What is the reversal agent for Eliquis (apixaban)?

Reversal Agent for Eliquis (Apixaban)

Andexanet alfa is the FDA-approved specific reversal agent for Eliquis (apixaban) in patients with life-threatening or uncontrolled bleeding. 1, 2, 3

Primary Reversal Strategy: Andexanet Alfa

Andexanet alfa (Andexxa) is the first-line reversal agent recommended by the American College of Cardiology for apixaban-associated major bleeding. 2

Mechanism of Action

• Andexanet alfa is a recombinant modified factor Xa protein that acts as a decoy, binding apixaban with high affinity and preventing it from inhibiting endogenous factor Xa. 2, 4
• It rapidly reduces anti-factor Xa activity by 92-94% within 2-5 minutes of administration. 2, 5
• The reversal effect is transient, with anti-factor Xa activity returning toward baseline approximately 2 hours after infusion completion. 2, 6

Dosing Regimen

For apixaban reversal, use the LOW-DOSE regimen: 2, 3

• 400 mg IV bolus over 15 minutes
• Followed by 480 mg continuous infusion over 2 hours (4 mg/min)

The lower dose is appropriate for apixaban compared to rivaroxaban because drug concentrations are lower with twice-daily dosing. 2, 6

Clinical Indications for Reversal

Administer andexanet alfa for: 2

• Life-threatening bleeding including intracranial hemorrhage, symptomatic or expanding extradural hemorrhage, or uncontrollable hemorrhage
• Bleeding in critical organs or closed spaces including intraspinal, intraocular, pericardial, pulmonary, retroperitoneal, or intramuscular with compartment syndrome
• Severe bleeding with hemodynamic instability or causing hemoglobin decrease ≥2 g/dL or requiring ≥2 units of RBCs
• Emergency surgery with high bleeding risk when apixaban cannot be cleared in time

Clinical Efficacy

• In the ANNEXA-4 study, 80% of patients achieved excellent or good hemostatic efficacy at 12 hours after andexanet administration. 2, 7
• In controlled trials with healthy volunteers, andexanet reduced anti-FXa activity by 92.3% compared to 32.7% with placebo (p < 0.0001). 3

Alternative Reversal Strategy: 4-Factor Prothrombin Complex Concentrate

When andexanet alfa is unavailable, administer 4-factor PCC (Kcentra) at 50 U/kg IV (maximum 4,000 units) as the alternative strategy. 2

Important Caveat About PCCs

• Earlier evidence from 2015 showed that 4-factor PCCs available in North America failed to show convincing evidence of reversal of factor Xa inhibitors in controlled studies. 1
• However, current guidelines from the American College of Cardiology still recommend PCCs as a second-line option when andexanet is unavailable. 2
• Do not use PT, INR, aPTT, or anti-FXa activity to monitor the effectiveness of PCCs when used for reversal. 2

Laboratory Assessment

• Anti-factor Xa activity assays are preferred for quantifying apixaban levels, with a threshold of >50 ng/mL considered clinically significant for serious bleeding. 2
• Do not delay andexanet administration in life-threatening bleeding situations to wait for laboratory results. 6

Critical Safety Considerations

Thrombotic Risk

Thrombotic events occur in approximately 10% of patients within 30 days of receiving andexanet alfa. 2, 7

• This emphasizes the need for prompt resumption of anticoagulation after bleeding control to significantly reduce thrombotic risk. 2, 6, 7
• Timing should be individualized based on bleeding severity, thrombotic risk, and achievement of bleeding control. 7

Transient Reversal Effect

• The reversal effect is not permanent—anti-factor Xa activity returns toward baseline approximately 2 hours after infusion completion. 2, 6
• This necessitates ongoing monitoring and supportive care beyond the infusion period. 6

Adjunctive Measures

• Tranexamic acid can be considered as adjunctive therapy to support hemostasis, though it does not directly reverse the anticoagulant effect. 2
• In trauma patients specifically, tranexamic acid (15 mg/kg or 1 g) is indicated independent of the reversal strategy. 6

Common Pitfalls to Avoid

• Do not use standard coagulation tests (PT, INR, aPTT) to guide reversal decisions or monitor effectiveness—these are unreliable for DOACs. 2
• Do not delay reversal in life-threatening bleeding while waiting for laboratory confirmation of apixaban levels. 6
• Do not forget to plan for anticoagulation resumption—the high thrombotic risk after reversal requires careful planning for when to restart anticoagulation. 2, 6, 7