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.

ADJUST DOSING INTERVAL: Food may reduce the systemic bioavailability of amprenavir from fosamprenavir oral suspension. The mechanism of interaction has not been described. According to the product labeling, administration of fosamprenavir oral suspension (1400 mg single dose) with a high-fat meal (967 kcal, 67 g fat, 33 g protein, 58 g carbohydrate) reduced amprenavir peak plasma concentration (Cmax) by 46% and systemic exposure (AUC) by 28% compared to administration in a fasted state. The time to reach peak plasma level (Tmax) was delayed by 0.72 hours. In contrast, the same high-fat meal did not affect the pharmacokinetics of amprenavir from fosamprenavir tablets.

MANAGEMENT: Fosamprenavir suspension should be administered on an empty stomach in adults, but with food in pediatric patients to aid palatability and compliance. If emesis occurs within 30 minutes after dosing the suspension, the dose should be repeated. Fosamprenavir tablets may be taken with or without food.