Drug Interaction Report

GENERALLY AVOID: Coadministration with inhibitors of the hepatic influx transporters organic anion transporting polypeptides (OATP) 1B1 and/or 1B3 may increase the plasma concentrations and adverse effects of atrasentan. In clinical studies, coadministration with the OATP1B1 and 1B3 inhibitor cyclosporine increased the mean systemic exposure (AUC) and peak plasma concentration (Cmax) of atrasentan (single dose, 10 mg) by 380% and 430%, respectively. The risk of adverse effects such as edema, hepatotoxicity and anemia may be increased with this combination.

MANAGEMENT: Concomitant use of atrasentan with OATP1B1 and/or 1B3 inhibitors should generally be avoided.

GENERALLY AVOID: Coadministration with inhibitors of the hepatic influx transporters organic anion transporting polypeptides (OATP) 1B1 and/or 1B3 may increase the plasma concentrations and adverse effects of atrasentan. In clinical studies, coadministration with the OATP1B1 and 1B3 inhibitor cyclosporine increased the mean systemic exposure (AUC) and peak plasma concentration (Cmax) of atrasentan (single dose, 10 mg) by 380% and 430%, respectively. The risk of adverse effects such as edema, hepatotoxicity and anemia may be increased with this combination.

MANAGEMENT: Concomitant use of atrasentan with OATP1B1 and/or 1B3 inhibitors should generally be avoided.

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.