Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary There are no available data on ANDEMBRY use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Monoclonal antibodies such as garadacimab-gxii are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. In an embryo-fetal development study in pregnant rabbits, garadacimab-gxii produced no evidence of fetal harm at doses up to approximately 100 times the exposure achieved at the maximum recommended human dose (MRHD) of 200 mg once monthly. In a pre- and post-natal development study in rabbits, garadacimab-gxii had no effects on survival, growth, or development of F 1 offspring at doses resulting in approximately 76 times the exposure achieved at the MRHD (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population(s) 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 In an embryo-fetal development study in pregnant rabbits dosed by the intravenous route every 3 days during the period of organogenesis from gestation days 6 to 18, garadacimab-gxii produced no evidence of fetal harm or maternal toxicity at doses resulting in approximately 100 times the exposure achieved at the MRHD (on an AUC basis with maternal intravenous doses up to 100 mg/kg/dose). In a pre- and post-natal development study in rabbits dosed by the intravenous or subcutaneous route once every 5 days from the end of implantation (Gestation Day 7) to postpartum day 38 (end of the lactation period), garadacimab-gxii had no effects on survival, growth, or development of F 1 offspr