What is Xarelto? (Rivaroxaban)

Rivaroxaban is used to prevent blood clots from forming due to a certain irregular heartbeat (atrial fibrillation) or after hip or knee replacement surgery. It is also used to treat blood clots (such as in deep vein thrombosis-DVT or pulmonary embolus-PE) and to prevent the blood clots from forming again.

Rivaroxaban is an anticoagulant that works by blocking certain clotting proteins in your blood.

How to use Xarelto

Read the Medication Guide provided by your pharmacist before you start taking rivaroxaban and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth as directed by your doctor. If you are taking this medication to prevent blood clots after knee or hip replacement surgery, the dose is usually taken once a day. If you are taking this drug to prevent strokes and blood clotsthat may form due to an irregular heartbeat, the dose is usually taken once a day with the evening meal. If you are taking rivaroxaban to treat blood clots, the dose is usually taken twice a day for the first 3 weeks, and then once a day. Carefully follow your doctor’s directions. Do not increase your dose, take it more often, or stop taking it unless you are told to do so by your doctor.

The 10 milligrams tablet may be taken with or without food. The 15 milligrams and 20 milligrams tablet should be taken with food. If you have any questions about how to take rivaroxaban, ask your doctor or pharmacist.

If you are unable to swallow whole tablets, you may crush the tablet and mix it with applesauce. Eat the entire mixture right away. Do not prepare a supply for future use.

If you are giving this medication through a tube into the stomach (nasogastric or gastric tube), ask your health care professional for detailed instructions on how to properly mix and give it.

The dosage and length of treatment is based on your medical condition and response to treatment.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day.

Who should NOT take this medication?

Do not take rivaroxaban if you:

• are allergic to rivaroxaban or any ingredients of the medication
• are bleeding actively or have a high risk of bleeds
• are pregnant or breast-feeding
• are taking certain medications such as ketoconazole, itraconazole, voriconazole, posaconazole, or ritonavir
• are taking other anticoagulants (blood thinners, e.g., warfarin, heparin, low molecular weight heparin, apixaban)
• have a body lesion at risk of bleeding, including bleeding in the brain within the last 6 months, or bleeding in your stomach or gut
• have liver disease associated with an increased risk of bleeding

side effects 

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• bleeding
• bruising
• constipation
• decreased energy
• diarrhea
• fluid buildup in legs, ankles
• headache
• increased menstrual bleeding
• nausea
• stomach ache
• vomiting

Although most of these side effects listed below don’t happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• bleeding or oozing from the surgical wound
• confusion
• decreased urine production
• fast heartbeat
• itchy skin or skin rash
• signs of anemia (low red blood cells; e.g., dizziness, pale skin, unusual tiredness or weakness, shortness of breath)
• signs of bleeding (e.g., bloody nose that lasts for more than 5 minutes, blood in urine, coughing blood, cuts that don’t stop bleeding, gums that bleed for longer than 5 minutes when brushing teeth, bleeding into the rectum or from hemorrhoids, excessive menstrual bleeding)
• signs of infection (symptoms may include fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness)
• signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
• signs of low blood pressure (e.g., dizziness, lightheadedness, fainting)
• stiff, sore, hot, or painful joints
• symptoms of unidentified bleeding (e.g., weakness, paleness, dizziness, headache, unexplained swelling)
• unexpected bruising or bleeding after surgery

Stop taking the medication and seek immediate medical attention if any of the following occur:

• signs of bleeding in the stomach (e.g., bloody, black, or tarry stools, spitting up of blood, vomiting blood or material that looks like coffee grounds)
• signs of a serious allergic reaction (i.e., hives, difficulty breathing, or swelling of the face and throat)
• signs of severe skin reactions (e.g., blistering, peeling, a rash covering a large area of the body, a rash that spreads quickly, or a rash combined with fever or discomfort).

warnings 

Increased bleeding risk: If you have conditions that are associated with an increased risk of bleeding (e.g., bleeding problems; uncontrolled very high blood pressure; a problem with the blood vessels in the back of the eye called retinopathy; current or past ulcer of the stomach or intestines; or recent stroke, recent surgery of the brain, spinal column, or eye), discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Kidney disease: If you have kidney disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Lactose: This medication contains lactose. People with certain rare problems associated with lactose or galactose intolerance (e.g., Lapp lactase deficiency, glucose-galactose malabsorption) should not take this medication.

