Included as part of the PRECAUTIONS section.

Anaphylactic Reactions

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before initiating therapy with TIMENTIN, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, TIMENTIN should be discontinued and the appropriate therapy instituted. Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management, including intubation, should also be provided as indicated.

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 two 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 [see ADVERSE REACTIONS and OVERDOSAGE].

Risk of Bleeding

Some patients receiving P-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.

Prescribing TIMENTIN either 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) [see DRUG INTERACTIONS].

Clavulanic acid may cause a nonspecific binding of IgG and albumin by red cell membranes, leading to a false-positive Coombs test [see DRUG INTERACTIONS].

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.

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.

Use In Specific Populations

Pregnancy

Teratogenic Effects - 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 on a body surface area basis) and have revealed no evidence of impaired fertility or 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.

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.

Geriatric Use

An analysis of clinical studies of TIMENTIN was conducted to determine whether subjects aged 65 and over 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 [see DOSAGE AND ADMINISTRATION].

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.

Renal Impairment

Ticarcillin is predominantly excreted by the kidney [see CLINICAL PHARMACOLOGY]. Dosage adjustments should be made for patients with renal impairment [see DOSAGE AND ADMINISTRATION].

Last reviewed on RxList: 10/16/2012
This monograph has been modified to include the generic and brand name in many instances.