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 14 and 15 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 metabolised 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 (CHP): 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 ADCETRIS with bleomycin is contraindicated (see Contraindications).