Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary Few published case reports with use of polidocanol-containing products, including VARITHENA, in pregnant women have not identified any drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Although no risks have been identified, there is minimal benefit in treating lower extremity varicosities during pregnancy and lower extremity varicosities that develop during pregnancy as they may spontaneously regress postpartum. In animal reproduction studies, no adverse developmental effects were observed with intravenous administration of polidocanol to pregnant rats and rabbits during organogenesis at dose levels up to approximately 13.5 and 12 times, respectively, the proposed maximum human dose of 15 mL of 1% VARITHENA based on body surface area (see Data ) . 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 background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Developmental reproductive toxicity testing was performed in rats and rabbits using intravenous administration of polidocanol solution. In rabbits, dose levels up to and including 10 mg/kg/day (approximately 12 times the proposed maximum human dose of 15 mL of 1% VARITHENA based on body surface area) did not produce any indication of adverse effects on embryo-fetal mortality, fetal weight, or the incidences of fetal abnormalities and variants. In rats administered 27 mg/kg/day of polidocanol solution (approximately 13.5 times the human dose based on body surface area), there were no adverse effects on pregnancy performance or fetal development. In a peri-natal and post-natal study in rats, dose levels of polidocanol up to 9 mg/kg/day (approximately 4.5 times the