New Blood Thinner Reversal Agent Won’t Work With Pradaxa, Xarelto

Federal drug regulators have approved the use of a reversal agent for anticoagulation therapy, which will be marketed as Kcentra. The drug is designed to help prevent patients given Coumadin or its generic equivalent, warfarin, from bleeding to death. However, the reversal agent will not work with a newer class of anticoagulants, including Pradaxa and Xarelto, which have been linked to a large number of problems involving uncontrollable bleeding.  

On April 29, the FDA announced it was approving Kcentra, a CSL Behring drug, for the urgent reversal of vitamin k antagonist (VKA) blood thinners. To date, the only other product ever approved for this use was plasma, but doctors have been using vitamin K for years to treat patients who suffer uncontrolled bleeding after being placed on a warfarin regimen.

Usually, doctors give bleeding warfarin patients vitamin K and large doses of plasma to reverse the blood thinning effects of the anticoagulant and stop bleeding problems that may develop. However, Kcentra would replace the plasma, and would not need to be thawed or matched to a patient’s blood type.

“The FDA’s approval of this new product gives physicians a choice when deciding how to treat patients requiring urgent reversal of VKA coagulation,” said Dr. Karen Midthun, director of the FDA Center for Biologics Evaluation and Research. “Kcentra is administered in a significantly lower volume than plasma at recommended doses, providing an alternative for those patients who may not tolerate the volume of plasma required to reverse VKA anticoagulation.”

Pradaxa Bleeding Risks

While warfarin has been the mainstay anticoagulation therapy for prevention of strokes for decades, in recent years a new class of medications, known as direct thrombin inhibitors, have increased in popularity because they require less monitoring during therapy.

Pradaxa (dabigatran) was the first member of this class approved in the U.S., introduced by Boehringer Ingelheim in October 2010. It has quickly grown to become a blockbuster medication, and is the most widely used of the class. Xarelto (rivaroxaban) is a related drug that is distributed jointly by Bayer and Johnson & Johnson.

Both drugs have been linked to a surprising number of adverse event reports since they were introduced, involving doctors who were unable to control bleeding problems with Pradaxa or Xarelto that may develop. Kcentra is not an effective reversal agent for these new generation blood thinners and is not seen as a solution to these problems.

During 2011, the first full year that Pradaxa was on the market in the United States, the Institute for Safe Medication Practices (ISMP) found that adverse event reports involving Pradaxa problems surpassed all other medications regularly monitored by the group. The FDA received at least 3,781 reports involving serious injuries associated with the use of Pradaxa during 2011, including 2,367 reports of hemorrhage and 542 patient deaths.

More than 200 Pradaxa bleeding lawsuits have been filed against Boehringer Ingelheim, alleging that the drug maker failed to adequately warn consumers or the medical community about the risk of serious bleeding and the lack of a reversal agent to stop hemorrhaging that may develop.

Xarelto is distributed jointly by Bayer and Johnson & Johnson, and the companies indicated earlier this year that they are working on the creation of an Xarelto reversal agent. However, it will likely not be available until later this year. Such an antidote would provide a substantial competitive advantage for Xarelto over Pradaxa.