⛔ FDA Black Box Warning
WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS [see Warnings and Precautions (5.9) , Adverse Reactions (6.1) ] . WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) See full prescribing information for complete boxed warning. JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS ( 5.9 , 6.1 ).
Contraindications
4 CONTRAINDICATIONS ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation) [see Adverse Reactions (6.1) ] . Concomitant use with bleomycin due to pulmonary toxicity (4) .
Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary ADCETRIS can cause fetal harm based on the findings from animal studies and the drug’s mechanism of action [see Clinical Pharmacology (12.1) ] . In animal reproduction studies, administration of brentuximab vedotin to pregnant rats during organogenesis at doses similar to the clinical dose of 1.8 mg/kg every three weeks caused embryo-fetal toxicities, including congenital malformations (see Data ). The available data from case reports on ADCETRIS use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. Advise a pregnant woman of the potential risk to a 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 In an embryo-fetal developmental study, pregnant rats received 2 intravenous doses of 0.3, 1, 3, or 10 mg/kg brentuximab vedotin during the period of organogenesis (once each on Pregnancy Days 6 and 13). Drug-induced embryo-fetal toxicities were seen mainly in animals treated with 3 and 10 mg/kg of the drug and included increased early resorption (≥99%), post-implantation loss (≥99%), decreased numbers of live fetuses, and external malformations (i.e., umbilical hernias and malrotated hindlimbs). Systemic exposure in animals at the brentuximab vedotin dose of 3 mg/kg is approximately the same exposure in patients with cHL or sALCL who received the recommended dose of 1.8 mg/kg every three weeks.