Summary of Clinical Use

Patients receiving direct factor Xa inhibitor drugs to reduce thrombotic events may have bleeding crises, or may need urgent surgical intervention where the presence of anti-clotting drugs would be problematic. Andexanet alfa was designed to address these issues by effectively and rapidly removing the inhibitor drugs from the blood [4]. In vitro experiments show that andexanet alfa dose-dependently reverses the inhibitory activity of tested small-molecule FXa inhibitors, and in vivo studies show that andexanet alfa is able to restore hemostasis in a rats treated with FXa inhibitors or in a mouse model of blood loss [1]. Preliminary results of a Phase 2 clinical trial (NCT01758432) indicated that andexanet alfa rapidly reversed the action of rivaroxaban in human subjects. In May 2018, the FDA approved andexanet alfa (Andexxa®) to reverse the anticoagulation effects of rivaroxaban and apixaban, in patients that are experiencing life-threatening or uncontrolled bleeding [3].

Mechanism Of Action and Pharmacodynamic Effects

Andexanet alfa acts as a decoy and binds to FXa inhibitors. It binds FXa inhibitor drugs more strongly than it does FXa itself [1]. In this way the recombinant peptide neutralizes the inhibitor drugs in the bloodstream and restores hemostasis.