Kyprolis Use In Pregnancy & Lactation

Pregnancy: Risk Summary: Kyprolis can cause fetal harm based on findings from animal studies and its mechanism of action [see Pharmacology: Mechanism of Action under Actions]. There are no available data on Kyprolis use in pregnant women to evaluate for drug-associated risks. Kyprolis caused embryo-fetal lethality in rabbits at doses lower than the clinical dose (see Data as follows). Advise pregnant women of the potential risk to the fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.
Data: Animal Data: Carfilzomib administered intravenously to pregnant rats and rabbits during the period of organogenesis was not teratogenic at doses up to 2 mg/kg/day in rats and 0.8 mg/kg/day in rabbits. In rabbits, there was an increase in pre-implantation loss at ≥ 0.4 mg/kg/day andan increase in early resorptions and post-implantation loss and a decrease in fetal weight at the maternally toxic dose of 0.8 mg/kg/day. The doses of 0.4 and 0.8 mg/kg/day in rabbits are approximately 20% and 40%, respectively, of the recommended dose in humans of 27 mg/m² based on BSA.
Lactation: Risk Summary: There are no data on the presence of Kyprolis in human milk, the effects on the breastfed child, or the effects of the drug on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with Kyprolis and for 2 weeks after treatment.
Females and Males of Reproductive Potential: Based on its mechanism of action and findings in animals, Kyprolis can cause fetal harm when administered to a pregnant woman [see Pregnancy as previously mentioned].
Pregnancy Testing: Conduct pregnancy testing on females of reproductive potential prior to initiating Kyprolis treatment.
Contraception: Females: Advise females of reproductive potential to use effective contraception during treatment with Kyprolis and for at least 6 months following the final dose.
Males: Advise males with female sexual partners of reproductive potential to use effective contraception during treatment with Kyprolis and for at least 3 months following the final dose.
Infertility: Based on the mechanism of action, Kyprolis may have an effect on either male or female fertility [see Pharmacology: Mechanism of Action under Actions and Pharmacology: Toxicology: Nonclinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility under Actions]. There are no data on the effect of Kyprolis on human fertility.