Bacrelba Use In Pregnancy & Lactation

Pregnancy: Risk summary: Based on findings from animal studies, Asciminib (Bacrelba) can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies in pregnant women to inform a product-associated risk.
Animal reproduction studies in pregnant rats and rabbits demonstrated that oral administration of asciminib during organogenesis induced embryotoxicity, fetotoxicity and teratogenicity.
Pregnant women and females of reproductive potential should be advised of the potential risk to a fetus if Asciminib (Bacrelba) is used during pregnancy or if the patient becomes pregnant while taking Asciminib (Bacrelba) (see Precautions).
Data: Animal data: In embryo-fetal development studies, pregnant animals received oral doses of asciminib at 25, 150 and 600 mg/kg/day in rats and at 15, 50 and 300 mg/kg/day in rabbits during the period of organogenesis.
In rats, asciminib was not tolerated in maternal animals at 600 mg/kg/day and resulted in the early termination of the dose group. There was no evidence of asciminib-related embryo-fetal death at doses below or equal to 150 mg/kg/day. A dose-related increase in fetal weights at 25 and 150 mg/kg/day was observed. Fetal variations in the urinary tract and skeleton (skull, vertebral column, and ribs), indicative of changes in the rate of development, were observed primarily at 150 mg/kg/day. A slight increase in the malformation rate (anasarca and cardiac malformations) and some visceral variants indicative of adverse effects on embryo-fetal development were also observed at 150 mg/kg/day. The maternal no-observed-adverse-effect level (NOAEL) was 150 mg/kg/day and the fetal NOAEL was 25 mg/kg/day. At the fetal NOAEL of 25 mg/kg/day, the AUC exposures were equivalent to or below those achieved in patients at the 40 mg twice-daily or 80 mg once-daily doses, respectively. At the fetal NOAEL of 25 mg/kg/day, the AUC exposures were below those achieved in patients at the 200 mg twice daily dose.
In rabbits, 300 mg/kg/day caused morbidity in the maternal animals and resulted in the early termination of the dose group. An increased incidence of resorptions, indicative of embryo-fetal mortality, and a low incidence of cardiac malformations, indicative of teratogenicity, were observed at 50 mg/kg/day. There was no effect on fetal growth. The NOAEL for maternal toxicity was 50 mg/kg/day and the fetal NOAEL was 15 mg/kg/day. At the fetal NOAEL of 15 mg/kg/day, the AUC exposures were equivalent to or below those achieved in patients at the 40 mg twice-daily or 80 mg once-daily doses, respectively. At the fetal NOAEL of 15 mg/kg/day, the AUC exposures were below those achieved in patients at the 200 mg twice-daily dose.
Lactation: Risk summary: It is not known if asciminib is transferred into human milk after administration of Asciminib (Bacrelba). There are no data on the effects of asciminib on the breastfed child or on milk production.
Because of the potential for serious adverse drug reactions in the breastfed child, breastfeeding is not recommended during treatment with Asciminib (Bacrelba) and for at least 3 days after the last dose.
Females and males of reproductive potential: Pregnancy testing: The pregnancy status of females of reproductive potential should be verified prior to starting treatment with Asciminib (Bacrelba).
Contraception: Sexually active females of reproductive potential should use effective contraception (methods that result in less than 1% pregnancy rates) during treatment with Asciminib (Bacrelba) and for at least 3 days after the last dose.
Infertility: There are no data on the effect of Asciminib (Bacrelba) on human fertility.
In the rat fertility study, asciminib did not affect reproductive function in male and female rats.
A slight effect on male sperm motility and sperm count was observed at doses of 200 mg/kg/day, likely at AUC exposures 19-fold, 13-fold, or 2-fold higher than those achieved in patients at the 40 mg twice-daily, 80 mg once-daily, or 200 mg twice-daily doses, respectively.