Apixaban (Eliquis)

An oral direct factor Xa inhibitor approved for:

        1) Stroke prevention in non-valvular atrial fibrillation, using the following dosing 

  • 5 mg twice daily
  • 2.5 mg twice daily if at least two of the following characteristics:
    • Age ≥ 80 years old
    • Weight ≤ 60kg
    • Scr ≥ 1.5mg/dL
  • 2.5 mg twice daily when used concurrently with agents that are strong dual inhibitors of  CYP3A4 and p-glycoprotein
  • In patients already taking 2.5mg twice daily, avoid coadministration with strong dual inhibitors of CYP3A4 and p-glycoprotein

        2) Treatment of DVT/PE (10mg twice daily for 7 days, then 5mg twice daily)

        3) Long term prevention of DVT/PE after initial 6 months of treatment (2.5mg twice daily)

        4) Prevention of DVT/PE following hip or knee replacement (2.5mg twice daily)

NOTE:  Not recommended for patients with severe hepatic impairment.

       

Relevant Clinical Trials  

 

Stroke Prevention in Atrial Fibrillation

1) Apixaban vs. Warfarin

Granger et al. Apixaban versus warfarin in patients with atrial fibrillation. New Engl J Med 2011; 365(11):981-992. (ARISTOTLE trial)

2) Apixaban vs. Aspirin

Connolly et al. Apixaban in patients with atrial fibrillation. New Engl J Med 2011; 364(9):806-817. (AVERROES trial)

Treatment of DVT/PE

Agnelli G et al.  Oral apixaban for the treatment of acute venous thromboembolism.  New Engl J Med 2013; 369:799-808 (AMPLIFY trial)

Agnelli G et al.  Apixaban for the extended treatment of venous thromboembolism.  New Engl J Med 2013; 368:699-708 (AMLIIFY-EXT trial)

Therapeutic monitoring

Apixaban is not intended to be monitored using routine coagulation testing. Its fixed dosing is not intended to be adjusted on the basis of any coagulation laboratory parameter.

As a result of FXa inhibition, apixaban prolongs clotting tests such as prothrombin time (PT)/ INR, and activated partial thromboplastin time (aPTT). Changes observed in these clotting tests at the expected therapeutic dose, however, are small, subject to a high degree of variability, and not useful in monitoring the anticoagulation effect of apixaban.

Suggestions for Reversal and Management of Bleeding

There is now an FDA approved reversal agent for apixaban, see andexanet alfa and Guidelines For Reversal of Anticoagulants.

Mild Bleeding

  • Delay next dose or discontinue therapy

Moderate to Severe Bleeding

  • Symptomatic treatment
  • Mechanical compression
  • Surgical intervention
  • Fluid replacement and hemodynamic support
  • Blood product transfusion
  • Oral charcoal may block the continued absorption from the gut even if charcoal is given 6 hours after ingestion of apixaban.
  • NOTE: Not dialyzable

Life Threatening Bleeding

  • Measures above
  • Last resort: PCC (Kcentra) and andexanet alfa when this product becomes available.