direct thrombin inhibitor

Dabigatran

  • An oral direct thrombin inhibitor approved for :

             1) Stroke prevention in atrial fibrillation

             2) Treatment of DVT and PE in patients who have been treated with a parenteral anticoagulant for 5-10 days

             3) Long term prevention of recurrent DVT/PE in patients who have been previously treated for DVT/PE

 

Relevant Clinical Trials

Stroke Prevention in Atial Fibrillation

Treatment of DVT/PE

Extended Treatment of DVT/PE

Monitoring

  • Dabigatran 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. 

    In certain clinical situations in which the presence or absence of anticoagulant effect induced by dabigatran needs to be measured, the UW Medicine Dabigatran Assay can be used.

Administration Considerations

  • Do not break, chew or crush capsules
  • Keep capsules in original container – do not store or place in other containers
  • After opening original container, capsules expire in 120 days

Suggestions for Reversal and 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 (if dabigatran administered < 2 hrs prior)
  • Hemodialysis (60% removal)

Life Threatening Bleeding

  • Measures above
  • Charcoal filtration
  • Idarucizumab (Praxbind)

 

General information and Dosing

Rivaroxaban

An oral direct factor Xa inhibitor approved for:

  • Stroke prevention in atrial fibrillation (20 mg daily, or 15 mg daily in patients with CrCl 15-50 ml/min)
  • Treatment of DVT/PE (15 mg bid for 21 days, then 20 mg daily)
  • Prevention of DVT/PE following total hip or knee replacement (10 mg daily)

Relevant Clinical Trials

Atrial Fibrillation

DVT/PE Treatment

Hip Replacement

Knee Replacement

Therapeutic monitoring

Rivaroxaban 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. In certain clinical situations in which the absence of anticoagulant effect induced by rivaroxaban needs to be assured, prothrombin time (PT) and partial thromboplastin time (PTT) can be evaluated and should be normal.

These settings include:

  • To assure appropriate rivaroxaban clearance prior to invasive procedures
  • To assure appropriate rivaroxaban clearance prior to thrombolytic therapy for acute ischemic stroke

NOTE: There is no reliable correlation between elevated PT/PTT and therapeutic effect

Hillarp A et al. Effects of oral direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays. J Thromb Haemost 2011; 9:133-9.

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 (if rivaroxaban administered < 2 hrs prior)
  • NOTE: not dialyzable

Life Threatening Bleeding

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

Eerenberg ES et al. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 2011; 124: 1573-9

 

Dabigatran (Pradaxa)

  • A new oral direct thrombin inhibitor approved for stroke prevention in atrial fibrillation

Relevant Clinical Trials

UW Medicine Dabigatran Clinical Screening Checklist

Medication Guide

Patient Education Documentation

Therapeutic Monitoring

Dabigatran 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. 

In certain clinical situations in which the presence or absence of anticoagulant effect induced by dabigatran needs to be measured, the UW Medicine Dabigatran Assay can be used.

Suggestions for Reversal and Management of Bleeding

There is NO REVERSAL AGENT OR ANTIDOTE for dabigatran.  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 (if dabigatran administered < 2 hrs prior)
  • hemodialysis (60% removal)
Life Threatening Bleeding
  • measures above
  • charcoal filtration
  • last resort: PCC - Bebulin 25-50 U/kg 

Administration Considerations

  • Do not break, chew or crush capsules
  • Keep capsules in original container – do not store or place in other containers
  • After opening original container, capsules expire in 120 days