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 enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.