Drug Interaction Report

MONITOR: Coadministration with eliglustat may increase the plasma concentrations of drugs that are primarily metabolized by CYP450 2D6. When metoprolol, a CYP450 2D6 substrate, was administered following multiple doses of eliglustat 127 mg twice daily, mean metoprolol peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.7- and 2.3-fold, respectively, in CYP450 2D6 extensive metabolizers and 1.2- and 1.6-fold, respectively, in intermediate metabolizers compared to metoprolol administered alone.

MANAGEMENT: Caution is advised if eliglustat is used concomitantly with medications that undergo metabolism primarily by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever eliglustat is added to or withdrawn from therapy.

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.

GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.