Drug Interaction Report

Coadministration with potent inducers of CYP450 3A4 may decrease exposure to unconjugated monomethyl auristatin E (MMAE), the anti-mitotic and cytotoxic component of polatuzumab vedotin. Polatuzumab vedotin is an antibody-drug conjugate (ADC) that releases MMAE via proteolytic cleavage, and MMAE has been shown in vitro to be primarily metabolized by CYP450 3A4. Concomitant use of polatuzumab vedotin with rifampin, a potent CYP450 3A4 inducer, is predicted to decrease unconjugated MMAE exposure (AUC) by 63% according to the product labeling. However, the clinical relevance is unknown, since the intact ADC containing the antibody component is required to bind to CD79b, the specific surface protein found on B cell receptors, which allows for internalization and cleavage by lysosomal proteases to enable intracellular delivery of MMAE.