Tabrecta Use In Pregnancy & Lactation

Pregnancy: Risk Summary: Based on findings from animal studies and its mechanism of action (see Pharmacology: Pharmacodynamics under Actions), Tabrecta can cause fetal harm when administered to a pregnant woman. There are no available data on Tabrecta use in pregnant women. Oral administration of capmatinib to pregnant rats and rabbits during the period of organogenesis resulted in malformations at maternal exposures less than the human exposure based on AUC at the 400 mg twice daily clinical dose (see Data as follows). Advise pregnant women of the potential risk to a fetus.
Data: Animal Data: In rats, maternal toxicity (reduced body weight gain and food consumption) occurred at 30 mg/kg/day (approximately 1.4 times the human exposure based on AUC at the 400 mg twice daily clinical dose). Fetal effects included reduced fetal weights, irregular/incomplete ossification, and increased incidences of fetal malformations (e.g., abnormal flexure/inward malrotation of hindpaws/forepaws, thinness of forelimbs, lack of/reduced flexion at the humerus/ulna joints, and narrowed or small tongue) at doses of ≥ 10 mg/kg/day (approximately 0.6 times the human exposure based on AUC at the 400 mg twice daily clinical dose).
In rabbits, no maternal effects were detected at doses up to 60 mg/kg/day (approximately 1.5 times the human exposure based on AUC at the 400 mg twice daily clinical dose). Fetal effects included small lung lobe at ≥ 5 mg/kg/day (approximately 0.016 times the human exposure based on AUC at the 400 mg twice daily clinical dose), and reduced fetal weights, irregular/incomplete ossification and increased incidences of fetal malformations (e.g., abnormal flexure/malrotation of hindpaws/forepaws, thinness of forelimbs/hindlimbs, lack of/reduced flexion at the humerus/ulna joints, small lung lobes, narrowed or small tongue) at the dose of 60 mg/kg/day.
Lactation: Risk Summary: There are no data on the presence of capmatinib or its metabolites in either human or animal milk or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Tabrecta and for 1 week after the last dose.
Females and Males of Reproductive Potential: Based on animal data, Tabrecta can cause malformations at doses less than the human exposure based on AUC at the 400 mg twice daily clinical dose (see Data as previously mentioned).
Pregnancy Testing: Verify pregnancy status for females of reproductive potential prior to starting treatment with Tabrecta.
Contraception: Females: Advise females of reproductive potential to use effective contraception during treatment with Tabrecta and for 1 week after the last dose.
Males: Advise males with female partners of reproductive potential to use effective contraception during treatment with Tabrecta and for 1 week after the last dose.