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.

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: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.