Drug Interaction Report

GENERALLY AVOID: Andexanet alfa may interfere with the anticoagulant effects of heparin. Andexanet alfa is a molecularly modified factor Xa decoy protein able to competitively bind factor Xa inhibitors without exhibiting any anticoagulant effects. In vitro studies suggest that andexanet alfa is able to bind unfractionated heparin (UFH) as well as the heparin-antithrombin complex. One case report illustrates this interaction in a 70 yr old male on rivaroxaban (20 mg daily) who received low dose andexanet alfa (400 mg intravenous bolus followed by 4 mg/min infusion) at the beginning of an endovascular aortic repair. About 40 minutes after he started andexanet alfa, intraoperative heparinization was initiated; however, despite receiving an 8000 unit UFH bolus and then another 6000 units of UFH over the next hour, the patient's activated clotting time (ACT) never exceeded 152 seconds (goal > 250 seconds). In clinical studies, anti-factor Xa activity returned to placebo levels 4 hours after the start of andexanet alfa therapy (i.e., 2 hours after the completion of a 2-hour infusion). Unfortunately, since heparin was given within 4 hours of the start of andexanet alfa in this patient, it is unclear whether separation of heparin and andexanet alfa by more time may mitigate the interaction.

MANAGEMENT: Andexanet alfa is not recommended for use as an antidote for heparin nor should it be used to reverse direct factor Xa inhibitors (apixaban or rivaroxaban) prior to a situation in which heparinization is needed (e.g., certain surgeries). If andexanet alfa has already been given and the patient requires anticoagulation for a procedure, an alternative anticoagulant should be considered (e.g., direct thrombin inhibitor).