Drug Interaction Report

Coadministration with inhibitors of the isoenzyme CYP450 3A4 may increase the plasma concentrations and effects of maribavir, a CYP450 3A4 substrate. When a single 400 mg dose of maribavir was administered with a single 400 mg dose of ketoconazole, a potent CYP450 3A4 and P-glycoprotein (P-gp) inhibitor, mean maribavir peak plasma concentration (Cmax) and total systemic exposure (AUC) increased by 10% and 53%, respectively, in 19 study subjects. These changes are not considered clinically significant. No dosage adjustments are necessary when maribavir is prescribed with CYP450 3A4 inhibitors, but it may be advisable to monitor patients for maribavir-related adverse effects such as taste disturbances, nausea, diarrhea, vomiting, and fatigue.

Coadministration with inhibitors of the isoenzyme CYP450 3A4 may increase the plasma concentrations and effects of maribavir, a CYP450 3A4 substrate. When a single 400 mg dose of maribavir was administered with a single 400 mg dose of ketoconazole, a potent CYP450 3A4 and P-glycoprotein (P-gp) inhibitor, mean maribavir peak plasma concentration (Cmax) and total systemic exposure (AUC) increased by 10% and 53%, respectively, in 19 study subjects. These changes are not considered clinically significant. No dosage adjustments are necessary when maribavir is prescribed with CYP450 3A4 inhibitors, but it may be advisable to monitor patients for maribavir-related adverse effects such as taste disturbances, nausea, diarrhea, vomiting, and fatigue.

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.