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.