Ripretinib Interactions

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology ( 12.1 )] , QINLOCK can cause fetal harm when administered to a pregnant woman. There are no available data on the use of QINLOCK in pregnant women to inform a drug-associated risk. Administration of ripretinib to pregnant rats and rabbits during the period of organogenesis resulted in malformations primarily associated with the cardiovascular and skeletal systems, anatomic variations, reduced fetal body weight, and increased post-implantation loss at maternal exposures that were approximately equal to the human exposure at the recommended dose of 150 mg (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 In an embryo-fetal development study investigating daily doses of ripretinib administered during the period of organogenesis in rats, ripretinib resulted in malformations primarily associated with the cardiovascular and skeletal systems, including interrupted or retroesophageal aortic arch and retroesophageal subclavian artery, fusion of the exoccipital bone to the first cervical vertebra, branched and fused ribs, anomalies of the cervical, thoracic, caudal, and sacral vertebrae, absent forepaw phalanges, and absent metacarpals at a dose of 20 mg/kg/day (approximately one half of the human exposure at the recommended dose of 150 mg). An increased incidence of anatomic variations were also observed at 20 mg/kg/day. Variations included malpositioned carotid and subclavian artery origins, malpositioned subclavian artery, absent or elongated innominate artery, misshapen and nodulated ribs, bipartite, incompletely ossified, or unossified vertebral centra, small or misshapen vertebral arches, and reductions in ossified forelimb and hindlimb phal