Drug Interaction Report

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) may increase the plasma concentrations of lusutrombopag, which is a substrate of both efflux transporter proteins. Coadministration with cyclosporine, a P-gp and BCRP dual inhibitor, increased lusutrombopag peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 20% each compared with lusutrombopag administration alone.

MANAGEMENT: Caution is advised if lusutrombopag is prescribed in combination with P-gp and/or BCRP inhibitors. Pharmacologic response to lusutrombopag should be monitored more closely following initiation, discontinuation, or change of dosage of the concomitant P-gp or BCRP inhibitor.

GENERALLY AVOID: Grapefruit and grapefruit juice may significantly increase the plasma concentrations of orally administered ranolazine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because ranolazine prolongs QT interval in a dose-dependent manner, high plasma levels of ranolazine may increase the risk of ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation, and torsade de pointes.

MANAGEMENT: Patients treated with ranolazine should avoid consumption of grapefruit juice and other grapefruit products if possible. Otherwise, the dosage of ranolazine should be limited to 500 mg twice a day.