Dabigatran is one of the first direct oral anticoagulants that has been approved for sales in the Canadian market for several years now.  It was initially met with very high hope to replace warfarin therapy, to end the era for tedious INR monitoring and to eradicate the inconvenience of dietary restriction and  endless drug interactions.  After all in their landmark trial of RE-LY, it did demonstrate some evidence of superiority to warfarin for stroke prophylaxis in the setting of atrial fibrillation, in the high dose group of 150mg po BID. There was an increased risk of bleed but we didn’t really pay much attention to it at the time.  

It was a great sales pitch. In fact, many family physicians started switching their warfarin patients to dabigatran – but quickly, we saw many bleeding incidents, mostly related to gastrointestinal bleeds and it occurred not only in the usual high risk bleeders but others who were previously stable on warfarin and had no other risk factors for bleeding.  Some argued it might be due to the fluctuating renal function that was not closely monitored ; others felt the increased gastrointestinal bleed was due to the tartaric acid ingredient in the dabigatran capsule.  In the most recent BEERS criteria, dabigatran is listed as a medication to avoid due to its increased risk of gastrointestinal bleeds.

When other direct oral anticoagulants such as rivaroxaban and apixaban have become available in later years, clinicians are much more cautious in converting their patients from warfarin. They are particularly more careful by ensuring the patients’ do not have significant renal impairment.  The experience seems to be much more pleasant, at least in my opinion.

So when it comes to patients with a history of atrial fibrillation and warfarin may not be the best anticoagulation therapy, dabigatran is rarely on the top of the list for consideration anymore. However, it just scored some major points recently as idarucizumab is now available in Canada, a reversal agent for dabigatran.  All other direct oral anticoagulants don’t have a reversal agent currently, at least not one that is commercially available.

So would it change the the current practice or current view on dabigatran?  Here’s a quick summary on Idarucizumab:

Pharmacology:

  • Idarucizumab is a monoclonal antibody fragment that binds dabigatran and neutralizes its activity.

Indication:

  • It is indicated in patients treated with dabigatran where rapid reversal of its anticoagulant effect is needed, specifically in life-threatening or uncontrolled bleeding as well as for emergency surgery or urgent procedure.

Dosage & Administration:

  • The recommended dose is 5.0 gram given in two separate doses of 2.5 gram. It can be given as an infusion, diluted in at least 50mL of 0.9% NaCL or in two direct bolus injections.
  • Complete reversal is expected within minutes.

Storage & Handling

  • Idaricizumab needs to be kept refrigerated (2-8 degree celsius) if not used. However prior to use, it may be kept at room temperature (25 degree celsius) for up to 48 hours if vials were kept in the original package. If exposed to light, it may be good up to 6 hours only.

I am glad that we finally have a reversal agent for dabigatran. If a patient develops a serious bleeding risk or requires urgent surgery or procedure that requires reversal of the anticoagulant effect, then we have the option to reverse the effect immediately.

However, it does not change or increase its approval rate as a direct oral anticoagulant for atrial fibrillation. The fact that idaricizumab needs to be given as an infusion or a direct bolus injection, suggests that it probably needs to be administered in a hospital setting, with more investigations readily available for monitoring and for safe use.

So when a patient develops serious bleeds in the community, it does not make things easier.  It probably is still safer to treat with rivaroxaban or apixaban as they tend to be associated with less risk for bleed. This is what my experience so far. I still will not recommend dabigatran, despite the availability of a specific reversal agent.

Advertisements