Drug Interaction Report

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of almotriptan, which is partially metabolized by the isoenzyme. In healthy volunteers, administration of a single 12.5 mg oral dose of almotriptan during treatment with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once a day for 3 days) resulted in approximately 60% increases in almotriptan peak plasma concentration (Cmax) and systemic exposure (AUC). Coadministration with a moderate inhibitor, verapamil (120 mg sustained-release tablets twice a day for 7 days), increased almotriptan Cmax by 24% and AUC by 20%, which are not considered clinically significant.

MANAGEMENT: Caution is advised if almotriptan is used 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. The possibility of prolonged and/or increased pharmacologic effects of almotriptan, including serious adverse effects such as vasospastic reactions, should be considered during concomitant therapy. Patients should be advised to notify their physician if they experience nausea; pain or tightness in the chest, neck, or jaw; irregular heartbeat; abnormal breathing; seizures; tremor; and/or tingling or numbness.

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.