FDA:Safety of Dabigatran Etexilate

A new perspective from the U.S. Food and Drug Administration (FDA) published in the New England Journal of Medicine(1) states that the agency has not changed its recommendations regarding Pradaxa® (dabigatran etexilate), following the November 2012 Mini-Sentinel evaluations.(2) The FDA stated that bleeding rates associated with new use of Pradaxa® do not appear to be higher than those with new use of warfarin, which is consistent with observations from the pivotal RE-LY® trial.The perspective was published online on March 13, 2013.

The Mini-Sentinel evaluated new information about the risk of serious bleeding associated with the use of blood thinners (anticoagulants): Pradaxa® and warfarin. The FDA investigated the actual rates of bleeding occurring in the stomach and intestines (gastrointestinal bleeding, GIH) and a type of bleeding in the brain (intracranial hemorrhage, ICH) for new users of Pradaxa® compared to new users of warfarin. This assessment was done using insurance claims and administrative data from the FDA’s ongoing Mini-Sentinel pilot of the Sentinel Initiative.

In the November 2012 Mini-Sentinel evaluations, the FDA stated: “For the populations in the Mini-Sentinel data assessment, the combined incidence rate (ICH and GIH events per 100,000 days at risk) was 1.8 to 2.6 times higher for new users of warfarin than for new users of Pradaxa®.” and that “Pradaxa® provides an important health benefit when used as directed.”

Dabigatran etexilate

Dabigatran etexilate was the first of a new generation of oral anticoagulants/direct thrombin inhibitors (DTIs) targeting a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.

Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of thrombin (both free and clot-bound), the central enzyme in the process responsible for clot (thrombus) formation. In contrast to vitamin-K antagonists, which variably act via different coagulation factors, dabigatran etexilate provides effective, predictable and consistent anticoagulation with a low potential for drug-drug interactions and no drug-food interactions, without the need for routine coagulation monitoring or dose adjustment.

Clinical experience of Pradaxa® exceeds that of all other novel oral anticoagulants: It equates to over 1.4 million patient-years in all licensed indications and spans over 80 countries worldwide.

One patient year equates to the treatment of a single patient over a whole year (365 days). The expression of clinical experience in patient years provides a more realistic assessment of experience with a treatment than the mere number of patients treated without relation to their individual treatment time.