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 increase the plasma concentrations of nilotinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Because nilotinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of nilotinib. The mechanism of interaction is unknown. Compared to the fast state, nilotinib systemic exposure (AUC) increased by 82% when the dose was given 30 minutes after a high-fat meal. Because nilotinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

MANAGEMENT: Patients treated with nilotinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. In addition, no food should be consumed for at least 2 hours before and 1 hour after a nilotinib dose.