Safety Update Issued for Pradaxa Related to Prosthetic Heart Valves

December 19, 2012— Boehringer Ingelheim Pharmaceuticals, Inc. (Ridgefield, CT) announced that the United States prescribing information for the company's Pradaxa (dabigatran etexilate mesylate) anticoagulant capsules was updated to include a contraindication related to its use in patients with mechanical prosthetic heart valves.

According to the company, the decision to add the contraindication was made after an interim analysis of results from the phase 2 RE-ALIGN study in patients with mechanical prosthetic heart valves—a patient population who is not currently included in the labeled indication for Pradaxa. The interim analysis showed an increased incidence of thromboembolic and bleeding events in this specific patient population when treated with dabigatran etexilate compared to warfarin.

The company advised that the RE-ALIGN study did not enroll any patients in the United States.

In the company's press release, Sabine Luik, MD, the company's Senior Vice President for Medicine & Regulatory Affairs and United States Regional Medical Director, commented, “Patient safety is our top priority, and the company took appropriate action to stop the trial and inform regulatory authorities. These findings do not affect the positive benefit-risk profile of Pradaxa 150 mg twice daily when used as indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.”

The United States Food and Drug Administration also issued a related Pradaxa Drug Safety Communication that is available on the agency's website.

The company's announcement is available online, and more information about the updated safety information is available on the company's Pradaxa website.

As stated in the press release, the safety and efficacy of Pradaxa in patients with bileaflet mechanical prosthetic heart valves (recently implanted or implanted more than 3 months before enrollment) were evaluated in the phase 2 RE-ALIGN trial. RE-ALIGN was terminated early because of significantly more thromboembolic events (valve thrombosis, stroke, transient ischemic attack, and myocardial infarction) and an excess of major bleeding (predominantly postoperative pericardial effusions requiring intervention for hemodynamic compromise) for Pradaxa versus warfarin. Therefore, the use of Pradaxa is contraindicated in patients with mechanical prosthetic valves.

The use of Pradaxa for the prophylaxis of thromboembolic events in patients with atrial fibrillation and other forms of valvular heart disease, including bioprosthetic heart valve replacement, has not been studied and is not recommended.

Pradaxa is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. The efficacy and safety of Pradaxa capsules were established in the RE-LY trial. RE-LY was a global, phase 3, randomized trial of 18,113 patients enrolled in 951 centers in 44 countries and was one of the largest stroke prevention clinical studies ever conducted in patients with nonvalvular atrial fibrillation. Pradaxa 150 mg twice daily compared to warfarin demonstrated a superior reduction in ischemic and hemorrhagic stroke. Pradaxa compared to warfarin in RE-LY showed a 36% improvement in reducing the risk of stroke in patients with nonvalvular atrial fibrillation and a 59% lower rate of intracranial bleeding, noted Boehringer Ingelheim Pharmaceuticals.