Tavaborole

8.1 Pregnancy Risk Summary There are no available data on tavaborole topical solution use in pregnant women to inform a drug associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes. In oral animal reproductive studies, administration of tavaborole during the period of organogenesis resulted in embryofetal toxicity and malformations at 570 times the Maximum Recommended Human Dose (MRHD) based on Area Under the Curve (AUC) comparisons in rats and embryofetal toxicity at 155 times the MRHD based on AUC comparisons in rabbits.

Embryofetal toxicity was noted following dermal administration in rabbits up to 36 times the MRHD based on AUC comparisons [ see Data ]. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies carry some risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects in the U.S. general population is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

Data Animal Data Oral administration: In an oral embryofetal development study in rats, oral doses of 30, 100, and 300 mg/kg/day tavaborole were administered during the period of organogenesis (gestational days 6 to 19) to pregnant female rats. In the presence of maternal toxicity, embryofetal toxicity (increased embryofetal resorption and/or deaths) and drug-related skeletal malformations and variations suggestive of delayed development (i.e., a delay in ossification) were noted in fetuses at 300 mg/kg/day tavaborole [570 times the MRHD based on AUC comparisons]. No developmental toxicity was noted in rats at 100 mg/kg/day tavaborole (26 times the MRHD based on AUC comparisons).

In an oral embryofetal development study in rabbits, oral doses of 15, 50, and 150 mg/kg/day tavaborole were administered during the period of organogenesis (gestational days 7 to 19) to pregnant female rabbits. In the presence of maternal toxicity, excessive embryofetal mortality due to post-implantation loss was noted at 150 mg/kg/day tavaborole. No drug related malformations were noted in rabbits at 150 mg/kg/day tavaborole (155 times the MRHD based on AUC comparisons). No embryofetal mortality was noted in rabbits at 50 mg/kg/day tavaborole (16 times the MRHD based on AUC comparisons).

In an oral prenatal and postnatal development study in rats, oral doses of 15, 60, and 100 mg/kg/day tavaborole were administered from the beginning of organogenesis (gestation day 6) through the end of lactation (lactation day 20). In the presence of minimal maternal…