Drug Interaction Report

MONITOR: Sugammadex may potentiate the effects of anticoagulants. The mechanism of interaction has not been described. In healthy volunteers, sugammadex doses up to 16 mg/kg were associated with increases in activated partial thromboplastin time (aPTT) and prothrombin time (PT)/international normalized ratio (INR) of up to 25% for up to one hour. In a clinical trial of patients undergoing major orthopedic surgery of the lower extremity who received heparin or low molecular weight heparin (LMWH) for thromboprophylaxis, increases in aPTT and PT/INR of 5.5% and 3.0%, respectively, were observed in the hour following administration of a 4 mg/kg sugammadex dose. The changes in coagulation parameters were not associated with an increased incidence of blood loss or anemia; however, a higher dosage of sugammadex may produce clinically significant effects. In vitro, additional aPTT and PT/INR prolongations of up to approximately 25% and 50% were demonstrated when sugammadex was combined with vitamin K antagonists, unfractionated heparin, low molecular weight heparinoids, rivaroxaban, and dabigatran at peak levels of sugammadex corresponding to 4 mg/kg and 16 mg/kg doses, respectively.

MANAGEMENT: Hemostasis and coagulation parameters should be closely monitored when sugammadex is administered to patients receiving therapeutic anticoagulation for a preexisting or comorbid condition; patients who have received thromboprophylaxis drugs other than heparin and LMWH; or patients who have received thromboprophylaxis with heparin or LMWH and subsequently administered 16 mg/kg of sugammadex.

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.