Xarelto Bleeding Reversal

 Lawsuits recently emerged after the FDA found an association between the implants and a rare form of cancer called lymphoma. Many victims filed a claim after they started suffering from serious medical conditions that included, in some instances, anaplastic large cell lymphoma (ALCL), a malignant form of leukemia. According to plaintiff’s accusations, Johnson and Johnson and its subsidiary Mentor Worldwide failed to warn about the danger of hazardous chemicals leaking from the silicone breast implant into its capsule.

The absence of a Xarelto antidote

There’s no real Xarelto antidote available that provides an effective bleeding reversal. So what a person could do whenever a bleeding to death accident happens? Seeking emergency treatment is mandatory, but even in a hospital setting, there’s very little that doctors could do. Vitamin K is totally ineffective due to the different mechanism of action. Other standard treatment options such as administration of prothrombin complex concentrate (PCC) or fibrinogen are equally ineffective and have been ruled out by several clinical trials.

Even dialysis is not an adequate solution since it does not flush the drug out of the patient’s body because rivaroxaban is highly bound to plasma proteins. Waiting or providing blood transfusions is the only treatment option available for physicians.

Is it thus actually possible to save a patient when a serious internal bleeding is threatening his life? Although an antidote has been required for many years, a truly effective treatment strategy is not still available. Many guidelines tried to address the best way to avoid the direct consequences of a hemorrhage, but a real definitive solution has not been found, yet.

A new future antidote?

Recently, the U.S. Food and Drug Administration (FDA) granted approval for an antidote to reverse the effects of Xarelto’s close “brother” medication Pradaxa (dabigatran). This antidote, called Praxbind (idarucizumab) however, is a monoclonal antibody fragment, meaning that it possesses a very specific action mechanism, so it is effective only for Pradaxa itself.

Two different molecules have been investigated in the past as possible rivaroxaban antidotes and are currently under trial to assess their effectiveness and safety. The first potential reversal agent is Ciraparantag (PER977) manufactured by Peroshpere and Daiichi Sankyo. Ciraparantag should act by reversing the blood thinner’s anticoagulant activity after just a single intravenous administration, not requiring a continuous infusion in order to keep the reversal maintained. Although Ciraparantag has been originally engineered to reverse the actions of several heparins and the other Novel Oral Anticoagulant (NOAC) Edoxaban, the manufacturer intended to seek FDA approval as an antidote for rivaroxaban as well.

The second bleeding reversal agent is Andexanet Alfa (PRT064445), manufactured by Portola Pharmaceuticals who is pursuing an Accelerated Approval pathway to guarantee its release on the market. Andexanet acts by binding to Factor Xa Inhibitors such as Xarelto and preventing them from exerting their action on blood coagulation. The ability of Andexanet to restore the normal hemostatic processes in patients under treatment with various NOACs is being investigated in two pivotal studies called ANNEXA-A and ANNEXA-R. Although Andexanet was able to show a significant suppression of the anticoagulating action of Factor Xa Inhibitors in just a few minutes, to achieve its full activity it still required a sustained 2-hour infusion.

On August 16, 2016, the FDA refused to grant approval to Portola’s new antidote and rejected the application. The company, however, announced that its intention is to resubmit the reversal agent to the regulator before the end of the current year.

In the meanwhile, the lack of an effective antidote forced many patients to sustain significant injuries because of the side effects of this medication. Many plaintiffs filed a bleeding lawsuit to ask Bayer for compensation for the personal damage they suffered. Xarelto lawyers ask the courts to hold Bayer responsible for releasing to the marked an unsafe drug that lacks a proper antidote to prevent life-threatening consequences.