nical Pharmacology (12.3)].
When coadministering TALZENNA with P-gp inhibitors not listed above, monitor patients for potential increased adverse reactions [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)].
Effect of BCRP inhibitors
Coadministration with BCRP inhibitors may increase talazoparib exposure. If coadministration cannot be avoided, monitor patients for potential increased adverse reactions when coadministering [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1)], TALZENNA can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on TALZENNA use in pregnant women to inform a drug-associated risk. In an animal reproduction study, the administration of talazoparib to pregnant rats during the period of organogenesis caused fetal malformations and structural skeletal variations and embryo-fetal death at maternal exposures that were 0.24 times the AUC in patients receiving the recommended dose of 1 mg daily (see Data). Apprise pregnant women and females of reproductive potential of the potential risk to a fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the general U.S. population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
In an embryo-fetal development toxicity study, pregnant rats received oral doses of 0.015, 0.05, and 0.15 mg/kg/day talazoparib during the period of organogenesis. Talazoparib caused embryo-fetal death at doses ≥0.015 mg/kg/day (approximately 0.24 times the AUC in patients at the recommended dose). A dose of 0.015 mg/kg/day caused decreased fetal body weights and an increased incidence of fetal malformations (depressed eye bulge, small eye, split sternebra, and fused cervical vertebral arch) and structural variations including misshapen or incomplete ossification of the sternebra, skull, rib, and vertebra.
8.2 Lactation
Risk Summary
There are no data on the presence of talazoparib in human milk, the effects of the drug on milk production, or the effects of the drug on the breastfed child. Because of the potential for serious adverse reactions in a breastfed child from talazoparib, advise lactating women not to breastfeed during treatment with TALZENNA and for at least 1 month after the final dose.
8.3 Females and Males of Reproductive Potential
Pregnancy Testing
A pregnancy test is recommended for females of reproductive potential prior to initiating TALZENNA treatment.
Contraception
Females
TALZENNA can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of TALZENNA.
Males
Based on genotoxicity and animal reproduction studies, advise male patients with female partners of reproductive potential and pregnant partners to use effective contraception during treatment with TALZENNA and for at least 4 months following the last dose [see Use in Specific Populations (8.1), Nonclinical Toxicology (13.1)].
Infertility
Males
Based on animal studies, TALZENNA may impair fertility in males of |
