Xarelto

Xarelto (rivaroxaban) is a blood thinner that is commonly used to prevent blood clots. Xarelto was approved for medical use in the United States in 2011. However, since that time thousands of patients have reported internal bleeding injuries, often resulting in hospitalization and death.

History of Xarelto

Rivaroxaban (Xarelto) was invented in Bayer’s Wuppertal laboratories and is being jointly developed by Bayer HealthCare and Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Xarelto was first approved for marketing authorization in Canada in September 2008 to prevent venous thromboembolism (VTE) in people who have undergone elective total hip replacement or total knee replacement surgery.

In September 2008, the European Commission also granted marketing authorization of Xarelto to prevent VTE in adults undergoing knee or hip replacement.

FDA Approval of Xarelto

On July 28, 2008, Bayer submitted a new drug application to the Food and Drug Administration (FDA) for rivaroxaban (Xarelto) as a novel anticoagulant taken as one tablet, once daily. “It seeks approval for the use of rivaroxaban in the prevention of deep vein thrombosis and pulmonary embolism in patients undergoing hip or knee replacement surgery.”

On March 19, 2009, the FDA’s Cardiovascular and Renal Drugs Advisory Committee determined Xarelto had a favorable risk-benefit profile for the prophylaxis of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients undergoing hip replacement or knee replacement surgery. The advisory committee agreed by a 15 to 2 vote.

On January 5, 2011, a New Drug Application (NDA) was submitted for rivaroxaban (Xarelto)for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

On July 1, 2011, the FDA approved Xarelto for prophylaxis of DVT, which may lead to PE in adults who undergo hip replacement or knee replacement surgery.

On November 4, 2011, the FDA also approved Xarelto for stroke prevention in people with non-valvular atrial fibrillation.

On November 2, 2012, the FDA expanded the use of Xarelto to treat and reduce the recurrence of blood clots.

The Intended Use of Xarelto

Xarelto is a factor Xa inhibitor. The primary indications of Xarelto are:

• To reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation;
• For the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), and for the reduction in the risk of recurrence of DVT and of PE; and
• For the prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Xarelto is taken as a tablet by mouth. For treatment of DVT and PE, Xarelto is generally taken twice daily with food for the first 21 days for the initial treatment of acute DVT or PE. After the initial treatment period, 20 mg is generally taken orally once daily with food for the remaining treatment and the long-term reduction in the risk of recurrence of DVT and of PE.

For prophylaxis of DVT following hip or knee replacement surgery, Xarelto is generally taken once daily with or without food. This usually continues for 35 days after a hip replacement surgery and for 12 days after knee replacement surgery.

For nonvalvular atrial fibrillation, Xarelto is generally taken once daily with the evening meal.

Patients should follow the directions on the prescription label carefully and ask their doctor or pharmacist to explain anything they do not understand. Patients should not stop taking Xarelto without talking to their doctor. If you stop taking Xarelto, your risk of a blood clot may increase.

How Xarelto Treats These Conditions

Rivaroxaban prevents blood clots by inhibiting free Factor Xa prothrombinase activity. It does not have a direct effect on platelet aggregation. Instead, it indirectly inhibits platelet aggregation induced by thrombin. This decreases thrombin generation which reduces platelet aggregation. Rivaroxaban inhibits both free and clot-bound Factor Xa and Factor Xa in the thrombinase complex.

General Side Effects of Using Xarelto

There are a number of possible side effects which may be related to taking Xarelto. Side effects may be serious and you should call your doctor immediately if you experience any of these symptoms. Side effects may include:

• bloody, black, or tarry stools
• pink, or brown urine
• coughing up or vomiting blood or material that looks like coffee grounds
• frequent nosebleeds
• bleeding from your gums
• heavy menstrual bleeding
• weakness
• tiredness
• headache
• dizziness or fainting
• blurred vision
• pain in arm or leg
• rash
• itching
• difficulty breathing or swallowing
• hives
• pain or swelling at wound sites
• muscle spasm

Contraindications

Contraindications refer to situations where a drug should not be used. Contraindications involving Xarelto include:

• Active pathological bleeding
• Severe hypersensitivity reaction to Xarelto

Adverse Reactions

The most common adverse reaction (>5%) was bleeding.

