Clotrimazole and betamethasone dipropionate

8.1 Pregnancy Risk Summary There are no available data on topical betamethasone dipropionate or clotrimazole use in pregnant women to identify a clotrimazole and betamethasone dipropionate cream, 1%/0.05% (base) associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Observational studies suggest an increased risk of low birthweight infants with the use of potent or very potent topical corticosteroid during pregnancy .

Advise pregnant women that clotrimazole and betamethasone dipropionate cream, 1%/0.05% (base)may increase the risk of having a low birthweight infant and to use clotrimazole and betamethasone dipropionate cream, 1%/0.05% (base) on the smallest area of skin and for the shortest duration possible. There have been no reproduction studies performed in animals or humans with the combination of clotrimazole and betamethasone dipropionate. In an animal reproduction study, betamethasone dipropionate caused malformations (i.e., umbilical hernias, cephalocele, and cleft palate) in pregnant rabbits when given by the intramuscular route during organogenesis [see Data].

The available data do not allow the calculation of relevant comparisons between the systemic exposure of clotrimazole and/or betamethasone dipropionate observed in the animal studies to the systemic exposure that would be expected in humans after topical use of clotrimazole and betamethasone dipropionate cream, 1%/0.05% (base). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data Animal Data Clotrimazole Studies in pregnant rats treated during organogenesis with intravaginal doses up to 100 mg/kg/day revealed no evidence of fetotoxicity due to clotrimazole exposure. No increase in fetal malformations was noted in pregnant rats receiving oral (gastric tube) clotrimazole doses up to 100 mg/kg/day during gestation Days 6 to 15. However, clotrimazole dosed at 100 mg/kg/day was embryotoxic (increased resorptions), fetotoxic (reduced fetal weights), and maternally toxic (reduced body weight gain) to rats. Clotrimazole dosed at 200 mg/kg/day was maternally lethal, and therefore, fetuses were not evaluated in this group.

Also in this study, doses up to 50 mg/kg/day had no adverse effects on dams or fetuses. However, in the combined fertility,…