Boehringer Ingelheim confirmed Friday that Japanese regulators asked the drugmaker to warn physicians about a risk of potentially fatal bleeding associated with use of Prazaxa (dabigatran), which is sold elsewhere as Pradaxa. In a blue letter earlier this month, the Japanese Ministry of Health, Labour and Welfare, which approved the oral anti-coagulant in January, reported that 81 patients who used the drug between March 14 and August 11 experienced severe side effects, leading to five deaths.
In the letter, the ministry said that the drugmaker needs to tell Japanese doctors about the risks, and that a lower dose may have to be given to certain patient groups at risk of bleeding, such as older adults and those with renal impairment. The MHLW also told the company to make healthcare providers aware there was no drug capable of reversing Prazaxa's anti-coagulation effect.
Boehringer Ingelheim spokesman Reinhard Malin remarked that the bleeding "is not something unknown as it comes naturally with the treatment." He added that bleeding risk factors have "likely contributed to the observed outcomes" in Japan. However, Malin noted that the company is "complying with the request and further emphasising to physicians to monitor patients who are prone to bleeding and renal impairment." In addition, he indicated that the drugmaker is working to ensure that the product's label appropriately reflects "the benefits and risks…for all patients."
Pradaxa has already been approved in 75 countries for the primary prevention of blood clots in adults who have undergone elective total hip or elective total knee replacement surgery, and is also authorised in the EU  and US for the prevention of stroke in patients with atrial fibrillation (AF). On Wednesday, the National Institute for Health and Clinical Excellence issued a preliminary recommendation  requesting further information on Pradaxa for the prevention of stroke and systemic embolism in people with AF.