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Pregnancy: Risk Summary: TREZILENT is used in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant for pregnancy information.
Based on animal data and mechanism of action, TREZILENT can cause fetal harm when administered to a pregnant woman [see Pharmacology: Mechanism of Action under Actions]. There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, oral administration of alpelisib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes, including embryo-fetal mortality (post-implantation loss), reduced fetal weights, and increased incidences of fetal malformations at maternal exposures ≥ 0.8 times the exposure in humans based on AUC at the recommended dose of 300 mg/day (see Data as follows). Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. However, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies in the U.S. general population.
Data: Animal Data: In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of alpelisib up to 30 mg/kg/day during the period of organogenesis.
In rats, oral administration of alpelisib resulted in maternal toxicity (body weight loss, low food consumption) and no viable fetuses (post-implantation loss) at 30 mg/kg/day (approximately 3 times the exposure in humans at the recommended dose of 300 mg/day based on AUC). At a dose of 10 mg/kg/day (approximately 0.8 times the exposure in humans at the recommended dose of 300 mg/day based on AUC), toxicities included reduced fetal weight and increased incidences of skeletal malformations (bent scapula and thickened or bent long bones) and fetal variations (enlarged brain ventricle, decreased bone ossification).
In a pilot embryo-fetal development study in rabbits, a dose of 30 mg/kg/day resulted in no viable fetuses (post-implantation loss). Doses ≥ 15 mg/kg/day resulted in increased embryo-fetal deaths, reduced fetal weights, and malformations, mostly related to the tail and head. At 15 mg/kg/day in rabbits, the maternal exposure was approximately 5 times the exposure achieved at the recommended human dose of 300 mg/day based on AUC.
Lactation: TREZILENT is used in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant for lactation information.
There is no data on the presence of alpelisib in human milk, its effects on milk production, or the breastfed child. Because of the potential for serious adverse reactions in the breastfed child, advise lactating women to not breastfeed during treatment with TREZILENT and for 1 week after the last dose.
Females and Males of Reproductive Potential: TREZILENT is used in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant for contraception and infertility information.
Pregnancy Testing: Verify the pregnancy status in females of reproductive potential prior to initiating TREZILENT.
Contraception: Females: TREZILENT can cause fetal harm when administered to a pregnant woman [see Pregnancy as previously mentioned]. Advise females of reproductive potential to use effective contraception during treatment with TREZILENT and for 1 week after the last dose.
Males: Advise male patients with female partners of reproductive potential to use condoms and effective contraception during treatment with TREZILENT and for 1 week after the last dose.
Infertility: Based on findings from animal studies, TREZILENT may impair fertility in males and females of reproductive potential [see Pharmacology: Nonclinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility under Actions].
