Drug Interaction Report

CONTRAINDICATED: Coadministration of defibrotide with anticoagulants may increase the risk of bleeding. In vitro, defibrotide increased the activity of fibrinolytic enzymes; therefore, it may enhance the pharmacologic effects of antithrombotic agents.

MANAGEMENT: Concomitant use of defibrotide with systemic anticoagulants (except for routine maintenance or reopening of central venous lines) is considered contraindicated. Anticoagulants should be discontinued prior to initiation of defibrotide. Preferably, defibrotide administration should be delayed until the effects of anticoagulant therapy have subsided. Some authorities recommend avoiding use of anticoagulants within 24 hours of defibrotide administration, or within 12 hours in the case of unfractionated heparin. Patients should be monitored for signs of bleeding during defibrotide therapy. If bleeding develops, defibrotide should be discontinued and treatment/supportive care provided until the bleeding stops.

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.