Non-VKA Oral Anticoagulants (NOACs): General Considerations

• Direct Thrombin Inhibitor:
  • Dabigatran
• FXa Inhibitors:
  • Rivaroxaban
  • Apixaban
  • Edoxaban
• As per the ACCP AT10, NOACs are recommended for first line treatment of patients with DVT or PE and who are not pregnant and do not have cancer (Grade 2B)
• The risk reduction for recurrent VTE with different NOACs has not been directly compared but appears to be similar based on indirect comparison
• Compared with warfarin, NOACs have a decreased risk of bleeding (in particular intracranial bleeding)
• Edoxoban and Dabigatran require an initial 5-10 days of parenteral anticoagulation, whereas Apixaban and Rivaroxaban do not

Reversal Agent

• Dabigatran:
  • Idarucizumab is a humanized monoclonal antibody antigen-binding fragment that binds to and neutralizes Dabigatran. Dosing: Idarucizumab 5g I.V. (Administered as 2 doses of 2.5 grams I.V. no more than 15 min apart).  Consider repeat x 1 if emergent bleeding and elevated coagulation parameters
    
    Note: Plasma Dabigatran concentrations can increase more than 12-24 hrs after administration of Idarucizumab, likely due to redistribution from the extravascular compartment

• Andexanet Alfa: recombinant modified human factor Xa decoy protein that is catalytically inactive but retains the ability to bind factor Xa inhibitors in the active site. It has the ability to bind both direct factor Xa inhibitors and factor Xa inhibitors that act through antithrombin (LMWH, fondaparinux).  It is currently FDA approved for reversal of rivaroxaban and apixaban.
  • The dosing regimen (low dose or high dose) is based on the specific FXa inhibitor given, the FXa inhibitor dose, and time since it was last taken. Safety and efficacy of >1 dose of andexanet alfa has not been established. 
  • Apixaban:
    • ≤ 5 mg given in < 8 hrs or higher dose given ≥ 8 hrs:  400 mg IV bolus administered at a rate of ~30 mg/minute, followed 2 minutes later by 4 mg/minute IV infusion for up to 120 minutes
    • > 5 mg given in < 8 hrs: 800 mg IV bolus administered at a rate of ~30 mg/minute, followed 2 minutes later by 8 mg/minute IV infusion for up to 120 minutes
  • Rivaroxaban:
    • ≤ 10 mg given in < 8 hrs or higher dose given ≥ 8 hrs:  400 mg IV bolus administered at a rate of ~30 mg/minute, followed 2 minutes later by 4 mg/minute IV infusion for up to 120 minutes
    • > 10 mg given in < 8 hrs: 800 mg IV bolus administered at a rate of ~30 mg/minute, followed 2 minutes later by 8 mg/minute IV infusion for up to 120 minutes
• Kcentra dosing ranges from 12.5-50 units/kg depending on urgency of situation. FEIBA may be used at a dose up to 25 units/kg in urgent life-threatening situations

Figure 5: Urgent Reversal of Non-VKA Oral Anticoagulants (NOACs) in a Bleeding Patient: Dabigatran, Rivaroxaban, Apixaban, Edoxoban

HASHTI: Hold anticoagulant, Antidote, Supportive treatment, Hemostatic management, Transfusion, Investigate source of bleeding