Xarelto (rivaroxaban) is a prescription medicine that is is used to treat and prevent the formation of abnormal blood clots. It is described as a “next generation” blood thinner and belongs to a class of medications called factor Xa inhibitors, which works by affecting the action of the enzyme Factor X.

Prescription Name and Overview

Xarelto comes in 2.5 mg, 10 mg, 15 mg, or 20 mg tablets. This drug is taken orally. For first time prescriptions, it is usually taken twice a day for the first three weeks, and then once a day for the succeeding days. For medication of blood clots (DVT) after a knee or hip replacement surgery, the drug is usually taken once a day. For medication for prevention of strokes and blood clots due to nonvalvular atrial fibrillation (irregular heartbeat), it is usually advised to be taken once a day after an evening meal. To prevent the recurrence of blood clots, this drug is usually taken once a day. 

It is important to follow your doctor’s advice on when and how you take the drug. Do not increase or decrease the dose on your own. Most importantly, do not stop taking the drug without your doctor’s permission.

Generic Name and Overview

Rivaroxaban is the generic name of Xarelto. However, there is no generic form of Rivaroxaban available in the United States. 

OTC  Name and Overview

Manufacturer

Xarelto was first approved by the Food and Drug Administration (FDA) in November 2011 to reduce the risk of stroke and Systemic Embolism in people with non-valvular atrial fibrillation. A year later, on November 2012, it was also approved to treat Deep Vein Thrombosis (DVT) and prevent Pulmonary Embolism (PE) in people having hip or knee replacement surgery. 

The FDA has approved Janssen Pharmaceuticals to manufacture Xarelto. By 2016, doctors had written more than 13 million Xarelto prescriptions in the United States. It has become the most prescribed blood thinner in its class in the US. 

Labeled Indications

• Reduction of the Risk of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation
• Treatment of Deep Vein Thrombosis
• Treatment of Pulmonary Embolism
• Reduction of the Risk of Recurrence of Deep Vein Thrombosis And/Or Pulmonary Embolism
• Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery
• Reduction of Risk of Major Cardiovascular Events in Patients with Chronic Coronary Artery Disease (CAD) or Peripheral Artery Disease (PAD)

Active Ingredients

Rivaroxaban is the active ingredient in Xarelto tablets.

What Is It Used For?

How Does it Work?

Xarelto is a prescription drug that works as a blood thinner by targeting the Factor Xa, affecting the formation of blood clots in a person’s arteries or veins. Factor Xa is the active form of Factor X, an enzyme that helps in the clotting of blood. 

This process depends on Vitamin K for it to work. Like other blood thinners, Xarelto is considered as a selective coagulant because it only interferes with Factor Xa, and therefore doesn’t affect so much of the body’s functions. 

Although Xarelto is called as a “blood thinner”, it doesn’t actually thin a person’s blood. It cannot dissolve the clots that are already formed in the body. What it does is reduce and prevent blood from abnormal clotting and help in preventing existing clots from growing. 

What are the Approved Uses?

Xarelto was first approved by the FDA in 2011 to be used as treatment for Deep Vein Thrombosis (DVT) and prevention of Pulmonary Embolism. DVT and PE happens when blood clots form in veins deep inside the body, usually after a hip or knee replacement surgery. 

Later that year, the FDA also approved Xarelto as a medication for people who have nonvalvular atrial fibrillation (afib). This condition increases a person’s likelihood for clots and stroke. 

In November 2012, the FDA added the use of Xarelto to include the prevention of recurrent DVT and PE. It can be taken continuously by a patient who has a high likelihood of forming abnormal blood clots.

Also that same year, Xarelto was allowed to be tested in a Phase 3 clinical trial for patients who have ACS or Acute Coronary Syndrome. The patients were given low doses of the drug twice a day as part of their treatment. The New England Journal of Medicine published the results of the study and concluded that the drug is effective for the patients. However, the FDA voted against the conclusion of the study and restricted the use of Xarelto for patients with ACS. 

In 2014, the committee once again voted against the use of Xarelto for patients with ACS as the risk of bleeding outweighed the benefits they would get from the drug.

Production Anecdotes / History

Xarelto was first approved for production on July 1, 2011 through Jannssen Pharmaceuticals. They first manufactured it in 10 mg strengths.

On November 4, 2011, the production of  15 mg and 20 mg tablets were approved. On October 11, 2018, the 2.5 mg tablets were approved for production. 

In May 7, 2018, the FDA has approved Portola Pharmaceutical’s Adexxa, the first ever antidote for factor Xa inhibitors like Xarelto and Eliquis, to reverse the effects of the drugs when bleeding becomes life threatening or uncontrollable. 

Precautions

Before taking Xarelto (rivaroxaban),

• tell your doctor and pharmacist if you are allergic to rivaroxaban, any other medications, or any of the ingredients in rivaroxaban tablets. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: amiodarone ( Pacerone), azithromycin (Zithromax), carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, Tegretol-XR, Teril), clarithromycin (Biaxin, in Prevpac), conivaptan (Vaprisol), diltiazem (Cardizem, Dilacor, Tiazac), dronedarone (Multaq), erythromycin (E.E.S., E-Mycin, Erythrocin), felodipine (Plendil), fluconazole (Diflucan), indinavir (Crixivan), itraconazole (Onmel, Sporanox), ketoconazole (Nizoral), lopinavir (in Kaletra), phenobarbital , phenytoin (Dilantin, Phenytek), quinidine, ranolazine (Ranexa), rifampin (Rifadin, in Rifamate, in Rifater, Rimactane), ritonavir (Norvir, in Kaletra), and verapamil (Calan, Verelan, in Tarka). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John’s wort.
• tell your doctor if you have heavy bleeding anywhere in your body that cannot be stopped. Your doctor will probably tell you not to take rivaroxaban.
• tell your doctor if you have had a valve in your heart replaced or have or have ever had problems with unusual bleeding, a bleeding disorder, or kidney or liver disease.
• Tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking rivaroxaban, call your doctor.
• If you are having surgery, including dental surgery, tell the doctor or dentist that you are taking rivaroxaban. (source: medlineplus.gov)

Long-Term Use Considerations

Xarelto is a long-term solution to lower a patient’s risk of experiencing stroke due to atrial fibrillation (AF). However, abruptly stopping the use of Xarelto without an alternative blood thinner, increases a patient’s risk of stroke and other thrombotic events.

