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.

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.