On November 2, 2012, the FDA issued a Drug Safety Communication informing the public that the Agency has evaluated new information about the risk of serious bleeding associated with use of the anticoagulants Pradaxa and warfarin (marketed as Coumadin, Jantoven and generics). Following the approval of Pradaxa, FDA received a large number of post-marketing reports of bleeding among Pradaxa users. As a result, FDA investigated the actual rates of gastrointestinal bleeding and intracranial hemorrhage for new users of Pradaxa compared to new users of warfarin.  This assessment was done using insurance claims and administrative data from FDA’s Mini-Sentinel pilot of the Sentinel Initiative. The results of this Mini-Sentinel assessment indicate that bleeding rates associated with new use of Pradaxa do not appear to be higher than bleeding rates associated with new use of warfarin, which is consistent with observations from RE-LY trial that was used to approve Pradaxa. FDA is continuing to evaluate multiple sources of data in the ongoing safety review of this issue.


Pradaxa and warfarin are important medications used to reduce the risk of stroke and blood clots in patients with non-valvular atrial fibrillation, the most common heart rhythm abnormality, which causes the heart to beat rapidly and irregularly.  Although these drugs reduce the number of strokes in patients with non-valvular AF, they can cause bleeding, potentially leading to serious or even fatal outcomes.  The risk of bleeding is a well-recognized risk of anticoagulant drugs. 


FDA has not changed its recommendations regarding Pradaxa.  Pradaxa provides an important health benefit when used as directed.  Healthcare professionals who prescribe Pradaxa should carefully follow the dosing recommendations in the drug label, especially for patients with renal impairment to reduce the risk of bleeding. Patients with atrial fibrillation should not stop taking Pradaxa without first talking to their healthcare professional. Stopping use of anticoagulant medications such as Pradaxa can increase the risk of stroke.  Strokes can lead to permanent disability and death.


Mini-Sentinel is a pilot project of the Sentinel Initiative.  The Sentinel Initiative is sponsored by FDA to create an active surveillance system using pre-existing electronic healthcare data from multiple sources to assess the safety of approved drugs and other medical products.


As part of an ongoing safety review of Pradaxa, FDA is also conducting two planned, protocol-based observational assessments which will assess patients taking Pradaxa and evaluate bleeding events. The agency will continue to communicate to health professionals and the public any relevant information that becomes available on the risk of bleeding and Pradaxa. 

At this time, FDA recommends that Healthcare Professionals be aware of the following updated information:


  • Results from the FDA assessment of bleeding rates using data from the Mini-Sentinel project indicate that intracranial and gastrointestinal hemorrhage incidence rates for new users of Pradaxa do not appear to be higher than the rates for the same types of bleeding for new users of warfarin.  
  • Make sure your patients know the signs and symptoms of bleeding and when to seek care.
  • Pradaxa is approved to reduce the risk of stroke and systemic embolism in patients with non-valvular AF.
  • Pradaxa is eliminated by the kidneys, therefore:
    • Renal function should be assessed prior to treatment with Pradaxa to determine the appropriate dose.
    • Renal function should be reassessed during treatment with Pradaxa if clinically indicated (e.g., fluctuating renal function, diuretic use, hypovolemia), and the dose should be adjusted following the recommendations in the drug label.
  • For patients with CrCl > 30 mL/min, the recommended dose of Pradaxa is 150 mg given orally twice daily.
  • For patients with severe renal impairment, follow the recommended doses:
    • For patients with CrCl 15-30 mL/min, the recommended dose is 75 mg orally twice daily.
    • Dosing recommendations for patients with a CrCl <15 mL/min or on dialysis cannot be provided.
  • Report adverse events involving Pradaxa to the FDA MedWatch program at: www.fda.gov/medwatch


Posted on the FDA website on 2 November 2012