Drug Interaction Report

MONITOR: Coadministration with potent inhibitors of uridine diphosphate glucuronosyltransferase (UGT) may increase the peak plasma concentration (Cmax) and systemic exposure (AUC) of dihydroartemisinin (DHA), an active metabolite of artesunate and substrate of UGT 1A9 or 2B7. Increased exposure to artesunate may increase the risk of adverse effects such as anemia, increased liver transaminases, thrombocytopenia, hyperbilirubinemia, acute renal failure, and leukocytosis.

MANAGEMENT: Monitoring for adverse reactions is recommended if artesunate is coadministered with potent UGT inhibitors. Dosage adjustments or alternative treatments may be required based on clinical response and tolerance.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of pazopanib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Although not studied, the interaction may increase the risk of QT interval prolongation and torsade de pointes arrhythmia as well as severe and fatal hepatotoxicity associated with the use of pazopanib.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of pazopanib. The mechanism of interaction is unknown. Administration of pazopanib with a high-fat or low-fat meal results in an approximately 2-fold increase in peak plasma concentration (Cmax) and systemic exposure (AUC).

MANAGEMENT: Patients treated with pazopanib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Pazopanib should be administered at least one hour before or two hours after a meal.