What is idarucizumab, and why was it developed?

Idarucizumab is a specific reversal agent for dabigatran.1 It is the first specific ‘antidote’ for a non-vitamin K antagonist oral anticoagulant (NOAC) to be approved in Australia.

Idarucizumab was developed because, like warfarin and the other NOACs,2-5 dabigatran can increase the risk of bleeding and can cause significant and sometimes fatal bleeding.6

People who are anticoagulated with dabigatran who undergo surgery or invasive procedures are also at increased risk of bleeding.6

Protocols to reverse warfarin’s anticoagulant effects are well established. Vitamin K can reverse warfarin’s anticoagulant effects, and prothrombin complex concentrates (a type of pro-haemostatic agent) can correct low levels of factors II, VII, IX and X induced by warfarin.7

However, vitamin K is not expected to reverse NOAC-associated anticoagulation, and there are currently limited clinical data to support the routine use of pro-haemostatic agents for NOAC reversal.4-6,8,9

Pro-haemostatic agents may also increase the risk of thromboembolic complications when used for NOAC reversal.5,6,8,9

Although clinical data to support the use of idarucizumab are still limited, efficacy and safety in patients requiring urgent dabigatran reversal have been investigated in the open-label, phase III RE-VERSal Effects of idarucizumab on Active Dabigatran (RE-VERSE AD) study.10,11

Other NOAC reversal agents are under development but are not yet approved for use and require further clinical evaluation.8,12

When is idarucizumab prescribed, and when is it not?

Idarucizumab is only used when the rapid reversal of the anticoagulant effect of dabigatran is required for emergency situations.1

When there is life-threatening bleeding

In general, bleeding management will begin with establishing which NOAC was taken and when, initiating standard resuscitation procedures, taking blood for anticoagulant testing and stopping NOAC treatment.8,9

The next steps will depend on the severity of the bleed. Local haemostatic measures are used for mild bleeding.8

Idarucizumab can also be considered when there is clinically significant or life-threatening bleeding. Activated charcoal, hydration, transfusion support and/or pro-haemostatic agents can also be considered.8

Bleeding should be managed on a case-by-case basis, and in consultation with a haematologist.8

When an urgent surgery or procedure is needed

Idarucizumab can be considered when an urgent surgery or procedure is required, when there is insufficient time to allow for dabigatran clearance.6

In contrast, for planned surgical or invasive procedures in people taking any of the NOACs, bleeding risk is managed by treatment interruption rather than reversal.6,8,9

In such cases, timing of NOAC cessation will depend on level of renal function, estimated NOAC half-life and level of bleeding risk associated with a particular surgery.8,9

The decision to withdraw or reverse a NOAC should also be weighed against the risk of exposing a person to thrombotic events due to their underlying condition.1,4-6

There are no contraindications to idarucizumab use, although there are precautions. Refer to the idarucizumab Product Information for complete prescribing information.1

References

  1. Boehringer Ingelheim Pty Limited. Idarucizumab (Praxbind) Product Information 2016 (accessed 17 October 2016).
  2. Aspen Pharma Pty Ltd. Warfarin (Coumadin) Product Information 2016 (accessed 29 November 2016).
  3. Aspen Pharma Pty Ltd. Warfarin (Marevan) Product Information 2016 (accessed 29 November 2016).
  4. Bayer Australia Ltd. Rivaroxaban (Xarelto) Product Information 2016 (accessed 29 November 2016).
  5. Bristol-Myers Squibb Australia Pty Ltd. Apixaban (Eliquis) Product Information 2016 (accessed 29 November 2016).
  6. Boehringer Ingelheim Pty Limited. Dabigatran etexilate (Pradaxa) Product Information 2016 (accessed 28 November 2016).
  7. Tran HA, Chunilal SD, Harper PL, et al. An update of consensus guidelines for warfarin reversal. Med J Aust 2013;198:198-9.
  8. Clinical Excellence Commission. Non-vitamin K antagonist oral anticoagulant (NOAC) guidelines. Sydney, Australia, 2016 (accessed 28 November 2016).
  9. Tran H, Joseph J, Young L, et al. New oral anticoagulants: a practical guide on prescription, laboratory testing and peri-procedural/bleeding management. Australasian Society of Thrombosis and Haemostasis. Intern Med J 2014;44:525-36.
  10. Pollack CV, Jr. Evidence supporting idarucizumab for the reversal of dabigatran. Am J Med 2016;129:S73-S9.
  11. Pollack CV, Reilly PA, van Ryn J, et al. Idarucizumab for dabigatran reversal: Updated results of the RE-VERSE AD Study. American Heart Association Scientific Sessions. New Orleans, Louisiana: 2016 (accessed 15 November 2016).
  12. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS: The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC). Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Endorsed by the European Stroke Organisation (ESO). Eur Heart J 2016;37:2893-2962.