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.

ADJUST DOSING INTERVAL: Food reduces the oral bioavailability of betrixaban. When administered with a low-fat (900 calories; 20% fat) or high-fat (900 calories; 60% fat) meal, betrixaban peak plasma concentration (Cmax) and systemic exposure (AUC) decreased relative to administration in the fasting state by an average of 70% and 61%, respectively, with the low-fat meal and 50% and 48%, respectively, with the high-fat meal. The effect of food on betrixaban pharmacokinetics could be observed for up to 6 hours after meal intake.

MANAGEMENT: The manufacturer recommends taking betrixaban at the same time each day with food.