Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase exposure to unconjugated monomethyl auristatin E (MMAE), the anti-mitotic and cytotoxic component of polatuzumab vedotin. MMAE is a substrate for 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. No data are available for other, less potent CYP450 3A4 inhibitors.

MANAGEMENT: Caution is advised when polatuzumab vedotin is used concomitantly with CYP450 3A4 inhibitors. Patients should be 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.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.