Drug Interaction Report

GENERALLY AVOID: Coadministration with potent or moderate inhibitors of CYP450 3A4 may increase the plasma concentrations of aprepitant, which is primarily metabolized by the isoenzyme. According to the manufacturer, administration of a single 125 mg dose of aprepitant on day 5 of treatment with the potent CYP450 3A4 inhibitor ketoconazole (400 mg/day for 10 days) resulted in a 5-fold increase in mean aprepitant systemic exposure (AUC) and a 3-fold increase in mean terminal half-life. In patients with mild to moderate hypertension, coadministration of aprepitant (approximately 230 mg once a day) and the moderate inhibitor diltiazem (120 mg three times a day for 5 days) resulted in a 2-fold increase in the AUC of aprepitant and a 1.7-fold increase in that of diltiazem. No clinically significant changes in ECG, heart rate, or blood pressure were observed beyond those induced by diltiazem alone.

MANAGEMENT: The manufacturer of aprepitant recommends avoiding its concomitant use with potent or moderate inhibitors of CYP450 3A4.

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.