Pradaxa® Injury Risks

Pradaxa® Internal Bleeding: Serious Bleeding Injuries Linked to Pradaxa®

Since its introduction in the US in October 2010, there have been numerous reports of bleeding injuries, most notably gastro-intestinal bleeds and brain hemorrhages, associated with the use of Pradaxa®. Published reports indicate that as of August 2011 – some 10 months since approval – there were 1.1 million Pradaxa® prescriptions written for the 371,000 US patients who were taking Pradaxa®.

In December, 2011, the FDA issued a Drug Safety Communication in which it announced that it would undertake a Safety Review of Pradaxa® in order to examine serious bleeding injuries – in particular hemorrhagic strokes which can lead to death and disability. In its Safety Alert, the FDA states:

"At present, the FDA is evaluating the post-marketing reports of serious bleeding in patients taking Pradaxa submitted to the Adverse Events Reporting System (AERS) database. While serious, even fatal events have been reported, the FDA is analyzing the events to determine whether the reports of bleeding in patients taking Pradaxa are occurring more commonly than would be expected, based on observations in the large clinical trial that supported the approval of Pradaxa.

Complicating this analysis, many factors can influence whether or not adverse effects are reported, particularly the length of time a drug has been marketed, whether or not the adverse effect is described in the drug label, and the amount of publicity about an event or safety concern."
    - FDA Safety Alert, December 7, 2011.

Potential Safety Signal - Serious Adverse Events Reported to the FDA

Even before the FDA issued its safety alert, at the end of March, 2011, the FDA’s Adverse Event Reporting System (AERS) included over 900 reports of serious adverse events associated with the use of Pradaxa®. These included both abdominal (gastrointestinal) hemorrhages as well as hemorrhagic strokes (bleeding in the brain). Over 60 of these hemorrhages resulted in death. There were 60 additional deaths, 25 reports involving permanent disability and over 500 cases in which the patients were hospitalized. The reports seem to signal that the apparent risk of serious bleeding injuries may be greatest for elderly patients, particularly those who are 80 years of age and older. At the time of these reports, fewer than 300,000 Pradaxa® prescriptions had been dispensed in the US.

The Advent of Praxbind® (the Pradaxa® reversal agent)

In the fall of 2015, the FDA approved Praxbind® (idarucizumab, the Pradaxa® "reversal agent" manufactured and sold by Boehringer Ingelheim.the manufacturer of Pradaxa®. According to the drug’s prescribing information, Praxbind® is to be administered "…when reversal of the anticoagulant effect of dabigatran (Pradaxa®) is needed:
      • For emergency surgery/urgent procedures
      • In life-threatening or uncontrolled bleeding."

It is striking that five (5) years elapsed between the time that Pradaxa® entered the U.S. market and a rescue agent to save patients from uncontrollable bleeding caused by Pradaxa® was made available. Why Praxbind® wasn’t developed and made available at the same time Pradaxa® entered the market remains elusive.

The availability of a rescue agent to reverse the potential life-threatening effects of Pradaxa® does not eliminate the bleeding risk posed by it. According to New England Journal of Medicine’s Journal Watch, the wholesale cost for one prescribed dose of Praxbind® is $3,500 which, according to a company official, "has been set to help ensure the likelihood that [idarucizumab] can be available at institutions where [Pradaxa® dabigatran] patients seek emergency care." [October 20, 2015]. At least one commentator suggested that Praxabind® should be available at no cost if the use of Pradaxa® carries the risk of severe, uncontrollable bleeding that can result in death.