Xarelto

What No Xarelto Reversal Agent Means for Patients and Physicians

Xarelto reversal

Not long ago, warfarin (brand name Coumadin®) was the only available prescription anticoagulant. Warfarin effectively cornered the blood thinner market for nearly 60 years. But between 2007 and 2011, warfarin treatment visits dropped from 2.1 million quarterly to just 1.6 million. That’s because drug manufacturers introduced four new anticoagulants within the last 10 years. Xarelto® is one of the newer drugs stealing some of warfarin’s patients. Despite no Xarelto reversal agent for treating emergency bleeding cases, this new anticoagulant quickly became a top-selling prescription. There’s no need for regular blood monitoring or frequent follow-up visits, so many doctors now prescribe Xarelto over warfarin. Still, some doctors are hesitant to drop warfarin for a newer blood thinner with such a potentially risky side effect. And according to recently published medical studies, those physicians may be right.

No Known Xarelto Reversal Agent Makes Bleeding Episodes More Dangerous

Longstanding blood thinner warfarin has a reversal agent. During an emergency bleeding episode, doctors simply give the patient Vitamin K. Vitamin K reverses warfarin’s blood-thinning effects in order to help blood clots form. A patient can thus avoid bleeding out, which often saves the person’s life. Xarelto currently has no antidote available for emergency bleeding episodes. So, taking this newer prescription blood thinner puts individuals at increased risk of an extremely dangerous and possibly fatal outcome.

What A Lack of Antidote Means for Xarelto Patients

The solution seems obvious: if Vitamin K reverses warfarin’s blood-thinning effects, why won’t it work for Xarelto? What reversal agents currently exist for other new wave anticoagulant medications? Despite marketing Xarelto as a “blood thinner” medication, it doesn’t actually thin your blood. Xarelto actually prevents a protein-based component called Factor Xa from clotting your blood. Xarelto does a good job of preventing blood clots and pulmonary embolisms (among other nasty complications patients hope to avoid). But during a serious bleeding episode, Xarelto patients can bleed out and die.

Dr. Charles Pollack, emergency physician at Thomas Jefferson University Hospital in Philadelphia, says of these major bleeding events: “It may be uncommon, but they’re memorable when they happen.” He explains that physicians feel insecure about prescribing Xarelto over anticoagulants with effective reversal agents. Blood thinners with reversal agents include Pradaxa as well as warfarin/Coumadin. Dr. Mariell Jessup, cardiologist at the University of Pennsylvania Medical Center, says: “I have many physicians, particularly surgeons, who hate these drugs. [the four new blood thinners] They’re frightened of them because they’ve had to deal with the consequences of somebody coming in with trauma.” With no way to clot a Xarelto patient’s blood, serious cuts or surgery can cause uncontrollable internal or external bleeding.

The Hunt for a Xarelto Reversal Agent

In 2015, Portola Pharmaceuticals applied for Food and Drug Administration approval of a drug called AndexXa™ (andexanet alfa). AndexXa would quickly reverse anticoagulation effects for Xarelto and Eliquis (apixaban), two Factor Xa inhibitors. Physicians and Portola in particular were excited about the prospect of having a FDA-approved antidote for newer anticoagulants. Unfortunately, their excitement was short-lived.

The FDA put AndexXa on an accelerated approval pathway as an orphan drug in early 2016. All parties were eager to find a safe, effective antidote for the newest Factor Xa inhibitor drugs. But in August 2016, the FDA turned down an accelerated approval timeline for the drug. The agency sent Portola a letter asking for additional manufacturing information and data to support their request to include direct Factor Xa inhibitor edoxaban and indirect inhibitor enoxaparin on AndexXa’s label. The letter also indicated a need to review clinical amendments to post-marketing commitments submitted by Portola.

Portola still stresses the need for an approved Xarelto reversal agent. In a press release, Portola states 1%-4% of patients treated with Factor Xa inhibitors (including Xarelto) may experience major bleeding: “In the United States, more than 80,000 patients treated with oral Factor Xa inhibitors were admitted to the hospital due to bleeding during 2015.” That number rises to 100,000 patients if those treated with injectable Factor Xa inhibitor enoxaparin in 2015 are included. Despite the obvious need, no Xarelto reversal agent currently exists. Therefore, the risk of bleeding out is still a major concern for all Xarelto patients. After receiving the FDA’s response, Portola’s stock value fell by 12%. There’s no way to predict how soon AndexXa might be approved, but it could take seven years.

What A Lack of Xarelto Reversal Agent Means for Prescribing Physicians

The FDA’s refusal to approve AndexXa makes Xarelto a risky drug to prescribe. Still, other factors come into play beyond needing an FDA-approved antidote for emergency bleeding scenarios. Dr. Sanjay Kaul, cardiologist at Cedars-Sinai Medical Center in Los Angeles, expressed extreme concerns about Xarelto. Dr. Kaul says he received a dozen calls from colleagues about patients bleeding after taking a new wave blood thinner called Pradaxa. He subsequently found that many of these physicians didn’t test each patient’s kidney function before prescribing Pradaxa.

When kidneys are weak, medicine excreted by the organ instead builds up to unsafe levels in the patient’s bloodstream. And kidneys eliminate two-thirds of Xarelto from the patient’s body, internal bleeding risks increase significantly. “What really compounds the matter is the lack of a specific antidote to reverse life-threatening bleeding,” said Dr. Kaul, who served on independent panels advising the FDA about Xarelto and Pradaxa. He urges other physicians to consider the risks associated with each new anticoagulant drug before prescribing them for patient use.

What the Lack of Xarelto Reversal Agent Means for Patients

Because no Xarelto reversal agent currently exists, bleeding risks remain extremely high. While emergency situations are rare, if one does occur, the patient risks serious injury or death. Since surgeons cannot help clot a patient’s blood at expected normal rates, the patient may bleed out. Until the FDA approves AndexXa or another viable antidote, Xarelto’s adverse reaction risks remain high. If your doctor recommends Xarelto, ask for another blood thinner (like warfarin or Pradaxa) with an effective reversal agent.

If you or a loved one suffered from blood clots, uncontrolled internal bleeding or death while taking Xarelto, you may be eligible for compensation. Fill out your free Xarelto claim review form now and an experienced attorney will contact you about your case.