Pravachol - Patient Info

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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.

As safety in pregnant women has not been established and there is no apparent benefit to therapy with PRAVACHOL (pravastatin sodium) during pregnancy (see CONTRAINDICA-TIONS), treatment should be immediately discontinued as soon as pregnancy is recognized. PRAVACHOL should be administered to women of child-bearing potential only when such patients are highly unlikely to conceive and have been informed of the potential hazards. Nursing Mothers A small amount of pravastatin is excreted in human breast milk. Because of the potential for serious adverse reactions in nursing infants, women taking PRAVACHOL should not nurse (see CONTRAINDICATIONS).

Pediatric Use

The safety and effectiveness of PRAVACHOL in children and adolescents from 8-18 years of age have been evaluated in a placebo-controlled study of two years duration. Patients treated with pravastatin had an adverse experience profile generally similar to that of patients treated with placebo with influenza and headache commonly reported in both treatment groups. (See ADVERSE REACTIONS: Pediatric Patients.) Doses greater than 40 mg have not been studied in this population. Children and adolescent females of childbearing potential should be counseled on appropriate contraceptive methods while on pravastatin therapy (see CONTRAINDICATIONS and PRECAUTIONS: Pregnancy).

For dosing information see DOSAGE AND ADMINISTRATION: Adult Patients and Pediatric Patients.

Double-blind, placebo-controlled pravastatin studies in children less than 8 years of age have not been conducted.

Geriatric Use

Two secondary prevention trials with pravastatin (CARE and LIPID) included a total of 6,593 sub-jects treated with pravastatin 40 mg for periods ranging up to 6 years. Across these two studies, 36.1% of pravastatin subjects were aged 65 and older and 0.8% were aged 75 and older.

The beneficial effect of pravastatin in elderly subjects in reducing cardiovascular events and in modi-fying lipid profiles was similar to that seen in younger subjects. The adverse event profile in the elderly was similar to that in the overall population. Other reported clinical experience has not identified differences in responses to pravastatin between elderly and younger patients.

Mean pravastatin AUCs are slightly (25-50%) higher in elderly subjects than in healthy young subjects, but mean C max , T max and t values are similar in both age groups and sub-stantial accumulation of pravastatin would not be expected in the elderly (see CLINICAL PHARMACOLOGY: Pharmacokinetics/ Metabolism).