Drug Interaction Report

MONITOR: Coadministration with treosulfan may increase the plasma concentrations of drugs that are substrates of CYP450 3A4, 2C19, and/or the efflux transporter P-glycoprotein (P-gp). The proposed mechanism is decreased clearance due to inhibition of these routes of elimination due to treosulfan. According to physiologically-based pharmacokinetic modeling, treosulfan is predicted to be a weak to moderate CYP450 3A4 inhibitor and weak inhibitor of CYP450 2C19, with negligible inhibitory effects on P-gp. However, according to the manufacturer, in vitro studies were unable to exclude potential drug-drug interactions with high plasma concentrations of treosulfan and CYP450 3A4, 2C19, and/or P-gp substrates.

MANAGEMENT: Caution is recommended if treosulfan is coadministered with substrates of CYP450 3A4, 2C19, and/or P-gp, particularly those with a narrow therapeutic range. Some authorities advise that if concomitant use is required, the dosage of these substrates should be administered either 2 hours before or 8 hours after administration of the treosulfan infusion. The prescribing information of the substrates may be consulted for potential dose reductions.

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.