Risks for Specific Populations

Certain individuals may face additional or increased risks when using prescription drugs. Risks of Xarelto for specific populations include:

• Nursing mothers: discontinue drug or discontinue nursing
• Renal impairment: Avoid or adjust dose based on CrCl and Indication
• Hepatic impairment: Avoid use in patients with Child-Pugh B and C hepatic impairment or with any degree of hepatic disease associated with coagulopathy

Talk to Your Doctor Before Taking Xarelto

Before taking Xarelto, patients should tell their doctor if they:

• Have ever had bleeding problems
• Have liver or kidney problems
• Have any other medical condition
• Are pregnant or plan to become pregnant
• Are breastfeeding or plan to breastfeed

Patients should also tell their doctor about all their prescription and nonprescription drugs, medicines, vitamins, and herbal supplements. Patients should be especially aware if they take:

• Ketoconazole (Nizoral)
• Itraconazole (Onmel, Sporanox)
• Ritonavir (Norvir)
• Lopinavir/ritonavir (Kaletra)
• Indinavir (Crixivan)
• Carbamazepine (Carbatrol, Equetro, Tegretol, Tegretol-XR, Teril, Epitol)
• Phenytoin (Dilantin-125, Dilantin)
• Phenobarbital (Solfoton)
• Rifampin (Rifater, Rifamate, Rimactane, Rifadin)
• St. John’s wort (Hypericum perforatum)

Complications from Using Xarelto

Warnings and Precautions

• Xarelto can cause serious and fatal bleeding. Promptly evaluate signs and symptoms of blood loss.
• Use Xarelto with caution in pregnant women due to the potential for obstetric hemorrhage and/or emergent delivery.
• Prosthetic heart valves: Xarelto use is not recommended for patients with prosthetic heart valves.

Black Box Warning

A black box warning is the most serious and important warning on a prescription drug label. It is designed to call attention to the most serious or life-threatening risks of using a prescription drug.

The black box warning for Xarelto includes: Premature discontinuation of Xarelto increases the risk of thrombotic events; and spinal/epidural hematoma.

“Premature discontinuation of Xarelto increases the risk of thrombotic events. Premature discontinuation of any oral anticoagulant, including Xarelto, increases the risk of thrombotic events. If anticoagulation with Xarelto is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.”

“Epidural or spinal hematomas have occurred in patients treated with Xarelto who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:

• use of indwelling epidural catheters
• concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants
• a history of traumatic or repeated epidural or spinal punctures
• a history of spinal deformity or spinal surgery
• optimal timing between the administration of Xarelto and neuraxial procedures is not known.”

“Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.”

Academic Review and Clinical Studies

The Duke Clinical Research Institute was hired by Johnson & Johnson and Bayer (the companies which sell Xarelto) to conduct a three-year clinical trial. The trial involved more than 14,000 patients. However, Duke and the drug companies have since come under fire for leaving out lab data in publishing the Xarelto results.

Duke researchers published an analysis of how a faulty monitoring device impacted the clinical trial results in The New England Journal of Medicine. The authors concluded that the problems with the device did not change the trial’s results. However, the letter did not include lab data for blood samples that were taken 12 and 24 weeks after patients enrolled in the trial. Journal editors said they did not know about the lab data until a reporter for the New York Times questioned them about the data.

An analysis that included the lab data was conducted by the European Medicines Agency. A report concluded the device most likely did not affect the trial’s outcome; however, it did find the monitoring device was highly inaccurate.

Continuing Clinical Studies

According to a listing of clinical trials from the U.S. National Institutes of Health, there are currently more than 20 active studies involving Xarelto and nearly 100 recruiting studies involving Xarelto. These studies are taking place both in the U.S. and internationally. These trials include:

• Assessing the safety of Xarelto in the pre-diagnosis phase of DVT;
• Safety of Xarelto in the management of acute non-neoplastic PVT compensated cirrhosis;
• Safety of Xarelto compared to placebo in the prevention of symptomatic VTE events and VTE-related death post-hospital discharge in high-risk, medically ill patients; and
• Xarelto granules for oral suspension formulation in children.

Xarelto Warnings and Recall Notices

Faulty Monitoring Device Used in Clinical Trials

In 2016, the FDA conducted analyses to determine whether a faulty monitoring device affected the clinical trial results of Xarelto. In July 2016, a monitoring device was recalled because of the potential to generate inaccurate results. The Alere INRatio device was used to monitor warfarin therapy in the control group of the ROCKET-AF clinical trial, which provided data in support of the 2011 approval of the blood thinner drug Xarelto (rivaroxaban).

The FDA “determined that effects on strokes or bleeding, including bleeding in the head, were minimal. The FDA concludes that Xarelto is a safe and effective alternative to warfarin in patients with atrial fibrillation.”

FDA Adverse Event Reporting System (AERS)

The consumer safety group, the Institute for Safe Medication Practices (ISMP) compiles data from the FDA’s MedWatch, based on adverse events reports using the AERS system. In 2015, there were 10,674 adverse reports involving Xarelto, the highest of all drugs monitored in the US by the FDA. For comparison, the average number of reports per drug was 7.

Most of Xarelto adverse reports (8,643 or 80.9%) involved a hemorrhage, or internal bleeding. The next most common adverse report involved Xarelto failing to perform its intended purpose, resulting in 1,611 (10.9%) embolic-thrombotic or clot-related events. These adverse reports resulted in over 4,500 hospitalizations and 1,121 deaths.

Xarelto Contamination Recall

According to the FDA, Johnson & Johnson’s Janssen Ortho issued a nationwide recall of 13,500 bottles of Xarelto because of microbial contamination. The reason for the recall was “microbial contamination of non-sterile products.” The company became aware of the contamination after a consumer reported microbial contamination in a sales sample. The company recalled the lot of Xarelto manufactured by Janssen Ortho in Gurabo, Puerto Rico.

In 2016, the FDA conducted analyses to determine whether a faulty monitoring device affected the clinical trial results of Xarelto. In July 2016, a monitoring device was recalled because of the potential to generate inaccurate results. The Alere INRatio device was used to monitor warfarin therapy in the control group of the ROCKET-AF clinical trial, which provided data in support of the 2011 approval of the blood thinner drug Xarelto (rivaroxaban).

Patients Legal Rights

There are many ways that drugs and pharmaceuticals may be defective. This could include a design defect where the drug is not safe for the intended use or the drug manufacturer failed to properly warn the patient about dangers involved with taking the drug.

Patients who are injured by defective drugs may be able to seek damages from the drug company. Damages can include medical costs, income loss, and pain and suffering. Individuals who lose a loved one because of a drug defect may be able to file a wrongful death claim against the drug company.

Current Xarelto Cases

Tens of thousands of claims have been filed against Bayer Healthcare, Johnson & Johnson, and Janssen Pharmaceuticals involving Xarelto injuries and deaths. Claims include injuries related to internal bleeding and blood clots. The plaintiffs claims include that Xarelto is defective, unreasonably dangerous, and was not adequately tested for safety. Many of these cases are ongoing and others may be settled with the company for undisclosed amounts.

Xarelto Verdicts

In an early Xarelto test case, a federal jury in New Orleans found for the drug company. The plaintiff was a 75-year-old man who was prescribed Xarelto to treat a heart condition. The patient suffered gastrointestinal bleeding which resulted in hospitalization and required numerous blood transfusions. On May 3, 2017, in the first bellwether trial, the jury returned a verdict in favor of the defendants.

Xarelto Drug Defect Lawyers Gilman & Bedigian

If you were injured by after taking Xarelto or another defective drug, you may have a legal claim for medical bills, lost wages, and other damages. If a loved one died as the result of taking defective medication, you should talk to experienced drug defect attorneys about your claim. You should not have to suffer due to the drug company’s negligence.

At Gilman & Bedigian, we will use our experience, knowledge, and dedication to fight for you to receive the compensation you and your family deserve. Our aggressive trial lawyers have helped our clients recover millions of dollars in compensation for medical and defective drug injuries. Contact us online or call our law office at (800) 529-6162 for a free consultation.