Xarelto (rivaroxaban) is one of a number of “new generation blood thinners” or “novel oral anticoagulants” (NOACs) that have been developed over the past several years for the treatment of patients at risk for deep vein thrombosis (blood clotting).
In general, these medications prevent the formation of clots by inhibiting the action of biochemicals in the bloodstream that cause coagulation in the first place. While these medications have certain advantages over earlier treatments such as coumarins, they also pose a serious danger of fatal hemorrhaging.
Xarelto was first approved by the U.S. Food and Drug Administration in 2011. Over the next three years, there were thousands of adverse event reports on patients who had suffered fatal and near-fatal bleeding while on the medication. Despite these reports, the manufacturers have continued to engage in aggressive marketing campaigns, citing questionable, self-funded studies to support their claims that the product is “safe.”
Xarelto’s Mechanism of Action
Xarelto is what is known as a “Factor Xa (10-A) Inhibitor.” This is a biochemical substance (more accurately, an enzyme), produced in the liver, that plays an important role in blood clotting. Xarelto operates by disabling the production of Factor Xa. Specifically, Factor Xa formation is dependent upon Vitamin K, a group of compounds found in leafy greens as well as meat, cheese and eggs.
Under normal conditions, Factor Xa binds to a second enzyme, known as Factor Va (5-A), which forms the “prothrombinase complex.” When this happens, it converts a third enzyme, prothrombin, into thrombin – and this results in the formation of blood clots (hence the medical term “thrombosis”).
By comparison, coumarins act by preventing the action of Vitamin K. Since Vitamin K is necessary for the production of Factor Xa, thrombin cannot form in the presence of coumarins. The drawback to coumarin drugs is that it is necessary for patients to avoid eating many foods, particularly nutrient-dense leafy greens.
There are many interactions with other medications, which is always a serious concern with elderly patients who typically take anticoagulants. On the other hand, if a patient begins to experience serious, life-threatening bleeding, they can be treated with high doses of Vitamin K. This is not the case with Factor Xa inhibitors.
Xarelto Indications and Risks
Xarelto is specifically prescribed for patients who:
- suffer from non-valvular atrial fibrillation (irregular heartbeat) and are at risk for systemic embolism and stroke
- have undergone joint surgery in order to prevent deep vein thrombosis (DVT) that may cause pulmonary embolism
- are at risk for stroke due to acute coronary syndrome (a set of conditions that can result in a sudden reduction of blood supply to the heart)
Dosage is typically once a day with the evening meal.
Manufacturers of NOACs point out that their medications are easier to administer, require fewer doses, and have far fewer interactions with other medications. Expensive and time-consuming patient monitoring is not required to the same degree as it is when coumarin drugs are prescribed.
However, since Xarelto and similar medications prevent Factor Xa from performing its function in the first place, no amount of Vitamin K will help a patient who has begun hemorrhaging. Although an antidote has been under development, it has yet to receive FDA approval. At present, the only way to save a Xarelto patient from bleeding out is to administer emergency dialysis in order to eliminate the drug from the system as soon as possible.
Manufacturers of Xarelto Attempt to Downplay its Dangers
As evidence emerged about the dangers of Xarelto, Bayer and Janssen doubled down on their attempts to promote the product and even expand its market. In a press release dated September 1, 2015, Janssen parent corporation Johnson & Johnson announced the results from two “landmark real-world studies,” supporting the claim that “the use of rivaroxaban in day-to-day care is consistent with the safety profile observed in ROCKET-AF, the landmark Phase 3 study used by regulatory authorities worldwide to approve the medicine for the prevention of stroke in patients with non-valvular atrial fibrillation.”
When the drug was first under consideration for approval, FDA officials expressed doubts about the ROCKET-AF study. The specific concern was whether or not Xarelto would be as effective as the manufacturers claimed when used in accordance with labeling instructions. Subjects who participated in ROCKET-AF spent significantly less time at the “international normalized ratio” (INR). This is a measure of the length of time required to form a blood clot, used to measure the efficacy of oral anticoagulants. It was the opinion of the FDA at that time that the conditions of the study were insufficient to prove the effectiveness of Xarelto compared to coumarin drugs.
More recently, Johnson & Johnson cited a post-market safety surveillance (PMSS) study to support the claim that fatal bleed-outs among patients taking Xarelto were extremely rare, occurring no more than .01 percent of the time. It is worth noting that both ROCKET-AF and the PMSS study, titled XANAP, were funded by the same companies that manufacture and market Xarelto.
Independent Research Comes to Different Conclusions Regarding Xarelto Safety
Three other studies contradict the findings of ROCKET-AF and XANAP. The earliest of these, published in the journal Gastroenterology in July 2013, found that patients treated with Xarelto and similar NOACs were far more likely to suffer fatal gastrointestinal bleeding compared with those taking coumarin medications.
The following year, a study published in the Journal of the American Medical Association concluded that “treatment with rivaroxaban can be associated with severe, symptomatic liver injury.”
Then, in 2015, a retrospective cohort study appearing in the British Medical Journal concluded that patients faced a “twofold higher risk of bleeding with rivaroxaban [Xarelto] compared with warfarin.”
Unsurprisingly, neither Bayer nor Janssen have ever referred to these studies when making their claims.
Desperately Working to Preserve and Grow Profits
Bayer and Janssen have a great deal at stake in the impending litigation. With an aging population and greater longevity, the market for anticoagulant medications is expected to reach $15 billion by 2018 – and Xarelto stands to receive more than 20% of that amount.
Xarelto has been Bayer's top-selling product, generating $3.24 billion in revenues in 2016. At the same time, Xarelto is Janssen's third most lucrative medication, with nearly $2.3 billion in sales for 2016.
Despite the number of lawsuits and the weight of the evidence against them, Janssen and Johnson & Johnson have submitted an application to the FDA, seeking approval for a low-dose version of Xarelto. That application is currently under review.
More than 25,000 cases are pending against Bayer and Janssen involving Xarelto. Plaintiffs allege that the companies failed to warn doctors and patients that the drug could cause irreversible internal bleeding, and that a substitute medication was just as effective at reducing clots but without the life-threatening danger of excessive blood loss.
For extensive information on these court proceedings, visit our Xarelto Lawsuit Page. This page describes in detail the litigation pending against Janssen Pharmaceuticals and Bayer AG, and how someone injured by Xarelto can participate in the court proceedings and receive compensation for their injuries.