What medication is used to reverse anticoagulation with Eliquis (apixaban)?

Reversal of Apixaban (Eliquis) Anticoagulation

Andexanet alfa is the specific reversal agent indicated for patients treated with apixaban (Eliquis) when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. 1

Mechanism of Action and Efficacy

• Andexanet alfa is a recombinant modified human factor Xa variant that acts as a decoy, binding to factor Xa inhibitors with high affinity, thereby restoring normal hemostatic function 2
• It rapidly decreases anti-FXa activity by >90% for apixaban within minutes of administration, with effects lasting throughout the infusion period 3
• In clinical trials, andexanet reduced anti-FXa activity by 94% compared to 21% with placebo in apixaban-treated patients 4
• The medication rapidly restores thrombin generation in 100% of apixaban-treated patients within 2-5 minutes 4

Dosing and Administration

• Andexanet alfa is administered intravenously as a bolus followed by a 2-hour continuous infusion 1
• Dosing is based on the specific apixaban dose and time since last dose 1:
  • Low dose: For apixaban ≤5 mg or when last dose was ≥8 hours prior 2
  • High dose: For apixaban >5 mg or when last dose was <8 hours prior 2
• The reversal effect is transient, with anti-FXa activity returning to pre-treatment levels approximately two hours after completion of infusion 2

Clinical Indications

• Life-threatening or uncontrolled bleeding in patients taking apixaban 1
• Specifically indicated for:
  • Intracranial hemorrhage 3, 2
  • Severe gastrointestinal hemorrhage 3
  • Bleeding into a critical organ or closed space 2
  • Persistent major bleeding despite local hemostatic measures 2

Safety Considerations

• Andexanet alfa carries a black box warning for thromboembolic risks, ischemic events, cardiac arrest, and sudden deaths 1
• Thrombotic events occurred in approximately 10% of patients in clinical studies, primarily in those who had not resumed anticoagulation 3, 2
• Prompt resumption of anticoagulation after bleeding control significantly reduces thrombotic risk 2
• Monitor for thromboembolic events and reinitiate anticoagulation when medically appropriate 1

Alternative Options

• If andexanet alfa is unavailable, prothrombin complex concentrates (PCCs) can be considered as alternative hemostatic agents 2
• PCCs were used in 85.5% of patients in the "usual care" arm of the ANNEXA-I trial for intracranial hemorrhage 3
• Activated charcoal may be used for known recent ingestion of apixaban 2

Important Clinical Considerations

• Do not delay andexanet administration in life-threatening bleeding situations while waiting for laboratory testing 2
• Andexanet alfa should not be used in patients undergoing surgery where some degree of anticoagulation is required (e.g., cardiopulmonary bypass) 3
• The medication is approved under accelerated approval based on changes in anti-FXa activity; continued approval may be contingent upon studies demonstrating improvement in hemostasis 1

Efficacy in Clinical Practice

• In the ANNEXA-4 study, 80% of patients achieved excellent or good hemostatic efficacy at 12 hours after andexanet administration 3
• In the ANNEXA-I randomized trial for intracranial hemorrhage, andexanet showed superior hemostatic efficacy compared to usual care (67% vs 53.1%) 3

Remember that laboratory testing should not delay treatment in life-threatening situations, and anticoagulation should be resumed when safe to minimize thrombotic risk.