What is the reversal agent for apixaban (Eliquis)?

From the Guidelines

Andexanet alfa (Andexxa) is the recommended reversal agent for apixaban (Eliquis), as it has been shown to effectively reverse its anticoagulant effects in patients with life-threatening bleeding or requiring emergency surgery. The dosing of andexanet alfa depends on the last dose of apixaban and when it was taken, with a low-dose regimen (400mg IV bolus followed by 4mg/min infusion for up to 120 minutes) used for patients who took apixaban ≤5mg within the last 8 hours, and a high-dose regimen (800mg IV bolus followed by 8mg/min infusion) used for higher doses or unknown timing 1.

Key Considerations

• Andexanet alfa works by binding to the Factor Xa inhibitor, neutralizing its anticoagulant effect 1
• The use of andexanet alfa has been associated with a high rate of haemostatic efficacy and a beneficial outcome in patients with intracerebral haemorrhage 1
• Prothrombin complex concentrate (PCC) at 25-50 units/kg can be used as an alternative when andexanet alfa is unavailable 1
• Monitoring for recurrent bleeding is essential after the use of reversal agents, as their effect is temporary 1

Dosing Regimens

• Low-dose regimen: 400mg IV bolus followed by 4mg/min infusion for up to 120 minutes, for patients who took apixaban ≤5mg within the last 8 hours 1
• High-dose regimen: 800mg IV bolus followed by 8mg/min infusion, for higher doses or unknown timing 1

Clinical Implications

• The use of andexanet alfa has been shown to reduce anti-FXa activity and improve outcomes in patients with major bleeding 1
• The choice of reversal agent should be based on the individual patient's clinical scenario and the availability of the agent 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

The reversal agent for apixaban (Eliquis) is not explicitly stated in the label, but prothrombin complex concentrate (PCC), activated prothrombin complex concentrate, or recombinant factor VIIa may be considered, although they have not been evaluated in clinical studies 2.

From the Research

Reversal Agent for Apixaban

• The reversal agent for apixaban (Eliquis) is andexanet alfa 3, 4, 5, 6.
• Andexanet alfa is a modified, catalytically inactive, recombinant human factor Xa derivative that reverses anticoagulant effect by binding and sequestering factor Xa inhibitors 5.
• Andexanet alfa has been shown to rapidly and dose-dependently reduce unbound apixaban concentration, decrease anti-factor Xa activity, and restore thrombin generation in healthy volunteers 3, 5.

Mechanism of Action

• Andexanet alfa acts as a decoy binding entity for direct oral anticoagulants (DOACs), allowing endogenous factor Xa to perform its normal clotting functions 4.
• Andexanet alfa has a rapid onset of action, with effects observed within minutes after administration 3, 5.

Clinical Use

• Andexanet alfa is approved for the reversal of apixaban and rivaroxaban when life-threatening or uncontrolled bleeding occurs 6.
• Andexanet alfa has been shown to be well-tolerated, with mild to moderate infusion reactions being the most common adverse event 5.