Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 that can also inhibit P-glycoprotein (P-gp) may significantly increase the plasma concentrations of futibatinib. Futibatinib is a substrate of both the CYP450 3A4 isoenzyme and P-gp efflux transporter. Drug interaction studies have shown that single dose administration of futibatinib with multiple doses of itraconazole, a combined potent P-gp and CYP450 3A4 inhibitor, increased futibatinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 51% and 41%, respectively, compared to futibatinib alone. Increased exposure to futibatinib may increase the risk and severity of adverse effects such as retinal pigment epithelial detachment, dry eye/corneal keratitis, pyrexia, hyperphosphatemia and soft tissue mineralization, palmar-plantar erythrodysesthesia syndrome, fatigue, nail toxicity, urinary tract infection, constipation, diarrhea, dry mouth, increased liver function tests (ALT and AST), stomatitis, abdominal pain, ascites, bile duct obstruction, and musculoskeletal pain.

MANAGEMENT: Concomitant use of futibatinib with dual P-gp and potent inhibitors of CYP450 3A4 should generally be avoided.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of futibatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to futibatinib may increase the risk of adverse effects such as retinal pigment epithelial detachment, dry eye/corneal keratitis, pyrexia, hyperphosphatemia and soft tissue mineralization, palmar-plantar erythrodysesthesia syndrome, fatigue, nail toxicity, urinary tract infection, constipation, diarrhea, dry mouth, increased liver function tests (ALT and AST), stomatitis, abdominal pain, ascites, bile duct obstruction, and musculoskeletal pain.

MANAGEMENT: Patients should be advised to avoid consumption of grapefruit or grapefruit juice during treatment with futibatinib.