CYP3A4 Inhibitors, Inducers and Substrates: Co-administration of ADCETRIS 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 ADCETRIS. Therefore, co-administration of ADCETRIS with strong CYP3A4 and P-gp inhibitors may increase the incidence of neutropenia. If neutropenia develops, refer to Table 1 or Table 2 on dosing recommendations for neutropenia (see Dosage & Administration). Patients who are receiving strong CYP3A4 inhibitors and P-gp inhibitors concomitantly with ADCETRIS should be closely monitored for adverse events.
Co-administration of ADCETRIS with rifampicin, a strong CYP3A4 inducer, did not alter the plasma exposure to ADCETRIS; however it reduced exposure to MMAE by approximately 31%.
Co-administration of midazolam, a CYP3A4 substrate, with ADCETRIS did not alter the metabolism of midazolam; therefore ADCETRIS is not expected to alter the exposure to medicines that are metabolized by CYP3A4 enzymes.
Doxorubicin, Vinblastine and Dacarbazine: The serum and plasma pharmacokinetic characteristics of ADC and MMAE respectively following administration of ADCETRIS in combination with doxorubicin, vinblastine and dacarbazine were similar to that in monotherapy.
Co-administration of ADCETRIS did not affect the plasma exposure of doxorubicin, vinblastine and dacarbazine.
Cyclophosphamide, Doxorubicin, and Prednisone: The serum and plasma pharmacokinetic characteristics of ADC and MMAE, respectively, following administration of ADCETRIS in combination with cyclophosphamide, doxorubicin, and prednisone were similar to that in monotherapy.
Bleomycin: There were no formal drug-drug interaction studies with brentuximab vedotin and bleomycin. 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 Dosage & Administration).