What is the antidote for apixaban (factor Xa inhibitor) overdose or bleeding?

Apixaban Antidote for Overdose or Bleeding

Andexanet alfa is the FDA-approved specific antidote for apixaban-related life-threatening or uncontrolled bleeding, which rapidly reverses anti-FXa activity by >90% within minutes. 1, 2

Primary Reversal Options

Andexanet Alfa (First-Line)

• Indication: FDA-approved specifically for reversal of apixaban when reversal is needed due to life-threatening or uncontrolled bleeding 2
• Mechanism: Recombinant modified human factor Xa protein that binds and sequesters factor Xa inhibitors 1
• Dosing regimen:
  • Low-dose: 400 mg IV bolus followed by 480 mg IV infusion over 2 hours
  • High-dose: 800 mg IV bolus followed by 960 mg IV infusion over 2 hours 1
• Onset: Rapid (within minutes)
• Duration: Maintained during the 2-hour infusion but may diminish afterward 1
• Important warning: Associated with serious adverse events including arterial and venous thromboembolic events (10-18% within 30 days), ischemic events, cardiac arrest, and sudden deaths 1, 2

Alternative Options When Andexanet Alfa Is Unavailable

1. Four-Factor Prothrombin Complex Concentrate (4F-PCC):

   • Can be considered when andexanet alfa is unavailable 1, 3
   • Dosing based on clinical scenario, typically 25-50 units/kg 1
   • Onset of action within 10 minutes; duration of effect approximately 8 hours 1
   • Clinical hemostasis achieved in approximately 68.6% of patients with major bleeding 3

2. Activated Charcoal:

   • If administered within 2-6 hours of apixaban ingestion for overdose
   • Can reduce apixaban AUC by 50% (if given at 2 hours) or 27% (if given at 6 hours) 4

Clinical Decision Algorithm

1. Assess bleeding severity:

   • Life-threatening or critical organ bleeding (e.g., intracranial)
   • Uncontrolled bleeding despite local hemostatic measures
   • Moderate bleeding with high-risk features

2. For life-threatening bleeding:

   • First choice: Administer andexanet alfa 1, 2
     • For patients who took apixaban ≤5 mg: Use low-dose regimen
     • For patients who took apixaban >5 mg or unknown dose: Use high-dose regimen
   • If andexanet alfa unavailable: Administer 4F-PCC (25-50 units/kg) 1, 3

3. For recent overdose without significant bleeding:

   • Consider activated charcoal if within 6 hours of ingestion 4

4. Post-reversal management:

   • Monitor for thromboembolic events and initiate anticoagulation when medically appropriate 2
   • Consider restarting anticoagulation 7-14 days after confirmed hemostasis 1
   • Monitor for rebound anticoagulation after reversal agent administration 1

Important Clinical Considerations

• Thromboembolic risk: Carefully monitor for thrombotic events after andexanet alfa administration (10-18% risk within 30 days) 1, 2
• Ciraparantag: A synthetic cationic small molecule that binds to apixaban is in clinical development but not yet approved 1, 5
• Avoid ineffective treatments: Vitamin K and fresh frozen plasma are not effective for reversing apixaban 5
• Laboratory monitoring: While not routinely required for andexanet alfa administration in emergency situations, anti-FXa activity can be used to measure the anticoagulant effect of apixaban 6

Special Situations

• Urgent/emergent surgery: For patients requiring emergency surgery (<6 hours) with recent apixaban use, consider andexanet alfa or 4F-PCC before proceeding 6
• Elective procedures: For elective procedures, simply stopping apixaban 48-72 hours before surgery is typically sufficient without requiring reversal agents 7, 6