Drug Interaction Report

MONITOR CLOSELY: Coadministration with potent inhibitors of CYP450 3A4 may increase 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 ketoconazole, a potent CYP450 3A4 inhibitor, is predicted to increase unconjugated MMAE exposure (AUC) by 45% according to the product labeling. The risk and/or severity of toxicities of polatuzumab vedotin may increase.

MANAGEMENT: Caution is advised when polatuzumab vedotin is used concomitantly with potent CYP450 3A4 inhibitors. Patients should be closely monitored for development or exacerbation of toxicities such as peripheral neuropathy, myelosuppression, opportunistic infections, tumor lysis syndrome and hepatotoxicity, and the dosing of polatuzumab vedotin adjusted or withheld as necessary in accordance with the product labeling.

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.