Drug Interaction Report

GENERALLY AVOID: Coadministration with inhibitors of CYP450 3A4 may increase exposure to the cytotoxic component of ado-trastuzumab emtansine known as DM1, which has been shown in vitro to be primarily metabolized by CYP450 3A4 and to a lesser extent by CYP450 3A5. No formal drug interaction studies have been conducted. Theoretically, the risk of toxicity may be increased.

MANAGEMENT: The use of ado-trastuzumab emtansine in combination with potent CYP450 3A4 inhibitors such as itraconazole, ketoconazole, posaconazole, voriconazole, conivaptan, nefazodone, cobicistat, delavirdine, protease inhibitors, and ketolide and certain macrolide antibiotics should generally be avoided. Some authorities recommend avoiding concomitant use of ado-trastuzumab emtansine during and for 2 weeks after treatment with itraconazole. Alternative agents with no or minimal CYP450 3A4 inhibitory potential are recommended whenever possible. If no alternatives exist, consider delaying initiation of ado-trastuzumab emtansine until therapy with the potent CYP450 3A4 inhibitor is complete and the drug has cleared from the circulation, or approximately 3 elimination half-lives. When concomitant administration is necessary, patients should be closely monitored for adverse reactions such as hepatic impairment, left ventricular dysfunction, peripheral neuropathy, and thrombocytopenia.

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.