Palifermin Interactions

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary Based on findings in animal studies, Kepivance may cause fetal harm when administered to pregnant women. There are no data available on Kepivance use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, intravenous administration of palifermin to pregnant rabbits and rats during the period of organogenesis resulted in embryo-fetal mortality and alterations to growth [see Data ] . The estimated background risk of major birth defects and miscarriage for the indicated populations 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 2-4% and 15-20%, respectively. Data Animal data In embryo-fetal development studies, palifermin was administered intravenously to pregnant rabbits and rats during the perid of organogenesis. Doses were 5, 60, and 150 μg/kg/day in rabbits (gestation days 6-18) and 100, 300, and 1000 μg/kg/day in rats (gestation days 6 through 17). Increased post-implantation loss and decreased fetal body weights occurred along with maternal toxicity (clinical signs and reductions in body weight gain and food consumption) at doses of 150 μg/kg/day in rabbits and 1000 μg/kg/day in rats. Increased skeletal variations was noted in rats at 1000 μg/kg/day. Doses of 150 μg/kg/day in rabbits and 1000 μg/kg/day in rats are approximately 5-times (rabbits) and 35-times (rats) the exposure (AUC) in patients receiving the recommended dose of 60 μg/kg/day.