How do you reverse Eliquis (apixaban)?

Reversing Eliquis (Apixaban)

For patients with life-threatening bleeding on apixaban, andexanet alfa is the specific reversal agent of choice and should be administered as an 800 mg IV bolus followed by a 960 mg IV infusion over 2 hours for recent or unknown timing of last dose. 1, 2

First-Line Reversal Options

Andexanet Alfa (Specific Reversal Agent)

• Mechanism: Recombinant modified human factor Xa protein that binds and sequesters factor Xa inhibitors 1, 3
• Dosing regimen:
  • Low dose: 400 mg IV bolus over 15-30 min, followed by 480 mg IV infusion over 2 hours
    • For last dose >7 hours before reversal
  • High dose: 800 mg IV bolus over 15-30 min, followed by 960 mg IV infusion over 2 hours
    • For last dose <7 hours before reversal or unknown timing 2
• Onset: Within 2 minutes 1
• Duration: Effect maintained during 2-hour infusion but may diminish afterward 1
• Caution: Associated with 10-18% risk of thromboembolic events within 30 days 1

Alternative Reversal Options

Prothrombin Complex Concentrate (PCC)

• When to use: When andexanet alfa is unavailable 2
• Dosing: 50 U/kg IV (with additional 25 U/kg if clinically needed) 2
• Efficacy: Studies show 65-68% effectiveness for major bleeding associated with factor Xa inhibitors 4
• Onset: Within 10 minutes 1

Activated Prothrombin Complex Concentrate (aPCC)

• Dosing: 50 U/kg IV (maximum 200 U/kg/day) 2
• Consideration: Can be considered before PCC if available 2
• Efficacy: Clinical hemostasis achieved in approximately 69% of patients with major bleeding 5

Decision Algorithm for Reversal

1. Assess bleeding severity:

   • Life-threatening bleeding (intracranial, retroperitoneal, pericardial)
   • Critical organ bleeding
   • Major bleeding with hemodynamic instability
   • Persistent bleeding despite local measures

2. Determine time of last apixaban dose:

   • <7 hours or unknown: Use high-dose andexanet alfa

   • 7 hours: Consider low-dose andexanet alfa 2

3. Check apixaban plasma levels if available:

   • 50 ng/mL with serious bleeding: Reversal recommended

   • 30 ng/mL requiring urgent high-bleeding-risk procedure: Reversal recommended 2

4. Select reversal agent:

   • First choice: Andexanet alfa
   • If unavailable: PCC 50 U/kg or aPCC 50 U/kg 2

Adjunctive Measures

• Local hemostatic measures (direct pressure, surgical intervention)
• Fluid resuscitation and blood product support as needed
• Consider tranexamic acid (1 g IV, repeated every 6 hours if needed) 2
• Maintain adequate diuresis to help eliminate apixaban 2

Post-Reversal Management

• Monitor for rebound anticoagulation
• Assess for thromboembolic complications
• Consider restarting anticoagulation 7-14 days after confirmed hemostasis 1
• Laboratory monitoring of anti-FXa activity is not reliable after andexanet alfa administration 3

Important Caveats

• Apixaban's half-life is 6-15 hours with normal renal function but extends to 17 hours with severe renal impairment 2
• Hemodialysis does not effectively remove apixaban from circulation 6
• Activated charcoal may be useful if apixaban was ingested within 2-4 hours 6
• Vitamin K and fresh frozen plasma are ineffective for apixaban reversal 7
• Patients remain at risk for delayed intracranial hemorrhage (approximately 0.95%), increasing to 4-4.5% if also on antiplatelet therapy 1

The availability of specific reversal agents has fundamentally changed the management of bleeding associated with DOACs. While supportive care remains important, prompt administration of andexanet alfa for life-threatening bleeding on apixaban can rapidly reverse anticoagulant effects and potentially improve outcomes.