Edoxaban (Savaysa)

An oral direct Xa inhibitor approved for:

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

  • 60 mg once daily (if CrCl is > 50-95 ml/min)
  • 30 mg once daily (if CrCl is 15-50 ml/min)
  • NOTE:  Contraindicated if CrCl is > 95ml/min, due to increased risk of stroke

2) Treatment of DVT/PE

  • 60 mg once daily after initial 5-10 days of parenteral anticoagulant therapy (if CrCl is > 50ml/min)
  • 30 mg once daily after initial 5-10 days of parenteral anticoagulant therapy if
  • CrCl is 15-50 ml/min
  • Patient weight is < 60kg
  • Taking certain concomitant P-gp inhibitors

Relevant Clinical Trials

Stroke Prevention in Atrial Fibrillation

Giugliano RP,et al   Edoxaban versus warfarin in patients with atrial fibrillation..  N Engl J Med. 2013; 369: 2093-104 (ENGAGE AF-TIMI 48 Trial)

Treatment of DVT/PE

Hokusai-VTE Investigators.  Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med  2013;  369:1406-15.

 

Therapeutic Monitoring

Edoxaban 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, edoxaban 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 edoxaban

Suggestions for Reversal and Management of Bleeding

There is NO REVERSAL AGENT OR ANTIDOTE for edoxaban. Very limited data, primarily non-human, are available to guide management of bleeding.

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 edoxaban.
  • NOTE: Not dialyzable

Life Threatening Bleeding

  • Measures above
  • Last resort: PCC - Kcentra