMENTIN with an aminoglycoside in solutions for parenteral administration can result in substantial inactivation of the aminoglycoside.
'''Probenecid'''
=====Neurologic=====
* Probenecid interferes with the renal tubular secretion of ticarcillin, thereby increasing serum concentrations and prolonging serum half‑life of ticarcillin. Probenecid does not affect the serum levels of clavulanic acid.
'''Oral Contraceptives'''
* Ticarcillin disodium/clavulanate potassium may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.
'''Effects on Laboratory Tests'''
=====Respiratory=====
* High urine concentrations of ticarcillin may produce false‑positive protein reactions (pseudoproteinuria) with certain methods. The bromphenol blue reagent strip test has been reported to be a reliable method for testing protein reactions.
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Postmarketing Experience-->
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
* Clavulanic acid in TIMENTIN may cause a nonspecific binding of IgG and albumin by red cell membranes, leading to a false‑positive Coombs test. A positive Coombs test should be interpreted with caution during treatment with TIMENTIN
|useInPregnancyFDA='''Pregnancy Category B'''.
* Reproduction studies have been performed in rats given doses up to 1,050 mg/kg/day (approximately half of the recommended human dose based on body surface area) and have revealed no evidence of harm to the fetus due to TIMENTIN. There are, however, no adequate and well‑controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
|useInPregnancyAUS=* There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=* It is not known whether ticarcillin or clavulanic acid is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when TIMENTIN is administered to a nursing woman.
|useInPed=* The safety and effectiveness of TIMENTIN have been established in the age group of 3 months to 16 years. Use of TIMENTIN in these age groups is supported by evidence from adequate and well‑controlled studies of TIMENTIN in adults with additional efficacy, safety, and pharmacokinetic data from both comparative and non‑comparative studies in pediatric patients. There are insufficient data to support the use of TIMENTIN in pediatric patients under 3 months of age.
=====Hematologic and Lymphatic=====
* If meningitis is suspected or documented, an alternative agent with demonstrated clinical efficacy in this setting should be used.
|useInGeri=* An analysis of clinical studies of TIMENTIN was conducted to determine whether subjects aged 65 and older respond differently from younger subjects. Of the 1,078 subjects treated with at least one dose of TIMENTIN, 67.5% were <65 years old, and 32.5% were ≥65 years old. No overall differences in safety or efficacy were observed between older and younger subjects, and other reported clinical experience have not identified differences in responses between the elderly and younger patients, but a greater sensitivity of some older individuals cannot be ruled out.
* This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
* TIMENTIN contains 103.6 mg (4.51 mEq) of sodium per gram of TIMENTIN. At the usual recommended doses, patients would receive between 1,285 and 1,927 mg/day (56 and 84 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important with regard to such diseases as congestive heart failure.
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Drug Interactions-->
|drugInteractions=* Drug
:* Description
<!--Use in Specific Populations-->
|useInPregnancyFDA=* '''Pregnancy Category'''
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
|useInPed=There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
|useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInRenalImpair=Ticarcillin is predominantly excreted by the kidney. Dosage adjustments should be made for patients with renal impairment.
|useInHepaticImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInHepaticImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
|useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
<!--Administration and Monitoring-->
|administration=* Oral
* Intravenous
|administration=* Intravenous
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
* Description
<!--IV Compatibility-->
<!--IV Compatibility-->
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
<!--Overdosage-->
|overdose====Acute Overdose===
====Signs and Symptoms====
|overdose=* In case of overdosage, discontinue TIMENTIN, treat symptomatically, and institute supportive measures as required. Ticarcillin and clavulanic acid may be removed from circulation by hemodialysis.
* Description
====Management====
* Description
===Chronic Overdose===
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
<!--Pharmacology-->
<!--Drug box 2-->
|drugBox=<!--Mechanism of Action-->
|mechAction=*
|mechAction=*
Line 307:
Line 261:
<!--Nonclinical Toxicology-->
<!--Nonclinical Toxicology-->
|nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.
|nonClinToxic='''Carcinogenesis, Mutagenesis, Impairment of Fertility'''
* Long‑term studies in animals have not been performed to evaluate carcinogenic potential. Results from in vitro assays in bacteria (Ames tests), yeast, and human lymphocytes, and in vivo in mouse bone marrow (micronucleus test) indicate TIMENTIN is without genotoxic potential.
