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.

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: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.