What is the recommended reversal agent for Eliquis (apixaban)?

Reversal Agent for Eliquis (Apixaban)

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

Mechanism of Action and Efficacy

• Andexanet alfa is a recombinant modified factor Xa protein that acts as a decoy, binding to apixaban with high affinity and reversing its anticoagulant effect 1, 3
• It rapidly reduces anti-FXa activity by >90% within minutes of administration, with this effect maintained during the 2-hour infusion period 1
• Clinical hemostasis was rated as excellent or good in 79-80% of patients with major bleeding in clinical studies 1

Indications for Use

Andexanet alfa should be used in patients taking apixaban when:

• Life-threatening bleeding occurs
• Bleeding into critical organs (especially intracranial hemorrhage)
• Persistent major bleeding despite local hemostatic measures 1, 2

Dosing Regimen

Dosing is based on the last dose of apixaban and time since last dose:

1. Low Dose Regimen (for patients on ≤5 mg apixaban or if last dose was >8 hours ago):

   • 400 mg IV bolus at approximately 30 mg/min
   • Followed by 480 mg IV infusion over 2 hours 1, 2

2. High Dose Regimen (for patients on >5 mg apixaban or if last dose was <8 hours ago):

   • 800 mg IV bolus at approximately 30 mg/min
   • Followed by 960 mg IV infusion over 2 hours 1, 2

Important Safety Considerations

• Thromboembolic events occur in 10-18% of patients within 30 days after administration 1
• FDA black box warning for thromboembolic risks, ischemic events, cardiac arrest, and sudden death 2
• Monitor for thromboembolic events and reinitiate anticoagulation when medically appropriate 2
• Anti-FXa activity may increase again after infusion is stopped (rebound anticoagulation) 1

Alternative Options

When andexanet alfa is not available, 4-factor prothrombin complex concentrate (4F-PCC) may be used:

• Dose: 25-50 units/kg based on clinical scenario 1
• However, studies show inconsistent evidence for reversal of Xa inhibitors with PCCs 4
• PCCs are not specific antidotes for factor Xa inhibitors 4

Post-Reversal Management

• Monitor for rebound anticoagulation after reversal agent administration 1
• Consider restarting anticoagulation 7-14 days after confirmed hemostasis 1
• Anticoagulant therapy should be resumed as soon as medically appropriate to prevent thrombotic events 3

Emerging Reversal Agents

Ciraparantag (PER977) is an investigational small synthetic molecule that:

• Binds to apixaban and other anticoagulants
• Has shown promise in early clinical studies
• However, its development is behind andexanet alfa 4

Andexanet alfa is currently the only FDA-approved specific reversal agent for apixaban, with demonstrated efficacy in rapidly reducing anti-FXa activity and improving hemostasis in patients with major bleeding.