Is there a reversal agent for Apixaban (apixaban)?

From the Guidelines

Yes, there is a reversal agent for apixaban called andexanet alfa (brand name Andexxa), which is specifically designed to reverse the anticoagulant effects of factor Xa inhibitors like apixaban in emergency situations such as life-threatening or uncontrolled bleeding. Andexanet alfa works by acting as a decoy protein that binds to apixaban, preventing it from inhibiting factor Xa and thereby restoring normal blood clotting 1. The dosing depends on the specific factor Xa inhibitor and when it was last taken, with higher doses needed for patients on higher doses of apixaban or who took it recently. For apixaban, a low-dose regimen consists of a 400 mg IV bolus followed by a 4 mg/minute infusion for up to 120 minutes, while a high-dose regimen uses an 800 mg bolus followed by an 8 mg/minute infusion 1.

Key Points

• Andexanet alfa is a modified human recombinant factor Xa decoy protein that lacks catalytic activity and is a specific urgent reversal agent for rivaroxaban and apixaban 1.
• The ANNEXA-4 study demonstrated that andexanet alfa can effectively reverse the anticoagulant effects of apixaban, with a reduction in anti-FXa activity of 92% from baseline in apixaban-treated patients 1.
• Andexanet alfa is expensive and generally reserved for severe bleeding situations, not routine reversal.
• Other strategies for managing apixaban-associated bleeding include activated charcoal (if recently ingested), prothrombin complex concentrates, and supportive measures like local hemostasis, fluid resuscitation, and blood product administration.

Clinical Considerations

• The decision to reverse the effect of an antiplatelet or antithrombotic drug in a patient with major bleeding and the choice of agent to reverse needs to be individualized, taking into account the balance between thrombosis risk and potential complications of bleeding 1.
• The interruption and the duration of interruption should be tailored to the severity of the bleeding and the likelihood of controlling the bleeding 1.

From the FDA Drug Label

An agent to reverse the anti-factor Xa activity of apixaban is available The pharmacodynamic effect of apixaban tablets can be expected to persist for at least 24 hours after the last dose, i.e., for about two drug half-lives. Prothrombin complex concentrate (PCC), activated prothrombin complex concentrate or recombinant factor VIIa may be considered, but have not been evaluated in clinical studies [see Clinical Pharmacology (12. 2)].

Reversal Agent for Apixaban:

• An agent to reverse the anti-factor Xa activity of apixaban is available.
• Options that may be considered for reversal include:
  • Prothrombin complex concentrate (PCC)
  • Activated prothrombin complex concentrate
  • Recombinant factor VIIa However, these have not been evaluated in clinical studies 2.

From the Research

Reversal Agents for Apixaban

• Andexanet alfa is a specially designed recombinant version of human factor Xa that acts as a decoy receptor to reverse the effects of factor Xa inhibitors, including apixaban 3, 4, 5.
• Andexanet alfa has been shown to reverse the anticoagulant activity of apixaban in clinical trials and is expected to be launched in the market in the near future 4.
• Prothrombin complex concentrate (PCC), activated PCC (aPCC), and recombinant factor VIIa (rFVIIa) have also been suggested as potential reversal agents for apixaban, with aPCC showing the most effective reversal effect in an in vitro study 6.
• Other specific antidotes, such as aripazine (PER-977, ciraparantag), are also being developed to reverse the anticoagulant action of apixaban and other factor Xa inhibitors 5.

Clinical Implications

• The availability of reversal agents for apixaban may increase its prescription and use in clinical situations previously felt to pose too great a risk of bleeding 7.
• Reversal agents may also be used beyond currently approved indications, such as in patients undergoing cardiac surgery with extracorporeal circulation 5.
• The development of specific antidotes for apixaban and other direct oral anticoagulants may provide an alternative for management of life-threatening bleeding events occurring with these anticoagulants 5, 7.