Drug Interactions between amoxicillin / clarithromycin / vonoprazan and polatuzumab vedotin

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.

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.

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.