Drug Interaction Report

GENERALLY AVOID: Coadministration with other myelosuppressive agents may potentiate the hematologic toxicities of ropeginterferon alfa-2b. Decreased peripheral blood counts have been reported in patients receiving interferon alfa products, including ropeginterferon alfa-2b. In two open label trials consisting of 178 patients receiving ropeginterferon alfa-2b monotherapy (dosed every 2 to 4 weeks) for the treatment of polycythemia vera, 80% of whom were exposed for 12 months or longer, leukopenia occurred in 20% of patients and thrombocytopenia in 19% of patients. Leukopenia, thrombocytopenia and anemia of grade 3 or higher occurred in 2%, 2% and 1% of patients, respectively. Moreover, infections occurred in 48% of patients, while serious infections occurred in 8% of patients.

MANAGEMENT: Concomitant use of ropeginterferon alfa-2b with other myelosuppressive agents should be avoided when possible. Otherwise, close clinical and laboratory monitoring are advised. Complete blood counts should be performed at baseline, during titration, and every 3 to 6 months or more frequently as clinically indicated during the maintenance phase.

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.