Drug Interaction Report

Based on in vitro data, coadministration with potent inhibitors of CYP450 3A4 and/or 2C19 may be expected to increase the plasma concentrations of ambrisentan, which is a substrate of these isoenzymes. However, administration with ketoconazole (potent CYP450 3A4 inhibitor) or omeprazole (potent CYP450 2C19 inhibitor) did not result in clinically relevant changes in ambrisentan exposure.

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.