EMA updates dabigatran label due to increased fatal bleeds

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The European Medicines Agency (EMA) has updated the safety label for Boehringer Ingelheim’s dabigatran (Pradaxa) after several cases of fatal bleeding events were reported. The number of increased bleeds may stem from the increased use of the drug as a result of approval of a new indication (preventing stroke and systemic embolism in non-valvular atrial fibrillation patients), EMA said in a statement.

“The agency is aware of recent media interest regarding fatal cases of bleeding in patients treated with Pradaxa,” EMA wrote. “The risk of bleeding with anticoagulant medicines is well-known.”

When dabigatran was first approved in August 2011, the European Union (EU) recommended that clinicians evaluate patients for signs of bleeding and discontinue if patients run the risk of severe bleeds. Currently, dabigatran is contraindicated for a number of patients: those with severe renal impairment and patients with bleeding. The drug should also be used with caution in elderly patients and those with moderate renal impairment.

In October, the agency’s Committee for Medicinal Products for Human Use (CHMP) recommended changes to dabigatran’s label after reports of fatal cases of bleeding in Japan.

The current recommendations included advice that medical professionals should assess a patient’s renal function at least once a year in patients over the age of 75. CHMP said that these recommendations will be sent in a letter to the marketing authorization holder.

Since Nov. 6, a total of 256 reports of serious bleeds that resulted in death on dabigatran were recorded in the EudraVigilance database. Of these reports, 21 events were filed in the EU.

On Nov. 9, Boehringer Ingelheim updated the prescribing information for dabigatran, which included a change in the storage and handling of the drug. Within the updates, the company recommended renal function assessment and coadministration considerations and added clarification around international normalized ratio (INR) testing with the drug, much like the updates recommended in the EU. Lastly, the company said that INR testing should be avoided due to its unreliability in patients administered dabigatran.

“The number of reports of bleedings in patients treated with Pradaxa has to be seen in the context of the rapidly increasing use of Pradaxa worldwide as a result of approval of a new indication (prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation) in several regions of the world and also the increased awareness about the drug, a factor that is known to lead to higher than usual reporting of side effects,” according to EMA.

EMA said that it will continue to monitor the risk of bleeding with the drug and its overall safety profile. “The committee will look again at all case reports received so far to confirm that the frequency of occurrence of fatal bleeds has not increased and that the recommended product information is appropriate to manage the risk.”