Anticoagulant Antidotes: A Safety Requirement

Blood thinners, or anticoagulants, interfere with the body's clotting mechanisms in an effort to decrease the risks of clot, stroke, embolism and deep vein thrombosis. Though they can and do help many patients, anticoagulants can cause serious bleeding. Without a way to reverse the effects of anticoagulants, patients using the therapy would be left in a very precarious position. They would have to weigh the advantages of decreased clotting and stroke with the small but real risk of experiencing a life-threatening bleeding event with no available remedy.

Current Anticoagulants Didn't Always Have Antidotes

Blood thinners currently available in the United States have antidotes, but that wasn't always the case. Reversal agents for old-style blood thinners like warfarin and heparin have existed since the early 1900s. But newer drugs like Pradaxa and Xarelto were initially launched without antidotes, causing a number of serious bleeding events and deaths.

Many regulators and physicians believed these newer drugs represented an overall improved safety profile. They would not require constant monitoring and adjustment of dosages, nor would they have such a narrow effective range. Patients could take them less frequently, and that would improve the rates of prescription compliance. These positives seemed substantial enough for the FDA to initially approve the new generation of anticoagulants without antidotes.

Pradaxa and Xarelto Were Launched Without Antidotes

Pradaxa was launched in 2010, followed just shy of a year later by Xarelto. Neither had an antidote at the time of initial drug approval, and both quickly racked up thousands of serious adverse event reports, including patient deaths. Patients could have opted for the less convenient option of warfarin. It would have required more effort, but emergency room physicians would have been able to reverse it in the event of serious bleeding.

According to the United States Food and Drug Administration, adverse event reports for Pradaxa declined by almost 50% year over year after the launch of the blood thinner's antidote, Idarucizumab. It was on the market for less than five years before the antidote was introduced. On the other hand, Xarelto's manufacturer Janssen Pharmaceuticals never developed an anticoagulant antidote. Instead, small company Portola Pharmaceuticals took almost seven years to gain approval for its Xarelto antidote, Andexanet. In the meantime, hundreds of thousands of patients experienced dangerous bleeding events without a way to treat them.

Patients Should Be Clearly Informed If Anticoagulants Lack Antidotes

Thousands of patients and their family members have filed Xarelto and Pradaxa lawsuits, claiming they weren't adequately informed of the risks prior to taking the drug. Their outrage is understandable. When physicians and regulators know that anticoagulants cause serious bleeding events, no regular citizen expects these drugs to gain FDA approval without a way to restore normal clotting. They especially don't anticipate needing to read the fine print in order to learn that fact.

In a notable Xarelto lawsuit, plaintiff Kevin Cooney claimed he did not receive adequate warning of the bleeding possible with the drug. He suffered substantial internal bleeding while taking Xarelto but ultimately lost his case. Despite similar verdicts in other cases, Johnson & Johnson and Janssen Pharmaceuticals announced a $775 million settlement to resolve the remaining 25,000+ Xarelto lawsuits in March 2019.

Hopefully, the FDA will choose not to approve future anticoagulants without antidotes, because such drugs put patients at potentially unnecessary risk. And if regulators see a compelling reason to approve a next-generation anticoagulant without an antidote, hopefully, they will require full disclosure and documentation of informed consent, much like they recently did with the Essure birth control device.