reactions were reported in the postmarketing experience with Kyprolis. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: hemolytic uremic syndrome (HUS), gastrointestinal perforation, pericarditis.
7 DRUG INTERACTIONS
Carfilzomib is primarily metabolized via peptidase and epoxide hydrolase activities, and as a result, the pharmacokinetic profile of carfilzomib is unlikely to be affected by concomitant administration of cytochrome P450 inhibitors and inducers. Carfilzomib is not expected to influence exposure of other drugs [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Kyprolis can cause fetal harm based on findings from animal studies [see Data] and the drug's mechanism of action [see Clinical Pharmacology (12.1)]. There are no adequate and well-controlled studies in pregnant women using Kyprolis.
Females of reproductive potential should be advised to avoid becoming pregnant while being treated with Kyprolis. Males of reproductive potential should be advised to avoid fathering a child while being treated with Kyprolis. Consider the benefits and risks of Kyprolis and possible risks to the fetus when prescribing Kyprolis to a pregnant woman. If Kyprolis is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus. 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. Carfilzomib was not teratogenic at any dose tested. In rabbits, there was an increase in pre-implantation loss at ≥ 0.4 mg/kg/day and an 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 body surface area.
8.2 Lactation
Risk Summary
There is no information regarding the presence of Kyprolis in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Kyprolis and any potential adverse effects on the breastfed infant from Kyprolis or from the underlying maternal condition.
8.3 Females and Males of Reproductive Potential
Contraception
Kyprolis can cause fetal harm [see Use in Specific Populations (8.1)]. Advise female patients of reproductive potential to use effective contraceptive measures or abstain from sexual activity to prevent pregnancy during treatment with Kyprolis and for at least 30 days following completion of therapy. Advise male patients of reproductive potential to use effective contraceptive measures or abstain from sexual activity to prevent pregnancy during treatment with Kyprolis and for at least 90 days following completion of therapy.
8.4 Pediatric Use
The safety and effectiveness of Kyprolis in pediatric patients have not been established.
8.5 Geri |
