NISOLDIPINE

Fetal Risk Summary

Nisoldipine is a calcium channel blocker indicated for the treatment of hypertension, either alone or in combination with other antihypertensive agents. The elimination half-life (about 7–12 hours) of this agent allows for once-daily dosing.

Animal reproduction studies have been conducted in three different species (1). No teratogenicity was observed in rats and rabbits, but fetotoxicity, most likely due to maternal toxicity, did occur in both species. Decreased fetal weight was observed in pregnant rats given doses about 5 and 16 times the maximum recommended human dose based on body surface area (MRHD). At the higher dose, increased post-implantation loss (resorption) was also noted. In pregnant rabbits, decreased fetal and placental weights occurred at doses approximately 10 times the MRHD. At a dose 30 times the MRHD in pregnant monkeys, the only surviving fetus had forelimb and vertebral abnormalities not previously seen in control monkeys of the same strain (1). In this particular study, control monkeys also had increased rates of abortion and mortality (1).

It is not known if nisoldipine crosses the human placenta. The molecular weight (about 388) is low enough, however, that placental transfer should be expected.

No reports describing the use of nisoldipine during human pregnancy have been located. A 1992 abstract did report the successful use of the agent in 12 women for the treatment of severe postpartum pregnancy-induced hypertension (2). Other calcium channel blockers (e.g., see Nicardipine, Nifedipine, and Verapamil) have been used for maternal hypertension and as tocolytic agents.

Although the lack of human pregnancy data prevents an assessment of the fetal risk, the absence of teratogenicity and the observance of fetotoxicity only at maternal toxic doses is reassuring. Other calcium channel blockers have been extensively used in human pregnancy as antihypertensives and tocolytics without evidence of major congenital defects or fetal toxicity (see Nicardipine, Nifedipine, and Verapamil).

Breast Feeding Summary

No reports describing the use of nisoldipine in human lactation have been reported. The molecular weight (about 388) is low enough that excretion into breast milk should be expected. The effects of this exposure on a nursing infant are unknown. Other calcium channel blockers are excreted in milk and are considered to be compatible with breast feeding by the American Academy of Pediatrics (see Diltiazem, Nifedipine, and Verapamil).

References

1. Product information. Sular. AstraZeneca Pharmaceuticals, 2001.
2. Belfort M. Nisoldipine: preliminary results using a new orally administered calcium antagonist in the treatment of severe postpartum pregnancy induced hypertension(PIH) (abstract). Am J Obstet Gynecol 1992;166:440.