nistration with strong CYP3A inducers [see Clinical Pharmacology (12.3)]. Examplesa of strong CYP3A inducers include: carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, and St. John’s wortb.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
IMBRUVICA, a kinase inhibitor, can cause fetal harm based on findings from animal studies. There are no available data on IMBRUVICA use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, administration of ibrutinib to pregnant rats and rabbits during the period of organogenesis at exposures up to 2-20 times the clinical doses of 420-560 mg daily produced embryofetal toxicity including structural abnormalities (see ANIMAL DATA). If IMBRUVICA is used during pregnancy or if the patient becomes pregnant while taking IMBRUVICA, the patient should be apprised of the potential hazard to the fetus.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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.
Animal Data
Ibrutinib was administered orally to pregnant rats during the period of organogenesis at doses of 10, 40 and 80 mg/kg/day. Ibrutinib at a dose of 80 mg/kg/day was associated with visceral malformations (heart and major vessels) and increased resorptions and post-implantation loss. The dose of 80 mg/kg/day in rats is approximately 14 times the exposure (AUC) in patients with MCL or MZL and 20 times the exposure in patients with CLL/SLL or WM administered the dose of 560 mg daily and 420 mg daily, respectively. Ibrutinib at doses of 40 mg/kg/day or greater was associated with decreased fetal weights. The dose of 40 mg/kg/day in rats is approximately 6 times the exposure (AUC) in patients with MCL administered the dose of 560 mg daily.
Ibrutinib was also administered orally to pregnant rabbits during the period of organogenesis at doses of 5, 15, and 45 mg/kg/day. Ibrutinib at a dose of 15 mg/kg/day or greater was associated with skeletal variations (fused sternebrae) and ibrutinib at a dose of 45 mg/kg/day was associated with increased resorptions and post-implantation loss. The dose of 15 mg/kg/day in rabbits is approximately 2.0 times the exposure (AUC) in patients with MCL and 2.8 times the exposure in patients with CLL/SLL or WM administered the dose of 560 and 420 mg daily, respectively.
8.2 Lactation
Risk Summary
There is no information regarding the presence of ibrutinib or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production.
The development and health benefits of breastfeeding should be considered along with the mother's clinical need for IMBRUVICA and any potential adverse effects on the breastfed child from IMBRUVICA or from the underlying maternal condition.
8.3 Females and Males of Reproductive Potential
Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to initiating IMBRUVICA therapy.
Contraception
Females
Advise females of reproductive potential to avoid pregnancy while taking IMBRUVICA and for up to 1 month after ending treatment. If this drug is used during pregnancy or if the patient becomes pregnant while taking this dr |
