Adcetris Drug Interactions

Interaction with medicinal products metabolised through CYP3A4 route (CYP3A4 inhibitors/inducers): Co-administration of brentuximab vedotin with ketoconazole, a strong CYP3A4 and P-gp inhibitor, increased the exposure to the antimicrotubule agent MMAE by approximately 73%, and did not alter the plasma exposure to brentuximab vedotin. Therefore, co-administration of brentuximab vedotin with strong CYP3A4 and P-gp inhibitors may increase the incidence of neutropenia. If neutropenia develops, refer to Tables 15 & 16 for dosing recommendations for neutropenia (see Dosage & Administration).
Co-administration of brentuximab vedotin with rifampicin, a strong CYP3A4 inducer, did not alter the plasma exposure to brentuximab vedotin. Though PK data are limited, co-administration of rifampicin appeared to reduce plasma concentrations of MMAE metabolites that could be assayed.
Co-administration of midazolam, a CYP3A4 substrate, with brentuximab vedotin did not alter the metabolism of midazolam; therefore, brentuximab vedotin is not expected to alter the exposure to medicines that are metabolized by CYP3A4 enzymes.
Doxorubicin, vinblastine and dacarbazine (AVD): The serum and plasma pharmacokinetic characteristics of antibody drug conjugate (ADC) and MMAE respectively following administration of brentuximab vedotin in combination with AVD were similar to that in monotherapy.
Co-administration of brentuximab vedotin did not affect the plasma exposure of AVD.
Cyclophosphamide, Doxorubicin and Prednisone: The serum and plasma pharmacokinetic characteristics of ADC and MMAE, respectively, following administration of brentuximab vedotin in combination with CHP were similar to that in monotherapy.
Co-administration of brentuximab vedotin is not expected to affect the exposure of CHP.
Bleomycin: There were no formal drug-drug interaction studies with brentuximab vedotin and bleomycin(B). In a phase 1 dose finding and safety study (SGN35-009), unacceptable pulmonary toxicity (including 2 fatal events) was noted in 11 of 25 patients (44%) treated with brentuximab vedotin plus ABVD. No pulmonary toxicity or fatal events were reported with brentuximab vedotin + AVD. Therefore, co-administration of BRENTUXIMAB VEDOTIN (ADCETRIS) with bleomycin is contraindicated (see Contraindications).