* Reproduction studies have been performed in rats given doses up to 1,050 mg/kg/day (approximately half of the recommended human dose based on body surface area) and have revealed no evidence of impaired fertility due to TIMENTIN.
|clinicalStudies=* TIMENTIN has been studied in 296 pediatric patients (excluding neonates and infants less than 3 months) in 6 controlled clinical trials. The majority of patients studied had intra‑abdominal infections, and the primary comparator was clindamycin and gentamicin with or without ampicillin. At the end‑of‑therapy visit, comparable efficacy was reported in the trial arms using TIMENTIN and an appropriate comparator.
<!--Clinical Studies-->
* TIMENTIN was also evaluated in an additional 408 pediatric patients (excluding neonates and infants less than 3 months) in 3 uncontrolled US clinical trials. Patients had a broad range of presenting diagnoses including: Infections in bone and joint, skin and skin structure, lower respiratory tract, urinary tract, as well as intra‑abdominal and gynecologic infections. Patients received TIMENTIN, either 300 mg/kg/day (based on the ticarcillin component) divided every 4 hours for severe infection or 200 mg/kg/day (based on the ticarcillin component) divided every 6 hours for mild to moderate infections. Efficacy rates were comparable to those obtained in controlled trials.
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
<!--How Supplied-->
* The adverse event profile in these 704 pediatric patients treated with TIMENTIN was comparable to that seen in adult patients.
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Overview
Ticarcillin-Clavulanate is a {{{drugClass}}} that is FDA approved for the treatment of {{{indication}}}. Common adverse reactions include .
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indications
TIMENTIN® is indicated in the treatment of infections caused by susceptible isolates of the designated bacteria in the conditions listed below:
Septicemia
Septicemia (including bacteremia) caused by β‑lactamase–producing isolates of Klebsiella spp.*, Escherichia coli*, Staphylococcus aureus*, or Pseudomonas aeruginosa* (or other Pseudomonas species*)
Lower Respiratory Infections
Lower respiratory infections caused by β‑lactamase–producing isolates of S. aureus, Haemophilus influenzae*, or Klebsiella spp.*
Bone and Joint Infections
Bone and joint infections caused by β‑lactamase–producing isolates of S. aureus
Skin and Skin Structure Infections
Skin and skin structure infections caused by β‑lactamase–producing isolates of S. aureus, Klebsiella spp.*, or E. coli*
Urinary Tract Infections
Urinary tract infections (complicated and uncomplicated) caused by β‑lactamase–producing isolates of E. coli, Klebsiella spp., P. aeruginosa* (or other Pseudomonas spp.*), Citrobacter spp.*, Enterobacter cloacae*, Serratia marcescens*, or S. aureus*
Gynecologic Infections
Endometritis caused by β‑lactamase–producing isolates of Prevotella melaninogenicus*, Enterobacter spp. (including E. cloacae*), E. coli, Klebsiella pneumoniae*, S. aureus, or Staphylococcus epidermidis
Intra-abdominal Infections
Peritonitis caused by β‑lactamase–producing isolates of E. coli, K. pneumoniae, or Bacteroides fragilis* group
Efficacy for this organism in this organ system was studied in fewer than 10 infections.
To reduce the development of drug‑resistant bacteria and maintain the effectiveness of TIMENTIN and other antibacterial drugs, TIMENTIN should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Dosage
The usual recommended dosage for systemic and urinary tract infections for adults is 3.1 grams of TIMENTIN (3 grams ticarcillin and 100 mg clavulanic acid) given every 4 to 6 hours.
For gynecologic infections, TIMENTIN should be administered as follows (based on ticarcillin content): Moderate infections, 200 mg/kg/day in divided doses every 6 hours; severe infections, 300 mg/kg/day in divided doses every 4 hours.
For patients weighing less than 60 kg, the recommended dosage is 200 to 300 mg/kg/day given in divided doses every 4 to 6 hours.
The duration of therapy depends upon the severity of infection. The usual duration is 10 to 14 days; however, in difficult and complicated infections, more prolonged therapy may be required.
Renal Impairment
For patients with renal insufficiency, an initial loading dose of 3.1 grams should be followed by doses based on creatinine clearance and type of dialysis as indicated in Table 1.
This image is provided by the National Library of Medicine.
DOSAGE FORMS AND STRENGTHS
The 3.1‑gram glass vial of TIMENTIN for Injection is a white to pale yellow sterile powder for reconstitution containing ticarcillin disodium equivalent to 3 grams ticarcillin and clavulanate potassium equivalent to 0.1 gram clavulanic acid.
The 31‑gram Pharmacy Bulk Package of TIMENTIN for Injection is a white to pale yellow sterile powder for reconstitution containing ticarcillin disodium equivalent to 30 grams ticarcillin and clavulanate potassium equivalent to 1 gram clavulanic acid.
