Drug Interaction Report

MONITOR: Coadministration with fidaxomicin may increase the plasma concentrations of some orally administered drugs that are substrates of the P-glycoprotein (P-gp) transporter. In vitro, fidaxomicin and its main metabolite are substrates and inhibitors of P-gp, an efflux transporter expressed in the gastrointestinal tract. When digoxin, a P-gp substrate, was coadministered with fidaxomicin (200 mg twice daily) in healthy volunteers, digoxin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 14% and 12%, respectively. Although the effect of fidaxomicin on digoxin exposure is not considered clinically relevant, a larger effect on P-gp substrates with lower bioavailability that may be more sensitive to intestinal P-gp inhibition, such as dabigatran etexilate, cannot be excluded.

MANAGEMENT: Caution is advised when fidaxomicin is used in combination with P-gp substrates that may be sensitive to intestinal P-gp inhibition.

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.