Drug Information for CLARITHROMYCIN (KAISER FOUNDATION HOSPITALS): Carcinogenesis, Mutagenesis, Impairment of Fertility

  • The following in vitro mutagenicity tests have been conducted with clarithromycin:

    Salmonella/Mammalian Microsomes Test

    Bacterial Induced Mutation Frequency Test

    In Vitro Chromosome Aberration Test

    Rat Hepatocyte DNA Synthesis Assay

    Mouse Lymphoma Assay

    Mouse Dominant Lethal Study

    Mouse Micronucleus Test

    All tests had negative results except the In Vitro Chromosome Aberration Test which was weaklypositive in one test and negative in another.

    In addition, a Bacterial Reverse-Mutation Test (Ames Test) has been performed on clarithromycinmetabolites with negative results.

    Fertility and reproduction studies have shown that daily doses of up to 160 mg/kg/day (1.3 times therecommended maximum human dose based on mg/m2) to male and female rats caused no adverseeffects on the estrous cycle, fertility, parturition, or number and viability of offspring. Plasma levels inrats after 150 mg/kg/day were 2 times the human serum levels.

    In the 150 mg/kg/day monkey studies, plasma levels were 3 times the human serum levels. Whengiven orally at 150 mg/kg/day (2.4 times the recommended maximum human dose based on mg/m2),clarithromycin was shown to produce embryonic loss in monkeys. This effect has been attributed tomarked maternal toxicity of the drug at this high dose.

    In rabbits, in utero fetal loss occurred at an intravenous dose of 33 mg/m2, which is 17 times less thanthe maximum proposed human oral daily dose of 618 mg/m2.

    Long-term studies in animals have not been performed to evaluate the carcinogenic potential ofclarithromycin.

  • Drug Information Provided by National Library of Medicine (NLM).