Pravachol Patient Info

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Pravachol - Patient Info [Pravastatin]

In another 2-year study in mice with doses up to 100 mg/ kg/ day (producing drug exposures approximately 2 times the human dose of 80 mg, based on AUC), there were no drug-induced tumors. No evidence of mutagenicity was observed in vitro, with or without rat-liver metabolic activation, in the following studies: microbial mutagen tests, using mutant strains of Salmonella typhimurium or Escherichia coli; a forward mutation assay in L5178Y TK +/-mouse lymphoma cells; a chromosomal aberration test in hamster cells; and a gene con-version assay using Saccharomyces cerevisiae.

In addition, there was no evidence of mutagenicity in either a dominant lethal test in mice or a micronucleus test in mice. In a study in rats, with daily doses up to 500 mg/ kg, pravastatin did not produce any adverse effects on fertility or general reproductive performance. However, in a study with another HMG-CoA reductase inhibitor, there was decreased fertility in male rats treated for 34 weeks at 25 mg/ kg body weight, although this effect was not observed in a subsequent fer-tility study when this same dose was administered for 11 weeks (the entire cycle of spermato-genesis, including epididymal maturation). In rats treated with this same reductase inhibitor at 180 mg/ kg/ day, seminiferous tubule degeneration (necrosis and loss of spermatogenic epithe-lium) was observed. Although not seen with pravastatin, two similar drugs in this class caused drug-related testicular atrophy, decreased spermatogenesis, spermatocytic degeneration, and giant cell formation in dogs. The clinical significance of these findings is unclear.

Pregnancy Pregnancy Category X.

See CONTRAINDICATIONS. Safety in pregnant women has not been established. Pravastatin was not teratogenic in rats at doses up to 1000 mg/ kg daily or in rabbits at doses of up to 50 mg/ kg daily. These doses resulted in 10X (rabbit) or 120X (rat) the human exposure based on surface area (mg/ meter 2 ). Rare reports of congenital anomalies have been received following intrauterine exposure to other HMG-CoA reductase inhibitors. In a review 9 of approximately 100 prospec-tively followed pregnancies in women exposed to simvastatin or lovastatin, the incidences of congenital anomalies, spontaneous abortions and fetal deaths/ stillbirths did not exceed what would be expected in the general population. The number of cases is adequate only to exclude a three-to-four-fold increase in congenital anomalies over the background incidence. In 89% of the prospectively followed pregnancies, drug treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified.