The blood thinner medication Xarelto (generic: rivaroxaban) has recently been linked to irreversible and potentially fatal bleeding events, hemorrhage, blood clots and other serious side effects.
Update: J&J, Bayer Ordered to Pay $28 Million in Xarelto GI Bleeding Lawsuit
December 6, 2017 – Bayer AG and J&J have been found liable and ordered to pay nearly $28 million to a woman who claimed Xarelto caused her to develop severe internal bleeding injuries. Plaintiffs secured a much-needed win the Xarelto litigation, as Bayer and J&J had emerged victorious in the previous 3 bellwether trials.
What is Xarelto?
Manufactured and marketed in a joint partnership between Jansen Pharmaceuticals (a Johnson & Johnson company) and Bayer HealthCare AG, Xarelto is an anticoagulant blood thinner designed to prevent the formation of blood clots. Xarelto was approved by the U.S. Food & Drug Administration (FDA) in July 2011 for the prevention of a type of blood clot known as deep vein thrombosis (DVT), a condition that commonly occurs after certain types of surgeries. The drug is also commonly prescribed to reduce the risk of stroke in patients with a certain type of heart rhythm disorder. Xarelto belongs to a class of drugs known as factor Xa inhibitors, which includes the much-troubled Pradaxa (generic: dabigatran).
‘ROCKET’ Safety Study
The largest clinical trial conducted to date on Xarelto was ROCKET (Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial). This study looked at data on over 14,000 patients and compared Xarelto to warfarin. ROCKET determined that Xarelto was no more effective than warfarin, and that the health risks associated with the drugs were similar. The most commonly reported side effect was internal bleeding, with rates similar to that of warfarin. However, Xarelto caused fewer brain bleeds and more bleeding events in the stomach and intestines.
Many experts have questioned the safety of Xarelto as a result of internal bleeding reports and the lack of antidote when these events occur. The FDA staff gave a negative review of Xarelto for patients with atrial fibrillation (afib), citing multiple problems with the ROCKET study. The agency requested that Janssen conduct additional research to better understand the link between Xarelto, internal bleeding and stroke.
In January 2012, Reuters reported that the U.K.’s National Institute for Health and Clinical Excellence (NICE) had refused to recommend or approve Xarelto for use in state health services until Bayer can provide more safety data on the drug. Other medications battling with Xarelto for dominance in the highly lucrative anticoagulant market include:
- Eliquis (generic: apixaban), made by Pfizer and Bristol-Myers Squibb. In September 2011, data was released which found that Eliquis causes fewer deaths and less bleeding than warfarin.
- Pradaxa (generic: dabigatran), manufactured by Boehringer Ingelheim.
- Lixiana (edoxaban), manufactured by Daiichi Sankyo.
Xarelto & Stroke
Blood clots in the brain can cause a transient ischemia attack (TIA), also known as a “mini-stroke,” which may precede a stroke. If blood flow is obstructed for more than a few seconds, the brain begins being deprived of blood and oxygen. Brain cells can die, causing permanent damage to the organ. Xarelto labels contain a boxed warning indicating that there is an increased risk of stroke after discontinuing use of the drug for the treatment of non-valvular afib. Increased stroke rates were observed during the transition from Xarelto to warfarin in clinical trials in afib patients.
Signs and symptoms of a Xarelto stroke may include:
- One side of the face may droop or become numb
- Sudden numbness or weakness in an arm or a leg
- Slurred speech or speech that is difficult to understand
- Sudden trouble seeing in one or both eyes
- Sudden trouble walking
- Sudden dizziness, loss of balance or coordination
- Sudden severe headache with no known cause
Xarelto has been linked to an increased risk for internal bleeding events. Signs and symptoms of Xarelto-induced internal bleeding may vary, depending on the location of the bleeding, and what body functions are affected. Symptoms of internal bleeding may include:
- unusual bleeding
- discolored urine (blood in the urine)
- red or black-colored stool
- coughing up blood
- vomiting blood that looks like coffee grounds
- frequent nose bleed or gum bleeding
- weakness and swelling in the extremities
According to a new study conducted by researchers in Australia, Xarelto presents less of a risk of bleeding in the brain than Coumadin (warfarin) when given to patients with atrial fibrillation, but like Pradaxa, Xarelto may cause more serious bleeding events that could be difficult to treat. The FDA has announced that it is currently in the process of evaluating bleeding events in patients being treated with Xarelto to determine whether the risks outweigh the benefits of the drug.
Although excessive bleeding events are the most commonly reported serious side effect associated with Xarelto, there has been increasing concern about the development of blood clots in patients who are administered Xarelto as a prophylaxis. These patients tended to be a younger group [median age 66] who took Xarelto after hip or knee replacement surgery. According to a report issued by the Institute for Safe Medication Practices (ISMP), of the 356 adverse events reported in the first quarter of 2012, at least 158 cases of blood clots or thromboembolic events were reported to the FDA.
