Ziftomenib Interactions

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary Based on findings in animals and its mechanism of action [see Clinical Pharmacology ( 12.1 )] , KOMZIFTI can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on KOMZIFTI use in pregnant women to evaluate for a drug-associated risk. In animal reproduction studies, oral administration of ziftomenib to pregnant mice during the period of organogenesis resulted in adverse developmental outcomes, including embryo-fetal mortality, structural abnormalities, and altered fetal growth at maternal exposures approximately 0.3 times the human exposure (AUC) at the recommended dose (see Data ) . Advise pregnant women 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 Ziftomenib was administered orally twice daily to pregnant mice at doses of 6, 20, and 60 mg/kg/day during organogenesis (gestation days 6-15). Decreased fetal body weight, embryo-fetal lethality, fetal external and skeletal malformations and variations (cleft palate, fused cervical arches, absent lumbar vertebrae fused and/or misaligned costal cartilage, absent or short rib, supernumerary site in the suture bone or split palatine of the skull, and/or fused, unossified, and/or incompletely ossified sternebrae) were noted at all doses. At the dose of 6 mg/kg/day in mice, the maternal exposure was approximately 0.3 times the human exposure at the recommended dose of 600 mg once daily.