Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary Available data on the use of OJJAARA in pregnant women are insufficient to determine whether there is a drug‑associated risk for major birth defects or miscarriage. Based on animal reproduction studies conducted in rats and rabbits, momelotinib may cause embryo‑fetal toxicity at exposures lower than the expected exposure in patients receiving 200 mg once daily (see Data) . OJJAARA should only be used during pregnancy if the expected benefits to the mother outweigh the potential risks to the fetus. The background risk of major birth defects and miscarriage for the indicated population 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 embryofetal development study, pregnant rats received momelotinib 2, 6 or 12 mg/kg/day orally, during the period of organogenesis (Gestation Day 6 to 17). Embryo‑fetal toxicity (embryonic death, soft tissue anomalies, skeletal variations, and lower mean fetal body weights) was observed at 12 mg/kg (in the presence of maternal toxicity). Skeletal variations were observed (in the absence of maternal toxicity) at 6 mg/kg/day at exposures 3.5 times the exposure at the recommended human dose of 200 mg daily based on combined momelotinib and M21 (a major human metabolite) AUC. No developmental toxicity was observed at 2 mg/kg/day at exposures equivalent to the recommended dose (based on combined momelotinib and M21 AUC). In an embryofetal developmental study, pregnant rabbits received momelotinib at 7.5, 30 or 60 mg/kg/day orally during the period of organogenesis (Gestation Day 7 to 20). Momelotinib was associated with maternal toxicity at 60 mg/kg/day, which resulted in reduced mean fetal weight, delayed bone ossification, and an abortion at less than the exposure