Signs and symptoms of a Xarelto blood clot may include:
- exhaustion or unexplained fatigue
- redness, inflammation or varicose veins
- shortness of breath
- chest pain or pain with deep breathing
- fever or sweats
- dizziness or fainting
- increased heart rate
- unexplained cough
- asymptomatic (no symptoms)
- bloody mucus with worsening cough
JAMA Study Investigates Blood Clot Treatment Strategies
A September 2014 study published in the Journal of the American medical Association (JAMA) found that most treatment options for blood clots in veins (venous thromboembolism) were equally safe and effective, yet major bleeding events occurred more often in patients treated with anticoagulants like Xarelto. Researchers conducted 45 randomized trials on 44,989 test subjects, and found that 0.49% of Xarelto users suffered a major bleeding event during the first three months of treatment, compared to just 0.29% with Eliquis. The study’s authors concluded that, except for a UFH-vitamin K antagonist combination, all other treatment strategies had similar bleeding risks.
Xarelto Side Effects
In addition to having the potential to cause blood clots and serious internal bleeding events, Xarelto has also been associated with a number of other side effects including:
- brain hemorrhage
- epidural hematoma
- gastrointestinal bleeding
- pulmonary embolism
- severe allergic reactions
- bloody or black, tarry stools
- coughing up blood
- dark urine
- sore throat
- pain or new drainage at wound sites
- pink or red urine
- red, swollen, blistered, or peeling skin
- stiff, sore, hot, or painful joint
- unexplained swelling
- unusual or prolonged bruising or bleeding
- vomit that looks like coffee grounds
- yellowing of the skin or eyes (jaundice)
- and more
Xarelto Bleeding Risk Increased in Acutely Ill, ACS Patients: Study
In November 2013, a study published in Medscape identified a link between Xarelto and a nearly 3-fold increased risk of bleeding in acutely ill patients, as well as a 4-fold increased risk of major bleeding in patients diagnosed with Acute Coronary Syndrome (ACS). These findings were based on data from four dozen clinical trials involving Xarelto, Pradaxa, Eliquis, Lixiana and darexaban, all of which have been approved since 2010. The study’s authors wanted to know how these drugs performed against each other, as well as how they compared to warfarin and heparin, staple anticoagulants that have been in use for more than 50 years in the U.S.
Bleeding events associated with the new drugs included:
- Hip surgery – 1.43-fold increased rate of major bleeding
- ACS – 3.27-fold increased rate of major bleeding
- Medically ill thromboprophylaxis – 2.79-fold increased rate of major bleeding
Are Xarelto Lawsuits Being Filed?
- February 2014: a lawsuit was filed on behalf of Virginia G. Stuntebeck, a Kentucky woman who allegedly experienced severe internal bleeding after taking Xarelto. That case is: Stuntebeck v. Janssen Research & Development LLC et al, Case Number 140201754; Court: Philadelphia Court of Common Pleas.
- May 2014: a wrongful death lawsuit was filed against Janssen and Bayer which stated that Xarelto caused the death of Mattie Edgin, who allegedly died after taking the drug. Edgin’s niece Della Wise, who filed the complaint, said that Xarelto was “fervently marketed … with no regard to the accuracy and misrepresentations of their misleading marketing.”
Wise accuses the companies of falsely claiming that Xarelto users do not need to undergo routine testing for internal bleeding or blood clots. She also noted that Xarelto does not have a reversal agent, unlike warfarin, which can be counteracted with a single dose of Vitamin K when bleeding events occur. The lawsuit seeks punitive damages, including fraud, wrongful death, consumer law violations, negligence, failure to warn, product liability, unreasonable marketing of a dangerous drug, and breach of warranty.
- June 2014: The wife of a man who allegedly bled to death after taking Xarelto filed a lawsuit against Janssen for failing to warn that the drug can cause uncontrollable bleeding events. The complaint was filed in federal court in Florida by Nancy Packard, on behalf of her husband, William N. Packard, Jr., who started taking Xarelto in January 2012 for the treatment of afib.
After using the drug for approximately 6 months, Mr. Packard developed bleeding in his brain and was hospitalized. Doctors were unable to stop the bleeding, even after drilling a burr hole in his skull, and Packard died on June 28, 2012. According to the complaint:
“Defendants failed to adequately warn about the lack of an antidote to reverse uncontrolled bleeding caused by Xarelto. Defendants merely indicated that there was a risk for bleeding and side-stepped the important issue of reversing the effects of Xarelto should a bleed occur. Other safer alternatives to Xarelto® have an antidote that can reverse uncontrolled bleeding.”
That case is: Nancy Packard v. Janssen Research & Development LLC et al; Case Number 9:14cv80831; U.S. District Court for the Southern District of Florida.
