What is the recommended reversal agent for apixaban (Factor Xa inhibitor)?

Reversal Agent for Apixaban

Andexanet alfa is the recommended specific reversal agent for apixaban in cases of life-threatening or uncontrolled bleeding. 1, 2

First-Line Reversal Strategy

Andexanet alfa works by binding and sequestering factor Xa inhibitors, rapidly reducing anti-FXa activity and restoring hemostasis. The dosing regimen depends on:

• Timing of last apixaban dose
• Severity of bleeding

Dosing Protocol:

1. High-dose regimen (for last dose <7 hours or unknown timing):

   • 800 mg IV bolus over 15-30 minutes
   • Followed by 960 mg IV infusion over 2 hours 1

2. Low-dose regimen (for last dose >7 hours):

   • 400 mg IV bolus over 15-30 minutes
   • Followed by 480 mg IV infusion over 2 hours 1

Administration should be via a 0.2 or 0.22 micron in-line polyethersulfone or equivalent low protein-binding filter, with the bolus administered at approximately 30 mg/min 2.

Alternative Reversal Strategy

If andexanet alfa is unavailable, prothrombin complex concentrate (PCC) can be used:

• Four-Factor PCC: 50 U/kg IV 1
• Activated PCC (aPCC): 50 U/kg IV 1

Important Clinical Considerations

Efficacy

• Andexanet alfa rapidly reduces anti-FXa activity by >90% within minutes 1
• The reversal effect is maintained during the 2-hour infusion but may diminish afterward 1

Safety Concerns

• Thromboembolic events: 10-18% risk within 30 days after administration 1
• Other serious adverse events: Ischemic events, cardiac arrest, and sudden deaths have been reported 2
• Monitor patients closely for thromboembolic events and initiate anticoagulation when medically appropriate 2

Additional Management

• Implement local hemostatic measures
• Provide fluid resuscitation and blood product support as needed
• Consider tranexamic acid (1 g IV, repeated every 6 hours if needed)
• Maintain adequate diuresis to help eliminate apixaban 1

Post-Reversal Management

• Monitor for rebound anticoagulation after reversal agent administration
• Consider restarting anticoagulation 7-14 days after confirmed hemostasis 1
• Use restrictive RBC transfusion thresholds (hemoglobin trigger of 70 g/L for most patients; 80 g/L for those with cardiovascular disease) 1

FDA Approval Status

Andexanet alfa is FDA-approved specifically for the reversal of apixaban or rivaroxaban in patients with life-threatening or uncontrolled bleeding. This approval was granted under accelerated approval based on changes in anti-FXa activity in healthy volunteers 2.

Limitations

• Andexanet alfa has not been shown to be effective for reversal of other FXa inhibitors besides apixaban and rivaroxaban 2
• The approval is based on pharmacodynamic markers rather than clinical hemostatic outcomes 2
• The high cost and limited availability of andexanet alfa may restrict its use in some clinical settings