Xarelto increases the risk of serious and fatal bleeding. You need to have your blood checked regularly when you’re taking the drug. Your doctor will ask you to get your “prothrombin time” or the time it takes for your blood to clot.

Drug Interactions

Drug interactions happen when a substance that you are taking changes or disrupts how a certain medication works. Interactions may be harmful to you and increase your risk for serious side effects or inhibit a drug from functioning properly. Always consult your doctor if you are going to start a medication with a new drug. 

Can Interact with the Following

Xarelto can interact negatively with the following:

• Nizoral (ketoconazole)- antifungal medication
• Onmel, Sporanox (itraconazole)- used to treat fungus or yeast infections
• Norvir (ritonavir)- HIV treatment prescription
• Kaletra (lopinavir/ritonavir)- antiretroviral fixed dose combination drug used to treat and prevent HIV/AIDS
• Crixivan (indinavir)- HIV treatment prescription
• Carbatrol, Equetro, Tegretol, Tegretol-XR,Teril, Epitol (carbamazepine)- anticonvulsant medication for treatment of seizures and nerve pain as well as bipolar disorder
• Dilantin-125, Dilantin (phenytoin)- for treatment of seizures
• Solfoton (phenobarbital)- for treatment of seizures and long-term epilepsy control
• Rifater, Rifamate, Rimactane, Rifadin (rifampin)- for treatment of tuberculosis (TB)
• St. John’s wort (Hypericum perforatum)- herbal supplement used for treatment of several health conditions

Can’t Interact with the Following

Xarelto can’t be taken with over-the-counter medicines such as painkillers, aspirin, NSAIDs, and other anticoagulants. Doing so may increase a patient’s risk of bleeding. 

Xarelto is contraindicated for use by patients with active bleeding conditions or severe allergy to rivaroxaban or any of the inactive ingredients.

When To Stop Taking

Don’t stop taking this medication abruptly without advice from your doctor. Continue taking Xarelto even if you feel well. Don’t miss any doses. 

You may need to stop taking this drug due to a surgery or dental procedure. Inform your doctor or dentist about this and ask your doctor for a substitute or how to go about the medication properly.

Long-Term Side Effects

Xarelto is a blood thinner and anticoagulant. Therefore it prevents the normal process of our blood to clot. If you experience cuts or wounds, it is normal for the clotting to take longer than usual and you may bruise or bleed more easily. 

If you notice that your bleeding or bruising is unusual, don’t hesitate to call your doctor. 

If you stop taking Xarelto, you are highly at risk for stroke. Don’t stop taking the drug without your doctor’s advice. 

FDA Warnings (History Of)

In 2013, the FDA issued a black box warning that raised the concern to patients about premature or abrupt discontinuation of the drug, as it increased the risk of stroke and spinal or epidural hematoma.

In 2014, the FDA once again required a boxed warning about the drug causing uncontrollable internal bleeding. 

In May 7, 2018, the FDA has approved Portola Pharmaceutical’s Adexxa, the first ever antidote for factor Xa inhibitors like Xarelto and Eliquis, to reverse the effects of the drugs when bleeding becomes life threatening or uncontrollable. 

Other Common Side Effects

If you experience severe muscle spasms that won’t go away, inform your doctor right away.

Other side effects may be serious. If you experience any of the following side effects, inform your doctor immediately:

• Bloody, black, or tarry stools
• Pink or brown urine
• Coughing up or vomiting material that looks like coffee grounds
• Coughing up or vomiting blood
• Frequent nosebleeds
• Gum bleeding
• Heavy menstrual bleeding
• Weakness and fatigue
• Headache
• Dizziness or fainting
• Blurred vision
• Unexplained pain in the arm or leg
• Rash
• Itching
• Difficulty breathing or swallowing
• Hives
• Pain or swelling around wounds
• Back pain
• Wound secretion
• Pruritus
• Abdominal pain
• Blister

Lawsuits

Some individuals who have used Xarelto and who claimed to have suffered from internal bleeding, wound leakage and infections after using the drug have filed lawsuits against Johnson & Johnson, Janssen Pharmaceuticals and Bayer Corporation. The drug manufacturers have won three cases so far. 

More than 25,000 federal lawsuits have been filed against Xarelto’s manufacturers and all have ended in their victory. In at least once case, the judge denied a plaintiff’s appeal for another hearing. More than 22,000 lawsuits are still pending in a Louisiana federal court.

One woman named Lynn Hartman, 75, filed a petition against Xarelto, alleging that the drug caused her to suffer from gastrointestinal bleeding after using the drug for a year to treat her irregular heartbeat. The jury in Philadelphia ordered Xarelto to pay $27.8 million to the woman. The judge later on overturned the verdict, stating that the ruling was based on a narrow issue relating to the patient’s doctor. 

Johnson & Johnson, Janssen Pharmaceuticals and Bayer Corporation deny the claims that they did not warn about the side effects of the drug, causing the patients to bleed. In court documents, the lawyers defending Xarelto’s manufacturers note that they have mentioned the risk of bleeding at least 70 times as a side effect of the drug. 

Litigations are still going on and there are still no settlements announced up to now.