Division of Hematology & Thromboembolism

Clinical Protocols (and Reversals): Dabigatran

Dabigatran (PradaxR) – Formulary for Patients with Atrial Fibrillation as alternative to Warfarin - December 2010

Note: Prescribers are required to ensure that patients have drug coverage or are able to pay for drug on discharge prior to initiating therapy.

Guidelines for Management of Patients on Dabigatran (Pradax®)

Conversion to or from parenteral anticoagulants

For patients currently taking dabigatran, wait 12 hours (CrCl ≥30 mL/min) or 24 hours (CrCl <30 mL/min) after the last dose of dabigatran before initiating treatment with a parenteral anticoagulant

For patients currently receiving a parenteral anticoagulant, start dabigatran 0 to 2 hours before the time that the next dose of the parenteral drug was to have been administered or at the time of discontinuation of a continuously administered parenteral drug (e.g., intravenous unfractionated heparin).

Conversion to or from warfarin

When converting from dabigatran to warfarin, adjust the starting time of warfarin based on creatinine clearance as follows:

  • For CrCl >50 mL/min, start warfarin 3 days before discontinuing dabigatran.
  • For CrCl 31-50 mL/min, start warfarin 2 days before discontinuing dabigatran.
  • For CrCl 15-30 mL/min, start warfarin 1 day before discontinuing dabigatran.
  • For CrCl <15 mL/min, no recommendations can be made – consult with Thrombosis Service.

Because dabigatran can contribute to an elevated INR, the INR will better reflect warfarin’s effect after dabigatran has been stopped for at least 2 days.

When converting patients from warfarin therapy to dabigatran, discontinue warfarin and start dabigatran when the international normalized ratio (INR) is below 2.0.

Management of Bleeding

There is no antidote to dabigatran etexilate or dabigatran.

In the event of hemorrhagic complications:

  • Discontinue treatment with dabigatran
  • Initiate appropriate clinical support, e.g. surgical or local hemostasis, transfusion of red cells, volume substitution, inotropic drugs.
  • Consider administration of platelet concentrates in cases where thrombocytopenia is present or long-acting antiplatelet drugs have been used.
  • Investigate the source of bleeding.

Consult with Thrombosis Service. Dabigatran is primarily excreted in the urine; therefore, maintain adequate diuresis. Dabigatran can be dialyzed (protein binding is low), and it may take 6-8 hours to clear dabigatran this way; however, data supporting this approach are limited. The duration of dialysis may be best guided by normalization of aPTT and/or shortening of the 2 U thrombin clotting time (TCT) to ≤60 s. There is some experimental evidence to support the role of activated prothrombin complex concentrates (e.g., FEIBA), or recombinant Factor VIIa, or concentrates of coagulation factors II, IX or X. However, their usefulness in the clinical setting has had no or very limited evaluation. In addition, in experimental models with these agents, efficacy in controlling bleeding was not paralleled by improvement in aPTT or TCT. A limitied number of patients have been treated with FEIBA, including at this hospital, with apparently good effect. As a first choice in acute, major bleeding FEIBA 50 IU/kg, infused over 30-60 minutes is suggested. Physician on call for Thrombosis Service should approve the order.

Measurement of aPTT may help guide therapy to the extent that therapeutic levels of dabigatran will cause a prolongation. TCT is very sensitive and prolonged >150 s already at therapeutic levels.

Discontinuation before surgery

Renal function
(CLCR, mL/min)
Half-life (hours)a
Timing of discontinuation after last dose of dabigatran before surgery
Standard risk of bleeding
High risk of bleedingb
> 80
13 (11–22)
24 hours
2-4 days
> 50 to ≤80
15 (12–34)
24 hours
2-4 days
> 30 to ≤50
18 (13–23)
at least 2 days (48 hours)
4 days
≤ 30c
27 (22–35)
2–5 days
>5 days

 

a Data from renal impairment study in healthy volunteers (REF), geometric mean (range).

b Types of surgery associated with a high risk of bleeding (or in major surgery where complete hemostasis may be required) include but is not limited to cardiac surgery, neurosurgery, abdominal surgery or those involving a major organ. Other procedures such as spinal anesthesia may also require complete hemostatic function. Other important determinants of bleeding risk include advancing age, co-morbidities (e.g. major cardiac, respiratory or liver disease) and concomitant use of antiplatelet therapy.

c Dabigatran etexilate is contraindicated for use in these patients. CLCR = creatinine clearance.

Ref.
Stangier J, Rathgen K, Stähle H, et al. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate. Clin Pharmacokinet 2010; 49: 259–268.
Pradax® product monograph 2010

Prepared by: Dr. Sam Schulman, Medical Director of Thrombosis Service
Reviewed by: Dr. M. Crowther, Dr. J. Weitz, Dr. C. Kearon , Dr. J. Ginsberg and J. Pickering

 

 

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