prior to initiating treatment withDAURISMO. Report pregnancy exposures to Pfizer at 1-800-438-1985.
In animal embryo-fetal developmental toxicity studies, repeat-dose oral administration of DAURISMO duringorganogenesis at maternal exposures that were less than the human exposure at the recommended dose resulted in embryotoxicity, fetotoxicity and teratogenicity in rats and rabbits (see Data). Advise pregnant women of the
potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population are unknown.
Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In theU.S. general population, the estimated background risk of major birth defects and miscarriage in clinicallyrecognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
In embryo-fetal developmental toxicity studies, glasdegib was orally administered to pregnant rats and rabbits atdoses up to 100 mg/kg/day during the period of organogenesis. Glasdegib resulted in embryo-fetal lethality(e.g., increased postimplantation loss and decreased numbers of live fetuses) in rats and rabbits at 50 mg/kg/dayand 5 mg/kg/day, respectively, at maternal exposures approximately 4-times and 3-times the human exposure atthe recommended dose [based on Cmax (rat) and AUC (rabbit)]. Doses of ≥ 10 mg/kg in rat [approximately0.6-times the human exposure (Cmax) at the recommended dose] and ≥ 5 mg/kg in rabbit resulted in fetal
developmental abnormalities and malformations consisting of craniofacial malformations, malformed limbs,paws/digits, trunk and tail, dilation of brain,malpositioned/malformed eyes, misshapen head, small tongue,absent palate, teeth and viscera, diaphragmatic hernia, edema, heart defects, rib and vertebral abnormalities,malformed or absent structures in the appendicular skeleton.
8.2 Lactation
Risk Summary
There are no data on the presence of glasdegib or its active metabolites in human milk, the effects of the drug onthe breastfed child, or its effect on milk production. Because of the potential for serious adverse reactions in abreastfed child from DAURISMO, advise women who are taking DAURISMO not to breastfeed or provide
breast milk to infants or children during treatment with DAURISMO and for at least 30 days after the last dose.
8.3 Females and Males of Reproductive Potential
DAURISMO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations(8.1)].
Pregnancy Testing
Conduct pregnancy testing in females of reproductive potential within 7 days prior to initiating therapy withDAURISMO.
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with DAURISMO andat least 30 days after the last dose.
Males
It is not known if glasdegib is present in semen. Advise males of the potential risk of exposure through semenand to use effective contraception, including a condom, even after a vasectomy, to avoid drug exposure to a
pregnant partner or a female partner of reproductive potential during treatment with DAURISMO and for at
least 30 days after the last dose. Advise males to not donate semen during treatment with DAURISMO for at
least 30 days after the last dose [see Nonclinical Toxicology (13.1)].
Infertility
Males
Based on findings in repeat-dose animal toxicity studies in rats, DAURISMO |
