Study Indicates Potential Pradaxa Antidote—Nearly 2,000 Lawsuits Pending

Shortly after the FDA approved the anti-coagulant “Pradaxa” in October 2010, patients started complaining of serious side effects.

Prescribed to those with non-valvular atrial fibrillation to reduce risk of stroke, Pradaxa was hailed as the more convenient option to warfarin (Coumadin)—the leading anti-coagulant for many decades— because it does not require regular blood monitoring or dietary changes. Doctors later discovered, however, that it also had no readily available antidote—no way to stop excess bleeding should it occur.

Now, a new study has identified a potential solution to the problem, but more research is necessary  before a remedy is available. Meanwhile, patients are still at risk of serious gastrointestinal bleeds and even death.

Manufacturer Defending a Number of Lawsuits

According to new data from Boehringer Ingelheim, manufacturer of Pradaxa, scientists have discovered a protein that may help to reverse the effects of the drug. Though all anti-coagulants carry a risk of excessive bleeding, patients on warfarin can receive vitamin K injections, which reverse the effects and allow the blood to clot, stopping emergency bleeding. Pradaxa, however, contains no such antidote, making bleeding events much more dangerous.

The Institute for Safe Medication Practices noted in the first quarter of 2011 that Pradaxa was linked with more adverse event reports than all but one other drug. That same year, over 500 patients died because of problems reportedly linked to Pradaxa. So many people have filed lawsuits against the company because of these types of injuries that the U.S. Judicial Panel on Multidistrict Litigation (JPML) consolidated all federal lawsuits into the Southern District of Illinois in August 2012 for coordinated proceedings.

Study Results Show Some Promise

Typically, Pradaxa helps reduce blood clotting by blocking the action of an enzyme called “thrombin.” Thrombin breaks apart a protein called “fibrinogen,” which typically glues blood platelets together to form blood clots. By breaking fibrinogen apart, the drug stops the clotting process.  In a randomized, double blind, placebo-controlled study of 145 healthy male volunteers, researchers evaluated the safety and performance of a type of protein called “fully humanized antibody fragment (Fab).” Boehringer Ingelheim presented its research findings at the American Heart Association’s Scientific Sessions 2013. The study reported the Fab protein helps block the function of Pradaxa.

According to the new study, Fab keeps Pradaxa from attaching to thrombin, stopping its action and allowing blood to clot again. Researchers had male volunteers take Pradaxa for four days, then measured the time it took for their blood to clot before and after several different doses of Fab. Results showed:

• Reversal of the blood thinning effect was complete and sustained in 7 of 9 subjects who received the two-gram dose, and in 8 out of 8 of those who received the 4-gram dose.
• The one-gram dose also reversed blood thinning and allowed clotting, but began to fail after 30 minutes.
• Side effects included headache, migraines, and reddening of the skin.

The Need for More Research

Though the results look promising, this is a very small study. The results are also preliminary, and have not yet been evaluated by independent researchers. Additional testing on the potential antidote is scheduled to begin in 2014.

Meanwhile, early bellwether trials in the Pradaxa MDL are scheduled to start in August 2014. Currently, more than 1,800 cases allege Boehringer Ingelheim did not do enough to warn doctors and patients about the risks of Pradaxa, failed to conduct adequate safety studies, and failed to find an antidote before marketing the drug to consumers.