The European Medicines Agency has provided an update on the safety of Pradaxa (dabigatran etexilate) following recent media interest about fatal cases of bleeding in patients treated with the drug. On 6 November 2011 a worldwide total of 256 spontaneous case reports of serious bleeding resulting in death were recorded in the EudraVigilance database in association with the use of dabigatran, of which 21 cases were reported in the EU.
The Agency notes that the approved EU product information does recommend that doctors check for signs of bleeding and discontinue treatment in patients with severe bleeding. Furthermore, the drug is contraindicated in a number of conditions, including in patients who are bleeding and patients with severe renal impairment, and it should be used with caution and at lower doses in elderly patients and patients with moderate renal impairment (depending on indication and circumstances).
In October 2011 the Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended further changes to the product information following reports in Japan of fatal cases of bleeding and assessment of the latest available worldwide data on the risk of fatal bleeding. The product information was updated to include advice that renal function be assessed in all patients before starting treatment; while on treatment, it should be assessed 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.
The Committee states that the number of reports of bleeding in patients treated with dabigatran has to be seen in the context of its rapidly increasing use 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. Therefore it is of the opinion that the recommended changes to the use of the drug adequately manage the risk of bleeding, though it will continue to closely monitor this issue and the overall safety profile, The Committee will re-examine all case reports received so far to confirm that the frequency of occurrence of fatal bleeding has not increased and that the recommended product information is appropriate to manage the risk.