Alitretinoin

8.1 Pregnancy Risk Summary Based on findings in animal studies and its mechanism of action, PANRETIN GEL can cause fetal harm when administered to a pregnant woman. Oral administration of alitretinoin to pregnant animals during the period of organogenesis was teratogenic and embryo lethal at exposures at least 5 times the estimated daily human topical dose ( see Data ). There are no data on the use of PANRETIN GEL in pregnant women. Advise pregnant women of the potential risk to the fetus. 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 Animal Data Oral administration of alitretinoin to pregnant rabbits during the period of organogenesis resulted in early resorptions, post-implantation loss, and fetal defects (limb, craniofacial, fused sternebrae) at doses ≥ 0.5 mg/kg/day (approximately 5 times the estimated daily human topical dose based on body surface area, assuming complete systemic absorption of alitretinoin, when PANRETIN GEL is administered as a 60 g tube over 1 month in a 60 kg human). Early resorptions and post-implantation loss also occurred in rats administered oral alitretinoin at doses ≥5 mg/kg/day (approximately 25 times the estimated daily human topical dose based on body surface area).

Limb and craniofacial defects also occurred in mice administered oral alitretinoin on day 11 of gestation at single doses ≥50 mg/kg (approximately 127 times the estimated daily human topical dose based on body surface area).