Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ], HERNEXEOS can cause fetal harm when administered to a pregnant woman. There are no available data on the use of HERNEXEOS in pregnant women to inform a drug-associated risk. Oral administration of zongertinib to pregnant rats during the period of organogenesis caused structural abnormalities and alterations to growth at maternal exposures ≥ 19 times the human exposure based on AUC at the recommended dose [see Data ] . Advise pregnant women and females of reproductive potential of the potential risk to a 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 In an embryo-fetal development study, pregnant rats received oral doses of 10, 30, or 60 mg/kg/day of zongertinib during the period of organogenesis (gestation day 7 to 18). Zongertinib caused decreased fetal weights, delayed development of the urinary system, and kidney hydronephrosis at 60 mg/kg/day (approximately 19 times the human exposure based on AUC at the recommended dose). In an embryo-fetal development study in rabbits, there were no adverse embryo-fetal findings in pregnant animals administered oral doses of zongertinib up to 120 mg/kg/day (2.4 times the human exposure based on AUC at the recommended dose) during the period of organogenesis (gestation day 6 to 19). A literature-based assessment of the effects on reproduction demonstrated that mice expressing catalytically inactive HER2 die at mid-gestation due to cardiac dysfunction.