in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant forpregnancy information.
Based on animal data and mechanism of action, PIQRAY can cause fetal harm when administered to a pregnantwoman [see Clinical Pharmacology (12.1)]. There are no available data in pregnant women to inform the drugassociatedrisk. In animal reproduction studies, oral administration of alpelisib to pregnant rats and rabbits
during organogenesis caused adverse developmental outcomes including embryo-fetal mortality (postimplantationloss), 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). Advisepregnant 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 to30 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 humansat 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 reducedfetal 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 (postimplantationloss). Doses ≥ 15 mg/kg/day resulted in increased embryo-fetal deaths, reduced fetal weights, andmalformations, 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.
8.2 Lactation
PIQRAY is used in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant forlactation information.
There is no data on the presence of alpelisib in human milk, its effects on milk production, or the breastfedchild. Because of the potential for serious adverse reactions in the breastfed child, advise lactating women to notbreastfeed during treatment with PIQRAY and for 1 week after the last dose.
8.3 Females and Males of Reproductive Potential
PIQRAY is used in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant forcontraception and infertility information.
Pregnancy Testing
Verify the pregnancy status in females of reproductive potential prior to initiating PIQRAY.
Contraception
Females
PIQRAY can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Advise females of reproductive potential to use effective contraception during treatment with PIQRAY and for1 week after the last dose.
Males
Advise male patients with female partners o |
