Clobetasol propionate (topical)

8.1 Pregnancy Risk Summary There are no available data on Clobetasol Propionate Cream in pregnant women to inform a drug-associated risk for adverse development outcomes. Published data report a significantly increased risk of low birthweight with the use of greater than 300 grams of potent or very potent topical corticosteroids during a pregnancy. Advise pregnant women of the potential risk to a fetus and to use Clobetasol Propionate Cream on the smallest area of skin and for the shortest duration possible (see Data ).

In animal reproduction studies, increased malformations, such as cleft palate and skeletal abnormalities, were observed after subcutaneous administration of clobetasol propionate to pregnant mice and rabbits. No comparisons of animal exposure with human exposure are provided due to minimal systemic exposure noted after topical administration of Clobetasol Propionate Cream [see Clinical Pharmacology (12.3) ]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk or birth defect loss, or other adverse outcomes. In the U.S.

general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Multiple observational studies found no significant associations between maternal use of topical corticosteroids of any potency and congenital malformations, preterm delivery, or fetal mortality. However, when the dispensed amount of potent or very potent topical corticosteroid exceeded 300 g during the entire pregnancy, use was associated with an increase in low birth weight infants [adjusted RR, 7.74 (95% CI, 1.49-40.11)].

In addition, a small cohort study, in which 28 sub-Saharan women using potent topical corticosteroids (27/28 used clobetasol propionate 0.05%) for skin lightening during pregnancy, noted a higher incidence of low birth weight infants in the exposed group. The majority of exposed subjects treated large areas of the body [a mean quantity of 60 g/month (range, 12-170g)] over long periods of time. Animal Data In an embryofetal development study in mice, subcutaneous administration of clobetasol propionate resulted in fetotoxicity at the highest dose tested ( 1mg/kg) and malformations at the lowest dose tested (0.03 mg/kg). Malformations seen included cleft palate and skeletal abnormalities.

In an embryofetal development study in rabbits, subcutaneous administration of clobetasol propionate resulted in malformations at doses of…