Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 and/or P-glycoprotein (P-gp) may decrease the plasma concentrations of eliglustat, which is primarily metabolized by CYP450 2D6 and, to a lesser extent, CYP450 3A4. Eliglustat is also a substrate of P-gp efflux transporter. In pharmacokinetic studies, treatment with the potent CYP450 3A4/P-gp inducer rifampin (600 mg once daily) decreased eliglustat peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 90% in CYP450 2D6 extensive and intermediate metabolizers administered eliglustat 127 mg twice daily, and 95% in poor metabolizers administered eliglustat 84 mg twice daily. No data are available for use with other, less potent inducers.

MANAGEMENT: Patients receiving eliglustat with CYP450 3A4 inducers should be monitored for potentially diminished pharmacologic response to eliglustat. Concomitant use should be avoided if an interaction is suspected.

GENERALLY AVOID: Grapefruit juice may significantly increase the systemic exposure to eliglustat. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because eliglustat is predicted to cause prolongation of the PR, QTc, and QRS cardiac intervals at substantially elevated plasma concentrations, consumption of grapefruit juice during treatment may increase the risk of bradycardia, atrioventricular block, cardiac arrest, and serious ventricular arrhythmias such as torsade de pointes.

MANAGEMENT: Patients treated with eliglustat should avoid consumption of grapefruit and grapefruit juice.