Calcium Channel Blocker
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of clevidipine in human pregnancy have been located. The animal reproduction data suggest risk, but the absence of human pregnancy experience prevents a complete assessment of the embryo–fetal risk. However, other calcium channel blockers have been used extensively in human pregnancy as antihypertensives and tocolytics without evidence of developmental toxicity (e.g., see Nicardipine, Nifedipine, and Verapamil). Nevertheless, until human pregnancy data are available, other agents, such as IV labetalol, are probably preferred to treat severe hypertension in pregnancy if IV therapy is required.
FETAL RISK SUMMARY
Clevidipine is a calcium channel blocker that is given by IV infusion. It is indicated for the reduction of blood pressure when oral therapy is not feasible or desirable. Clevidipine is rapidly metabolized to inactive metabolites. One of the metabolites is formaldehyde. Plasma protein binding is high (>99.5%) and the terminal half-life is very short (about 15 minutes) (1).
Reproduction studies have been conducted in rats and rabbits. In these species, during organogenesis, doses that were 0.7 and 2 times, respectively, the maximum recommended human dose based on BSA (MRHD) decreased fetal survival. Clevidipine crosses the rat placenta. In rats dosed during late gestation and lactation, there were dose-related increases in maternal mortality, length of gestation, and prolonged parturition at doses that were about ≥ 0.17 times the MRHD. When mated, offspring of these dams had a lower conception rate than controls (1).
Long-term animal carcinogenicity studies have not been conducted with clevidipine because of the intended short-term use in humans. Clevidipine was genotoxic in three in vitro assays but not in an in vivo test. The positive in vitro tests were thought likely to be due to the metabolite formaldehyde.
Fertility and mating performance was not affected in male and female rats at doses about equivalent to the MRHD, but female rats demonstrated pseudopregnancy and changes in estrus cycle at doses as low as one-fourth the MRHD.
It is not known if clevidipine crosses the human placenta. The molecular weight (about 456) is low enough, but the rapid metabolism, high plasma protein binding, and a very short terminal half-life suggests that little active drug will cross to the embryo or fetus.
BREASTFEEDING SUMMARY
No reports describing the use of clevidipine during human lactation have been located. The molecular weight (about 456) is low enough, but the rapid metabolism, high plasma protein binding, and a very short terminal half-life suggests that little of the active drug will be excreted into breast milk. Moreover, the drug is given as an IV infusion for hypertension when oral medication is not feasible or desirable. In such cases, it is doubtful if the mother would be nursing a child.
Reference
1.Product information. Cleviprex. The Medicines Company, 2008.