Following post-market reports of severe bleeding with dabigatran (Pradaxa, Boehringer Ingelheim), the FDA is to investigate whether the reports show that severe bleeding is more frequent than would be expected given the results of the RE-LY study (Connolly et al, N Engl J Med 2009; 361:1139–51). The RE-LY study showed that in patients with atrial fibrillation, the incidence of major bleeding with 150mg Pradaxa was similar to warfarin.
However, despite its review, the FDA says it “continues to believe that Pradaxa provides an important health benefit when used as directed and recommends that healthcare professionals who prescribe Pradaxa follow the recommendations in the approved drug label.”
In a press statement from Boerhinger Ingelheim, the company said it “firmly stands behind” the efficacy and the safety of its anticoagulant. It added: “Patient safety is our top priority and we frequently communicate with the FDA and regulatory agencies around the world to ensure they have the most up-to-date information regarding the safety profile of Pradaxa.”
The European Medicine Agency, in response to reports of fatal cases of bleeding in Japan, recommended further changes to the prescribing information for the drug in October. In a statement, it said: “The recommended updated product information includes advice that renal function be assessed in all patients before starting Pradaxa treatment; while on treatment, renal function should be assessed in all patients at least once a year in patients over 75 years of age and whenever a decline in renal function is suspected in patients of any age.”
In the USA, Pradaxa is approved in two doses 75mg and 150mg. In Europe, under the recommendations of the European Medicine Agency, the drug is also approved in two doses-110mg and 150mg. The 110mg and 150mg doses were evaluated in the RE-LY study.