The 100-mL single-dose GALAXY Container (PL 2040 Plastic) of TIMENTIN is a frozen solution containing ticarcillin disodium equivalent to 3.0 grams ticarcillin and clavulanate potassium equivalent to 0.1 gram clavulanic acid.
Off-Label Use and Dosage (Adult)
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Ticarcillin-Clavulanate in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding FDA-Labeled Use of Ticarcillin-Clavulanate in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Ticarcillin-Clavulanate in pediatric patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Ticarcillin-Clavulanate in pediatric patients.
Contraindications
TIMENTIN is contraindicated in patients who have a history of hypersensitivity reaction (e.g., anaphylaxis or erythema multiforme) to TIMENTIN or to other β‑lactam antibacterials (e.g., penicillins and cephalosporins).
Warnings
Anaphylactic Reactions
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. Before initiating therapy with TIMENTIN, inquire about previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, discontinue TIMENTIN and institute appropriate therapy.
Clostridium difficile Associated Diarrhea
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including TIMENTIN, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Convulsions
Patients may experience convulsions when the dose of TIMENTIN exceeds the recommended dose, especially in the presence of impaired renal function.
Risk of Bleeding
Some patients receiving β-lactam antibacterials have experienced bleeding associated with abnormalities in coagulation tests. These adverse reactions are more likely to occur in patients with renal impairment. If bleeding manifestations appear, treatment with TIMENTIN should be discontinued and appropriate therapy instituted.
Potential for Microbial Overgrowth or Bacterial Resistance
The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy. If superinfections occur, appropriate measures should be taken.
Development of Drug-Resistant Bacteria
Prescribing TIMENTIN in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug‑resistant bacteria.
Interference with Laboratory Tests
High urine concentrations of ticarcillin may produce false-positive protein reactions (pseudoproteinuria).
Clavulanic acid may cause a nonspecific binding of IgG and albumin by red cell membranes, leading to a false-positive Coombs test.
Electrolyte Imbalance
Hypokalemia has been reported during treatment with TIMENTIN. Serum potassium should be monitored in patients with fluid and electrolyte imbalance and in patients receiving prolonged therapy. The theoretical sodium content is 4.51 mEq (103.6 mg) per gram of TIMENTIN. This should be considered when treating patients requiring restricted salt intake.
Adverse Reactions
Clinical Trials Experience
The following are discussed in more detail in other sections of the labeling:
Because clinical trials are conducted under widely varying 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.
Adverse reactions occurring in ≥1% of 867 patients receiving TIMENTIN 3.1 grams in clinical studies included rash, nausea, diarrhea, and phlebitis at the injection site. The most common laboratory abnormalities (≥3%) were elevations in eosinophils, serum aspartate aminotransferase (AST), and serum alanine aminotransferase (ALT).
Available safety data for pediatric patients treated with TIMENTIN demonstrate a similar adverse event profile to that observed in adult patients.
Postmarketing Experience
In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postmarketing use of TIMENTIN. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These adverse reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to TIMENTIN.
Abnormalities of Hepatic Function Tests: Elevation of AST, ALT, serum alkaline phosphatase, serum LDH, and serum bilirubin. There have been reports of transient hepatitis and cholestatic jaundice, as with some other penicillins and some cephalosporins.
Renal and Urinary Effects: Hemorrhagic cystitis, elevation of serum creatinine and/or BUN, hypernatremia, reduction in serum potassium, and uric acid.
Local Reactions: Pain, burning, swelling, and induration at the injection site and thrombophlebitis with intravenous administration.
Drug Interactions
Aminoglycosides
The mixing of TIMENTIN with an aminoglycoside in solutions for parenteral administration can result in substantial inactivation of the aminoglycoside.
Probenecid
Probenecid interferes with the renal tubular secretion of ticarcillin, thereby increasing serum concentrations and prolonging serum half‑life of ticarcillin. Probenecid does not affect the serum levels of clavulanic acid.
Oral Contraceptives
Ticarcillin disodium/clavulanate potassium may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.
Effects on Laboratory Tests
High urine concentrations of ticarcillin may produce false‑positive protein reactions (pseudoproteinuria) with certain methods. The bromphenol blue reagent strip test has been reported to be a reliable method for testing protein reactions.
Clavulanic acid in TIMENTIN may cause a nonspecific binding of IgG and albumin by red cell membranes, leading to a false‑positive Coombs test. A positive Coombs test should be interpreted with caution during treatment with TIMENTIN
Reproduction studies have been performed in rats given doses up to 1,050 mg/kg/day (approximately half of the recommended human dose based on body surface area) and have revealed no evidence of harm to the fetus due to TIMENTIN. There are, however, no adequate and well‑controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Ticarcillin-Clavulanate in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Ticarcillin-Clavulanate during labor and delivery.
