FDA Investigating Pradaxa Bleeding Reports

U.S. health regulators have opened a safety investigation of Pradaxa (dabigatran) following reports of serious bleeding in patients treated with the blood thinner. According to a Drug Safety Communication issued yesterday, the Food & Drug Administration (FDA) is trying to determine if bleeding is occurring in Pradaxa patients more commonly than would be expected, based on the clinical trials that supported its approval.

Pradaxa, approved by the FDA in October 2010, is used to prevent strokes in people with atrial fibrillation, and is intended to replace the blood thinner, warfarin. Unlike warfarin, Pradaxa is not associated with dangerous interactions with some foods. However, excessive bleeding from warfarin can be treated with vitamin K, while there is no antidote for this side effect when it occurs in Pradaxa patients.

Since its approval, a total of approximately 1.1 million Pradaxa prescriptions were dispensed and approximately 371,000 patients received Pradaxa prescriptions, according to the FDA.

Bleeding that may lead to serious or even fatal outcomes is a well-recognized complication of all anticoagulant therapies, and the Pradaxa label does bear a warning about this potential side effect. In a large clinical trial involving 18,000 patients that compared Pradaxa and warfarin, major bleeding events occurred at similar rates with the two drugs, the FDA said.

In its Drug Safety Communication, the FDA said it is currently evaluating post-marketing reports of serious bleeding events in patients taking Pradaxa, but did not indicate how many such reports it had received. The agency also said it continues to believe Pradaxa “provides an important health benefit when used as directed,” and has told patients with atrial fibrillation not to stop taking the drug without talking to their doctor.

Last month, TheHeart.org reported that there have been 260 reports of fatal bleeding among Pradaxa patients worldwide, including 21 in Europe. The events occurred between March 2008 and October 31, 2011, according to a spokesperson from Boehringer Ingelheim, the maker of Pradaxa. The company has maintained that the number was in line with expectations for bleeding events based the drug’s clinical trials.

According to a report issued in October by the Institute for Safe Medication Practices (ISMP), since its U.S. approval last year, Pradaxa has been named in more FDA adverse event reports than over 98% of the medications the group monitors. Pradaxa side effect reports outpaced most other drugs, including warfarin, with the majority involving serious bleeding or blood clots in the elderly, the ISMP said.

That same month, the European Medicines Agency (EMA) cautioned European doctors to subject Pradaxa patients older than 75, as well as those with renal impairment, to annual kidney checks. Pradaxa is excreted through the kidneys, thus impaired kidney function could lead to abnormally high levels of the drug in circulation, leading to excessive risk of bleeding.

In August, Japanese regulators told Boehringer Ingelheim to issue a warning for the drug after 81 of the almost 64,000 mainly elderly patients taking it there suffered heavy bleeding.