Nisoldipine

Category C.

Nisoldipine was neither teratogenic nor fetotoxic at doses that were not maternally toxic. Nisoldipine was fetotoxic but not teratogenic in rats and rabbits at doses resulting in maternal toxicity (reduced maternal body weight gain). In pregnant rats, increased fetal resorption (postimplantation loss) was observed at 100 mg/kg/day and decreased fetal weight was observed at both 30 and 100 mg/kg/day. These doses are, respectively, about 5 and 16 times the MRHD when compared on a mg/m² basis. In pregnant rabbits, decreased fetal and placental weights were observed at a dose of 30 mg/kg/day, about 10 times the MRHD when compared on a mg/m² basis. In a study in which pregnant monkeys (both treated and control) had high rates of abortion and mortality, the only surviving fetus from a group exposed to a maternal dose of 100 mg nisoldipine/kg/day (about 30 times the MRHD when compared on a mg/m² basis) presented with forelimb and vertebral abnormalities not previously seen in control monkeys of the same strain. There are no adequate and well controlled studies in pregnant women. Nisoldipine should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether nisoldipine is excreted in human milk. Because many drugs are excreted in human milk, a decision should be made to discontinue nursing, or to discontinue nisoldipine, taking into account the importance of the drug to the mother.

Dietary administration of nisoldipine to male and female rats for up to 24 months (mean doses up to 82 and 111 mg/kg/day, 16 and 19 times the maximum recommended human dose [MRHD] on a mg/m² basis, respectively) and female mice for up to 21 months (mean doses of up to 217 mg/kg/day, 20 times the MRHD on a mg/m² basis) revealed no evidence of tumorigenic effect of nisoldipine. In male mice receiving a mean dose of 163 mg nisoldipine/kg/day (16 times the MRHD of 60 mg/day on a mg/m² basis), an increased frequency of stomach papilloma, but still within the historical range, was observed. No evidence of stomach neoplasia was observed at lower doses (up to 58 mg/kg/day). Nisoldipine was negative when tested in a battery of genotoxicity assays including the Ames test and the CHO/HGRPT assay for mutagenicity and the in vivo mouse micronucleus test and in vitro CHO cell test for clastogenicity.

When administered to male and female rats at doses of up to 30 mg/kg/day (about 5 times the MRHD on a mg/m² basis) nisoldipine had no effect on fertility.