Nursing Mothers
It is not known whether ticarcillin or clavulanic acid is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when TIMENTIN is administered to a nursing woman.
Pediatric Use
The safety and effectiveness of TIMENTIN have been established in the age group of 3 months to 16 years. Use of TIMENTIN in these age groups is supported by evidence from adequate and well‑controlled studies of TIMENTIN in adults with additional efficacy, safety, and pharmacokinetic data from both comparative and non‑comparative studies in pediatric patients. There are insufficient data to support the use of TIMENTIN in pediatric patients under 3 months of age.
If meningitis is suspected or documented, an alternative agent with demonstrated clinical efficacy in this setting should be used.
Geriatic Use
An analysis of clinical studies of TIMENTIN was conducted to determine whether subjects aged 65 and older respond differently from younger subjects. Of the 1,078 subjects treated with at least one dose of TIMENTIN, 67.5% were <65 years old, and 32.5% were ≥65 years old. No overall differences in safety or efficacy were observed between older and younger subjects, and other reported clinical experience have not identified differences in responses between the elderly and younger patients, but a greater sensitivity of some older individuals cannot be ruled out.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
TIMENTIN contains 103.6 mg (4.51 mEq) of sodium per gram of TIMENTIN. At the usual recommended doses, patients would receive between 1,285 and 1,927 mg/day (56 and 84 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important with regard to such diseases as congestive heart failure.
Gender
There is no FDA guidance on the use of Ticarcillin-Clavulanate with respect to specific gender populations.
Race
There is no FDA guidance on the use of Ticarcillin-Clavulanate with respect to specific racial populations.
Renal Impairment
Ticarcillin is predominantly excreted by the kidney. Dosage adjustments should be made for patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Ticarcillin-Clavulanate in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Ticarcillin-Clavulanate in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Ticarcillin-Clavulanate in patients who are immunocompromised.
Administration and Monitoring
Administration
Intravenous
Monitoring
There is limited information regarding Monitoring of Ticarcillin-Clavulanate in the drug label.
IV Compatibility
There is limited information regarding IV Compatibility of Ticarcillin-Clavulanate in the drug label.
Overdosage
In case of overdosage, discontinue TIMENTIN, treat symptomatically, and institute supportive measures as required. Ticarcillin and clavulanic acid may be removed from circulation by hemodialysis.
Pharmacology
There is limited information regarding Ticarcillin-Clavulanate Pharmacology in the drug label.
There is limited information regarding Pharmacodynamics of Ticarcillin-Clavulanate in the drug label.
Pharmacokinetics
There is limited information regarding Pharmacokinetics of Ticarcillin-Clavulanate in the drug label.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long‑term studies in animals have not been performed to evaluate carcinogenic potential. Results from in vitro assays in bacteria (Ames tests), yeast, and human lymphocytes, and in vivo in mouse bone marrow (micronucleus test) indicate TIMENTIN is without genotoxic potential.
Reproduction studies have been performed in rats given doses up to 1,050 mg/kg/day (approximately half of the recommended human dose based on body surface area) and have revealed no evidence of impaired fertility due to TIMENTIN.
Clinical Studies
TIMENTIN has been studied in 296 pediatric patients (excluding neonates and infants less than 3 months) in 6 controlled clinical trials. The majority of patients studied had intra‑abdominal infections, and the primary comparator was clindamycin and gentamicin with or without ampicillin. At the end‑of‑therapy visit, comparable efficacy was reported in the trial arms using TIMENTIN and an appropriate comparator.
TIMENTIN was also evaluated in an additional 408 pediatric patients (excluding neonates and infants less than 3 months) in 3 uncontrolled US clinical trials. Patients had a broad range of presenting diagnoses including: Infections in bone and joint, skin and skin structure, lower respiratory tract, urinary tract, as well as intra‑abdominal and gynecologic infections. Patients received TIMENTIN, either 300 mg/kg/day (based on the ticarcillin component) divided every 4 hours for severe infection or 200 mg/kg/day (based on the ticarcillin component) divided every 6 hours for mild to moderate infections. Efficacy rates were comparable to those obtained in controlled trials.
The adverse event profile in these 704 pediatric patients treated with TIMENTIN was comparable to that seen in adult patients.
How Supplied
Storage
There is limited information regarding Ticarcillin-Clavulanate Storage in the drug label.
Images
Drug Images
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