Cefotetan

Teratogenic Effects.

Pregnancy Category B.

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.

Reproduction studies have been performed in rats and monkeys at doses up to 2000 and 600 mg/kg/day (3 and 2 times the maximum recommended human dose on a body surface area basis, respectively), and have revealed no evidence of impaired fertility or harm to the fetus due to cefotetan.

Cefotetan is excreted in human milk in very low concentrations. Caution should be exercised when cefotetan is administered to a nursing woman.

Although long-term studies in animals have not been performed to evaluate carcinogenic potential, no mutagenic potential of cefotetan was found in standard laboratory tests.

Cefotetan has adverse affects on the testes of prepubertal rats. Subcutaneous administratio n of 500 mg/kg/day (approximately 0.8 times the maximum adult human dose on a body surface area basis) on days 6 to 35 of life (thought to be developmentally analogous to late childhood and prepuberty in humans) resulted in reduced testicular weight and seminiferous tubule degeneration in 10 of 10 animals. Affected cells included spermatogonia and spermato cytes; Sertoli and Leydig cells were unaffected. Incidence and severity of lesio ns were dosedependant; at 120 mg/kg/day (0.2 times the maximum human dose on a body surface area basis) only 1 of 10 treated animals was affected, and the degree of deg eneration was mild.

Similar lesions have been observed in experiments of co mparable design with other methylthiotetrazole-containing antibiotics and impaired fertility has been reported, particularly at high dose levels. No testicular effects were observed in 7-week-old rats treated with up to 1000 mg/kg/day subcutaneous for 5 weeks, or in infant dogs (3 weeks old) that received up to 300 mg/kg/day intravenous for 5 weeks (both 1.6 times the maximum recommended human dose on a body surface area basis). The relevance of these findings to humans is unknown.

In clinical studies, the following adverse effects were considered related to cefotetan therapy. Those appearing in italics have been reported during postmarketing experience.

Gastrointestinal: symptoms occurred in 1.5% of patients, the mo st frequent were diarrhea (1 in 80) and nausea (1 in 700); pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment or surgical prophylaxis.

Hematologic: laboratory abnormalities occurred in 1.4% of patients and included eosinophilia (1 in 200), positive direct Co o mbs test (1 in 250), and thrombocytosis (1 in 300); agranulocytosis, hemolytic anemia, leukopenia, thrombocytopenia, and prolonged prothrombin time with or without bleeding.

Hepatic: enzyme elevations occurred in 1.2% of patients and included a rise in ALT (SGPT) (1 in 150), AST (SGOT) (1 in 300), alkaline phosphatase (1 in 700), and LDH (1 in 700).

Hypersensitivity: reactions were reported in 1.2% of patients and included rash (1 in 150) and itching (1 in 700); anaphylactic reactions and urticaria.

Local: effects were reported in less than 1% of patients and included phlebitis at the site of injection (1 in 300), and discomfort (1 in 500).

Renal: Elevations in BUN and serum creatinine have been reported.

Urogenital: Nephrotoxicity has rarely been reported.

Miscellaneous: Fever

In addition to the adverse reactions listed above which have been observed in patients treated with cefotetan, the fo llo wing adverse reactions and altered laboratory tests have been reported for cephalo spo rin-class antibiotics: pruritus, Stevens-Johnson syndro me, erythema multiforme, toxic epidermal necro lysis, vomiting, abdominal pain, colitis, superinfection, vaginitis including vaginal candidiasis, renal dysfunction, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemorrhage, elevated bilirubin, pancytopenia, and neutropenia.

Several cephalosporins have been implicated in trigg ering seizures, particularly in patients with renal impairment, when the dosage was not reduced. If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.