Drug Interaction Report

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of atrasentan, which is primarily metabolized by CYP450 3A4. When a single dose of atrasentan 10 mg was administered with ketoconazole, a potent CYP450 3A4 inhibitor, atrasentan systemic exposure (AUC) increased by 90%. The risk of adverse effects such as edema, hepatotoxicity and anemia may be increased with this combination. The interaction has not been studied with other, less potent CYP450 3A4 inhibitors.

MANAGEMENT: Caution is advised when atrasentan is used with potent CYP450 3A4 inhibitors. Patients should be monitored for edema, anemia and signs of hepatotoxicity such as nausea, vomiting, abdominal pain, dark urine, loss of appetite, itching and/or yellowing of the skin or eyes.

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.