Is there a reversal agent for Apixaban (Eliquis)?

From the Guidelines

Yes, there is a reversal agent for apixaban called andexanet alfa, which is a recombinant modified human factor Xa protein that acts as a decoy, binding to apixaban and preventing it from inhibiting natural factor Xa, thus reversing its anticoagulant effects. According to the most recent and highest quality study, andexanet alfa is administered intravenously, with dosing based on the specific factor Xa inhibitor and timing of the last dose 1. For apixaban, the typical dose is a 400-800 mg IV bolus followed by a 4-8 mg/minute infusion for up to 2 hours.

Key Points to Consider

• Andexanet alfa is primarily used in emergency situations for life-threatening or uncontrolled bleeding in patients taking apixaban 2.
• It works rapidly, with anticoagulation reversal occurring within minutes of administration.
• However, andexanet alfa is expensive, may not be available at all hospitals, and carries risks including thrombotic events.
• In less severe bleeding situations, other measures like temporarily discontinuing apixaban, supportive care, and blood product administration may be considered first.

Administration Guidelines

• The dose and time since the last DOAC intake determine whether the low- or high-dosage protocol is applied 1.
• A low dose of andexanet alfa (400 mg IV bolus followed by 4 mg/min infusion for up to 120 minutes) is administered if the last dose of apixaban was taken ≥8 hours prior, or if the last dose of apixaban ≤5 mg was taken <8 hours prior, or if the timing is unknown 2.
• A high dose of andexanet alfa (800 mg IV bolus followed by 8 mg/min infusion for up to 120 minutes) is administered if the last dose of apixaban >5 mg was taken <8 hours prior, or if the timing is unknown 2.

Clinical Considerations

• Andexanet alfa has been shown to reduce anti-FXa activity with a high rate of haemostatic efficacy and a beneficial outcome in patients suffering from an intracerebral haemorrhage 1.
• A propensity score-matched analysis showed that the adjusted 30-day mortality rates were lower for patients treated with andexanet alfa than in matched patients receiving PCC 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

Reversal Agent: An agent to reverse the anti-factor Xa activity of apixaban is available.

• Options: Prothrombin complex concentrate (PCC), activated prothrombin complex concentrate, or recombinant factor VIIa may be considered.
• Note: These options have not been evaluated in clinical studies 3

From the Research

Reversal Agents for Apixaban

• Andexanet alfa is a recombinant modified human factor Xa protein that has been developed to reverse factor Xa inhibitors, including apixaban 4, 5, 6, 7, 8.
• Studies have shown that andexanet alfa can rapidly and effectively reverse the anticoagulant effects of apixaban in healthy volunteers and patients with acute major bleeds 4, 6.
• The FDA has approved the use of andexanet alfa for the reversal of apixaban and rivaroxaban in patients with life-threatening or uncontrolled bleeding 5.
• Andexanet alfa has a rapid onset of action, with effects sustained throughout bolus and infusion administration, and medication effects subsiding 1 to 3 hours post-administration 6.

Mechanism of Action

• Andexanet alfa works by binding to and sequestering factor Xa inhibitors, allowing endogenous factor Xa to perform its normal clotting functions 4, 8.
• This results in a reduction of anti-factor Xa activity and restoration of thrombin generation 4, 6.

Safety and Efficacy

• Andexanet alfa has been shown to be effective in reversing apixaban anticoagulation, with a reduction of anti-factor Xa activity by 95% and restoration of thrombin generation in up to 96% of patients 6.
• However, andexanet alfa has a boxed warning for thrombotic events, cardiac arrest, ischemia, and sudden death, with these adverse events occurring in up to 18% of patients in clinical trials 6, 8.