Polivy Drug Interactions

No dedicated clinical drug-drug interaction studies with polatuzumab vedotin in humans have been conducted.
Drug interactions with concomitant medicines that are CYP3A4 inhibitors, substrates or inducers and co-medications that are P-gp inhibitors: Based on physiological-based pharmacokinetic (PBPK) model simulations of MMAE released from polatuzumab vedotin, strong CYP3A4 and P-gp inhibitors (e.g., ketoconazole) may increase the area under the concentration-time curve (AUC) of unconjugated MMAE by 48%. Caution is advised in case of concomitant treatment with CYP3A4 inhibitor. Patients receiving concomitant strong CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, cobicistat, indinavir, itraconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) should be monitored more closely for signs of toxicities.
Unconjugated MMAE is not predicted to alter the AUC of concomitant medicines that are CYP3A4 substrates (e.g., midazolam).
Strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenobarbital, phenytoin, St John's wort [Hypericum perforatum]) may decrease the exposure of unconjugated MMAE.
Drug interactions of rituximab, bendamustine, cyclophosphamide, and doxorubicin in combination with polatuzumab vedotin: The pharmacokinetics (PK) of rituximab, bendamustine, cyclophosphamide, and doxorubicin are not affected by co-administration with polatuzumab vedotin. Concomitant rituximab is associated with increased antibody conjugated MMAE (acMMAE) plasma AUC by 24% and decreased unconjugated MMAE plasma AUC by 37%, based on population PK analysis. The plasma AUC of acMMAE and unconjugated MMAE for Polivy plus R-CHP are in line with other studies of Polivy. No dose adjustment is required.
Bendamustine does not affect acMMAE and unconjugated MMAE plasma AUC.