dabigatran

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)

 

Suggestions for Conversion To/From Dabigatran

CONVERSION UW MEDICINE RECOMMENDATION
From warfarin to dabigatran Stop warfarin and start dabigatran when INR < lower limit of therapeutic range

From dabigatran to warfarin

 

(NOTE: dabigatran is not intended to be used as a short term "bridge" to warfarin.  These recommendations refer to transitioning patients who are taking dabigatran on a long term basis and are switching to warfarin instead)

 

 

Clcr > 50 mL/min:   start warfarin and stop dabigatran 3 days later
Clcr 31-50 mL/min: start warfarin and stop dabigatran 2 days later
Clcr 15-30 mL/min: start warfarin and stop dabigatran 1 day later
(dabigatran may alter INR results; therefore, using INR to guide when to stop dabigatran is not reliable)
From LMWH/ fondaparinux to dabigatran Stop  parenteral anticoagulant and administer dabigatran 0-2 hours before next parenteral dose would have been given
From IV heparin to dabigatran Administer first dose of dabigatran at time of discontinuation of IV heparin infusion
From dabigatran to parenteral anticoagulant Clcr > 30 mL/min:  Start parenteral anticoagulant 12 hours after the
last dose of dabigatran
Clcr < 30 mL/min:  Start parenteral anticoagulant 24 hours after  the
last dose of dabigatran
From dabigatran to apixaban, exoxaban or rivaroxaban   stop dabigatran and begin the other agent at the time that the next dose of dabigatran would have been given

 

 

Dabigatran - Dosing and Renal Function Effects

The presence of chronic kidney disease is an independent risk factor for increased bleeding events, including hemorrhagic stroke. Please carefully consider the risks and benefits of any oral anticoagulant prior to initiating therapy.

 

Stangier J et al. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study.Clin Pharmacokinetics 2010; 49:259-68

CrCl FDA Recommended Dose  Treatment of DVT/PE

FDA Recommended Dose Stroke Prevention in AF

UW Medicine Restrictions AUC Cmax T 1/2
> 80 ml/min 150mg BID after 5-10 days of parenteral anticoagulant therapy 150 mg BID UWMedicine: RESTRICTED IF CrCl < 50 ml/min - - 14 hrs
50 – 80 ml/min 1.5 x increase 1.1 x increase 17 hrs
30 – 50 ml/min 3.2 x increase 1.7 x increase 19 hrs
<  30 ml/min Not recommended CrCl 15-30 ml/min: 75mg BID*
*based on computer modeling; not studied in patients

Consider alternative therapy

RESTRICTED

6.3 x increase 2.1 x increase 28 hrs
CrCl < 15 ml/min: not recommended

Consider alternative therapy

RESTRICTED

10-20 ml/min
on HD
Not recommended Not recommended

Consider alternative therapy

RESTRICTED

    34 hrs
(~65% removed by HD)

 

 

 

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