Timentin Warnings, Precautions, Pregnancy, Nursing, Abuse - Ticarcillin and Clavulanate

Timentin Warnings, Precautions, Pregnancy, Nursing, Abuse - Ticarcillin and Clavulanate

WARNINGS

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 CONCERNING 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.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including Timentin , and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of "antibiotic-associated colitis."

After the diagnosis of pseudomembranous colitis has been established, appropriate therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.

When very high doses of Timentin are administered, especially in the presence of impaired renal function, patients may experience convulsions. (See ADVERSE REACTIONS and OVERDOSAGE.)

General:    While Timentin possesses the characteristic low toxicity of the penicillin group of antibiotics, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic function, is advisable during prolonged therapy.

Bleeding manifestations have occurred in some patients receiving (beta)-lactam antibiotics. These reactions have been associated with abnormalities of coagulation tests such as clotting time, platelet aggregation, and prothrombin time and are more likely to occur in patients with renal impairment.

If bleeding manifestations appear, Timentin treatment should be discontinued and appropriate therapy instituted.

Timentin has only rarely been reported to cause hypokalemia; however, the possibility of this occurring should be kept in mind particularly when treating patients with fluid and electrolyte imbalance. Periodic monitoring of serum potassium may be advisable in patients receiving prolonged therapy.

The theoretical sodium content is 4.75 mEq (109 mg) per gram of Timentin . This should be considered when treating patients requiring restricted salt intake.

As with any penicillin, an allergic reaction, including anaphylaxis, may occur during Timentin administration, particularly in a hypersensitive individual.

The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind, particularly during prolonged treatment. If superinfections occur, appropriate measures should be taken.

Drug/Laboratory Test Interactions:   As with other penicillins, the mixing of Timentin with an aminoglycoside in solutions for parenteral administration can result in substantial inactivation of the aminoglycoside.

Probenecid interferes with the renal tubular secretion of ticarcillin, thereby increasing serum concentrations and prolonging serum half-life of the antibiotic.

High urine concentrations of ticarcillin may produce false-positive protein reactions (pseudoproteinuria) with the following methods: sulfosalicylic acid and boiling test, acetic acid test, biuret reaction and nitric acid test. The bromphenol blue (Multi-stix®) reagent strip test has been reported to be reliable.

The presence of clavulanic acid in Timentin may cause a nonspecific binding of IgG and albumin by red cell membranes leading to a false-positive Coombs test.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals have not been performed to evaluate carcinogenic potential. However, results from assays for gene mutation in vitro using bacteria (Ames tests) and yeast, and for chromosomal effects in vitro in human lymphocytes, and in vivo in mouse bone marrow (micronucleus test) indicate that Timentin is without any mutagenic potential.

Pregnancy (Category B):   Reproduction studies have been performed in rats given doses up to 1050 mg/kg/day 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 this drug 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 or for the treatment of septicemia and/or infections in the pediatric population where the suspected or proven pathogen is Haemophilus influenzae type b.

In those patients in whom meningeal seeding from a distant infection site or in whom meningitis is suspected or documented, or in patients who require prophylaxis against central nervous system infection, an alternate agent with demonstrated clinical efficacy in this setting should be used.