PRADAXA: A Bleed Without an Antidote

by Jim Orr

PRADAXA is a prescription blood-thinning drug made by Boehringer Ingelheim. It was approved by the FDA in October of 2010 to reduce the risk of stroke and blood clots in people with atrial fibrillation. Since its approval, the drug has been linked to serious and life-threatening bleeding risks.

Why Take a Blood Thinner?

Atrial fibrillation is a heart condition which causes irregular and often rapid heart rate that can result in poor blood flow to the body. During atrial fibrillation, the heart’s two upper chambers (the atria) beat chaotically and irregularly — out of coordination with the two lower chambers (the ventricles) of the heart. Atrial fibrillation symptoms include heart palpitations, shortness of breath and weakness. Additionally, people who have atrial fibrillation are at risk for strokes and heart attacks, especially if they have other medical problems. With atrial fibrillation, the chaotic rhythm may cause blood to pool in the heart and form clots. If a blood clot forms, it can dislodge from the heart and travel to the brain, causing a stroke. Strokes resulting from atrial fibrillation patients can be fatal.

Because of the risk of severe stroke in atrial fibrillation patients, they are treated with a blood thinner to reduce the risk.  For decades, this has been accomplished with aspirin in low risk patients and Warfarin (Coumadin) in higher risk patients. While reducing the risk of stroke, blood thinners unfortunately expose patients to another risk  – the risk of serious internal bleeding.

Warfarin Risks Manageable

With Warfarin (Coumadin), about 1 in every 33 patients will suffer a major bleed.[1] While the risk of such a bleed is high, the treatment for a Warfarin-induced bleed is very effective. Should a major bleed occur, oral or parenteral vitamin K1 can be given which reverses the anti coagulation effects of the Warfarin (Coumadin). This is referred to as a reversal agent, and the Full Prescribing Information (i.e., package insert) for Warfarin provides very specific instructions on how to use oral parenteral vitamin K1 to reverse a bleed.[2] Also, the package insert for Wafarin very prominently warns about the risk of bleeding associated with its use.  In fact, the very first words of the package insert in all caps and bold type are: “WARNING: BLEEDING RISK”.

Worldwide Concern Over Pradaxa

Warfarin works by inhibiting vitamin K-dependent coagulation factors. This is why giving vitamin K1 reverses Warfarin related bleeds. PRADAXA, on the other hand, produces anti coagulation through a different mechanism by directly inhibiting thrombin. Although Boehringer Ingelheim claims in their package that PRADAXA causes no greater risk of bleeds than Warfarin, the FDA issued a “Drug Safety Communication” on December 7, 2011 stating that the “FDA is evaluating post-marketing reports of serious bleeding events in patients taking Pradaxa.”  The FDA’s counterparts in Australian and Europe issued similar alerts.[3] Boehringer Ingelheim has even admitted to at least 260 confirmed fatal bleeding events in patients taking Pradaxa. Furthermore, the Institute for Safe Medication Practices has reported that in the first quarter of 2011, PRADAXA produced two different kinds of signals of major drug risk: a large volume of total serious reports, and large numbers of reports for a specific adverse event, hemorrhage.  They found that 932 serious adverse drug events have been reported where PRADAXA was the primary suspect drug.

PRADAXA Manufacturer Denies Risks

Because of the large number of significant adverse events, serious questions have emerged about Boehringer Ingelheim’s claims that PRADAXA does not involve any greater risk of bleeding.  In addition, it is undisputed that PRADAXA, unlike Warfarin (Coumadin), does not have a reversal agent that can be administered should a bleed occur.  Some treatments for a PRADAXA bleed are being evaluated (for example fresh frozen plasma and prothrombin complex concentrate), but the effectiveness and speed of these treatments are uncertain.[1]

In light of the serious risk of life-threatening bleeds associated with PRADAXA and the lack of any established effective antidote, what did the Boehringer Ingelheim initial package insert for PRADAXA tell physicians?  What did their PRADAXA marketing brochures tell physicians?  NO WARNING!  Neither of these PRADAXA communications to physicians contained a warning about the fact that their patients could experience a life threatening bleed and there may be nothing the physician can do to effectively save their lives. Although a warning about the lack of a reversal agent has since been added to the PRADAXA package insert, it does not appear until the 5th page of the package insert.  Clearly, a black box warning should be added to the package insert of PRADAXA warning about the high risk of life threatening bleeds and no reversal agent and that no effective treatment for stopping the bleed has been established.

[1] Miller, et al; Meta-Analyis of Efficacy and Safety of New Oral Anticoagulants (Dabigatran, Rivaroxaban, Apixaban) Versus Warfarin in Patients with Atrial Fibrillation; Am J. Cardiol. (2012).



[4]Kaatz, et al., Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors, Am. J. Hematol. 87:S141 (2012)

by Jim Orr

Jim Orr is a licensed attorney and a partner at HO&P focusing on business and personal injury litigation. Jim was selected multiple times to the Super Lawyers List and has tried 70+ cases to verdict.