Drug Interaction Report

MONITOR: Coadministration of sunitinib with elbasvir-grazoprevir may increase the plasma concentrations and the risk of adverse effects of sunitinib. The proposed mechanism by which elbasvir-grazoprevir increases sunitinib exposure has not been clearly delineated, but may involve inhibition of intestinal breast cancer resistance protein (BCRP).

MANAGEMENT: Although the interaction has not been studied, caution is advised if sunitinib and elbasvir-grazoprevir are used in combination. Dose adjustment of sunitinib as well as clinical and laboratory monitoring of sunitinib should be considered whenever elbasvir-grazoprevir is added to or withdrawn from therapy. During concomitant treatment, patients should be monitored for signs and symptoms of sunitinib toxicity such as diarrhea, hypertension, and/or neutropenia.

GENERALLY AVOID: Consumption of grapefruit or grapefruit juice during sunitinib therapy may increase the plasma concentrations of sunitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid the consumption of large amounts of grapefruit or grapefruit juice during sunitinib therapy.

Food does not appear to have clinically significant effects on the pharmacokinetics of elbasvir and grazoprevir. When a single 50 mg-100 mg dose of elbasvir-grazoprevir was administered to healthy study subjects with a high-fat meal (900 kcal; 500 kcal from fat), elbasvir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 15% and 11%, respectively, while grazoprevir Cmax and AUC increased by 2.8- and 1.5-fold, respectively, compared to administration under fasting conditions. According to the product labeling, elbasvir-grazoprevir may be administered with or without food.