Pradaxa Linked to Most Adverse Events Of Any Drug in 2012: Report

The controversial anticoagulant Pradaxa continued to lead all other drugs in adverse event reports submitted to the FDA last year, including reports of hemorrhages and deaths highlighted in a new drug safety report.  

According to an analysis (PDF) conducted by the Institute for Safe Medication Practices (ISMP), the FDA Adverse Event Reporting System (FAERS) received at least 3,292 reports during the entire year 2012 involving problems associated with Pradaxa side effects Among the reported adverse events were at least 582 deaths on Pradaxa.

This is the second year Pradaxa has topped the list of more than 700 drugs being monitored by the group, and Pradaxa has only been on the market in the United States for two full years.

Reports of Pradaxa Problems

Pradaxa (dabigatran) was introduced by Boehringer Ingelheim in October 2010, as the first member of a new class of anticoagulants promoted as a superior alternative to warfarin for stroke prevention, as it is easier to take and requires less medical monitoring.

By comparison, warfarin, which Pradaxa was designed to replace, only received 861 adverse event reports in 2012, with 56 deaths.

Xarelto (rivaroxaban), which is another new medication that is part of the same new class of anticoagulants as Pradaxa, ranked 10th among drugs most commonly associated with adverse events last year, with 2,081 reports and 151 deaths. The most common adverse events identified among users of all three anticoagulants was hemorrhaging, or uncontrolled bleeding

Boehringer Ingelheim has pointed to a number of studies that appear to show that Pradaxa is just as safe, if not safer, than warfarin (which is also sold under the brand name Coumadin). However, there are concerns that Pradaxa bleeding is more difficult to treat because warfarin’s anticoagulant effects can be countered with a dose of vitamin K. There is no known antidote, or reversal agent, for Pradaxa.

Despite the manufacturer’s safety claims, ISMP’s analysis of the adverse event reports found that Pradaxa side effects were more likely to result in patient death than warfarin side effects. The analysis indicated that 18% of Pradaxa adverse events resulted in the death of the patient, compared to only 7.2% of Xarelto cases and 6.5% of warfarin cases.

Report Criticizes FDA’s Defense of Pradaxa

The ISMP QuarterWatch report for the entire year of 2012 criticised the FDA’s handling of Pradaxa, indicating that the agency has “apparently intended to discount safety concerns” linked to Pradaxa.

The report notes that the FDA dropped a mandatory medication guide, and reversed an earlier decision and allowed Boehringer Ingelheim to claim Pradaxa is superior to warfarin. The report also notes that the FDA required an unusual boxed warning on Pradaxa in April, which stated that if patients stopped using the drug they could be at increased risk of stroke.

The ISMP report points out that the FDA’s Pradaxa boxed warning failed to mention that halting Pradaxa use decreased the risk of severe hemorrhage.

“The agency took several additional actions to reassure doctors and patients that growing number of adverse event reports did not signal an important risk,” the report states, going on to outline unusual FDA steps to support Pradaxa over the last two years. “The FDA’s many actions to discount mounting safety concerns about anticoagulant adverse effects remain unexplained.”

The ISMP investigators point out that Pradaxa bleeding incidents occur in older patients and are more likely to be fatal. The group suggests that a lower dose of Pradaxa and enhanced monitoring of kidney function could reduce bleeding events in older patients.

Pradaxa Lawsuits

Hundreds of Pradaxa lawsuits are currently pending in state and federal courts throughout the country, brought on behalf of former users who suffered severe and often fatal injuries. The complaints allege that the drug maker failed to adequately warn about the bleeding risk with Pradaxa or about the lack of a reversal agent.

In the federal court system, more than 1,500 cases are currently consolidated for pretrial proceedings as part of an MDL, or Multi-District Litigation, which is centralized before U.S. District Judge David R. Herndon in the Southern District of Illinois. As part of the coordinated litigation, a small group of cases are being prepared for early trial dates, known as “bellwether” cases. These early trials are designed to help the parties gauge how juries may respond to certain evidence and testimony that may be repeated throughout a large number of other cases.

At the time the MDL was established, there were only 21 cases pending in 11 different U.S. District Courts. However, as Pradaxa lawyers have continued to review additional lawsuits for individuals who suffered severe injuries from uncontrollable bleeding events, the number of complaints has continued to increase. More than 200 cases have been added to the MDL over the past three months.