- October 9, 2014: An 87-year-old man who allegedly experienced severe internal bleeding after taking Xarelto filed a lawsuit against Janssen and Bayer. The plaintiff began using the drug on his doctor’s advice in early 2012, and suffered a gastrointestinal bleed on October 15, 2012. The lawsuit claims his injury was a direct result of Xarelto side effects, and seeks compensation for personal injuries, pain and suffering, and emotional distress.
ISMP QuarterWatch Links Xarelto to 15,000 Adverse Event Reports in 2016
July 18, 2017 – Xarelto was linked to at least 15,043 adverse event reports last year, according to the latest ISMP QuarterWatch Report. A total of 21,996 injuries were associated with the entire class of blood-thinners, nearly 70% of which were tied to Xarelto.
Bayer, J&J Misrepresented Xarelto Risks, Lawsuits Claim
July 12, 2017 – Two men from New York have filed separate lawsuits against Bayer and Janssen Pharmaceuticals alleging that Xarelto caused “life-threatening bleeding” and “other severe and personal injuries.” Plaintiffs Thomas Walsh and Joseph Roman further allege that Bayer and Janssen hid their knowledge of these “serious and dangerous side effects,” including life-threatening bleeding events, which were caused by a lack of adequate clinical trials and studies.
First Xarelto Trial Kicks Off in New Orleans
April 24, 2017 – The first of 4 bellwether trials alleging bleeding side effects from Xarelto is now underway in Louisiana federal court. The complaint was filed by Joseph Boudreaux, who claims he experienced severe internal bleeding less than a month after taking Xarelto for the first time. His injuries required a week-long stay in an ICU, numerous blood transfusions and heart procedures, according to the lawsuit.
Xarelto Bellwether Trials Begin in Louisiana
April 4, 2017 – Judge Eldon Fallon is set to begin hearing the first Xarelto bellwether trials later this month, and the cases are being watched very closely as outcomes could help to determine future rulings. The first trial is scheduled to begin on April 24, with another beginning each month until July. Since the cases involve complex pharmaceutical litigation, each trial could last up to 8 weeks before a jury returns a verdict.
Xarelto Multidistrict Litigation
The U.S. Judicial Panel on Multidistrict Litigation (JPML) has agreed to centralize all federally-filed Xarelto Lawsuits into a single proceeding to be established in the U.S. District Court, Eastern District of Louisiana. At least 21 lawsuits have been filed in federal court alleging that Xarelto caused plaintiffs to suffer life-threatening internal bleeding events and other serious complications, according to a transfer order issued Dec. 12.
Xarelto Associated with Increased Bleeding, Mortality Compared to Pradaxa
October 7, 2016 – Xarelto has been linked to an increased risk of bleeding in elderly patients treated for nonvalvular atrial fibrillation (a-fib) compared with Pradaxa (diabigatran), according to a new study published in JAMA Internal Medicine. In addition to the increased bleeding associated with Xarelto, the study found that the drug reduced risk of thromboembolic stroke and increased risk for mortality compared to Pradaxa. However, the increase in intracranial hemorrhage with Xarelto outweighed reductions in stroke, according to David J. Graham, MD, MPH, from the FDA’s Center for Drug Evaluation and Research.
Xarelto Bleeding Lawsuit Filed in Illinois
September 6, 2016 – A group of 10 people who claim Xarelto caused severe bleeding have filed a products liability lawsuit against Bayer and Janssen Pharmaceuticals. Plaintiffs have charged the defendants with 9 counts of misconduct ranging from fraud to wrongful death for failing to adequately warn about the risk of Xarelto side effects. The complaint was filed in St. Clair County Circuit Court, Illinois, under case number 15-L670.
European Labels Updated to Include Guidance for A-Fib Cardioversion
Jan. 20, 2015 – Bayer today announced changes to Xarelto product information in Europe, according to the European Medicines Agency (EMA). The label update provides doctors with information regarding the clinical utility of Xarelto in patients with non-valvular atrial fibrillation who require cardioversion, and is based on the CHMP opinion issued Dec. 2014.
While there is currently no known antidote or reversal agent to stop bleeding events with Xarelto, a drug called Andexanet alfa is being developed that may serve this purpose. The drug is now undergoing late-stage clinical trials, and is expected to gain approval from the FDA in mid-2016.
Has There Been a Recall?
Although many lawsuits have called for Xarelto to be pulled off the market until an antidote or reversal agent to stop bleeding events can be developed, it does not appear likely that the FDA will require the manufactures to recall the drug. Instead, a black box warning may be added to Xarelto labels informing users about the risk of hemorrhage associated with its use. Informing potential users and the medical community about the lack of an antidote and the importance of monitoring users during treatment to evaluate their risk of hemorrhages may have prevented many injuries and deaths among Xarelto users.