Liver disease: If you have liver disease or decreased liver function, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

If you experience symptoms of liver problems such as fatigue, feeling unwell, loss of appetite, nausea, yellowing of the skin or whites of the eyes, dark urine, pale stools, abdominal pain or swelling, and itchy skin, contact your doctor immediately.

Spinal or epidural injection or catheters: If you have a spinal or epidural catheter, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Surgery: Inform all health care professionals involved in your care that you are taking rivaroxaban. Rivaroxaban may need to be stopped temporarily before dental or surgical procedures to reduce your risk of bleeding heavily during or after the procedure.

Pregnancy: This medication should not be used during pregnancy. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding: Rivaroxaban may pass into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. This medication is not recommended to be taken while breast-feeding.

Children: The safety and effectiveness of using this medication have not been established for children less than 18 years of age.

Seniors: The side effects of this medication may be more noticeable in seniors. People who are over 65 years old should discuss with their doctor how this medication may affect them and whether any special monitoring is needed.

Before taking this medicine

You should not use Xarelto if you are allergic to rivaroxaban, or if you have:

• an artificial heart valve; or
• active or uncontrolled bleeding.

Xarelto can cause a very serious blood clot around your spinal cord if you undergo a spinal tap or receive spinal anesthesia (epidural). This type of blood clot could cause long-term paralysis, and may be more likely to occur if you have:

• you have a genetic spinal defect;
• you have a spinal catheter in place;
• you have a history of spinal surgery or repeated spinal taps;
• you have recently had a spinal tap or epidural anesthesia;
• you are taking an NSAID – Advil, Aleve, Motrin, and others; or
• you are using other medicines to treat or prevent blood clots.

Xarelto may cause you to bleed more easily, especially if you have:

• a bleeding disorder that is inherited or caused by disease;
• hemorrhagic stroke;
• uncontrolled high blood pressure;
• stomach or intestinal bleeding or ulcer; or
• if you take certain medicines such as aspirin, enoxaparin, heparin, warfarin (Coumadin, Jantoven), or clopidogrel (Plavix), or certain antidepressants.

To make sure you can safely take Xarelto, tell your doctor if you have kidney or liver disease.

It is not known whether Xarelto will harm an unborn baby. However, this medicine could cause bleeding complications during childbirth. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether rivaroxaban passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using Xarelto.

How should I take rivaroxaban?

Take Xarelto exactly as prescribed by your doctor. Xarelto is taken either once per day or two times per day, depending on the reason you are using this medication. Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not take this medicine in larger or smaller amounts or for longer than recommended. Carefully follow your doctor’s dosing instructions.

For atrial fibrillation: Take the Xarelto 15-milligram or 20-milligram tablet once per day with your evening meal.

For blood clots in your legs or lungs: Xarelto is usually taken with food 1 or 2 times per day, at the same time each day.

Xarelto dosing information

The recommended dose of Xarelto for the treatment of DVT and/or PE is 15 mg taken orally twice daily with food for the first 21 days. After this initial treatment period, the recommended dose of Xarelto is 20 mg taken orally once daily with food, at approximately the same time each day.

The recommended dose of Xarelto for reduction in the risk of recurrence of DVT or PE is 20 mg taken orally once daily with food at approximately the same time each day.

In patients taking Xarelto for prevention of deep vein thrombosis (DVT), which could result in pulmonary embolism (PE) following certain surgical procedures, the recommended daily dose is 10 milligrams taken once a day, with or without food. The initial dose should be taken at six to 10 hours after surgery once the patient has been stabilized (or body functions have returned to normal).

Treatment with Xarelto should continue in patients who are taking the drug following a hip replacement surgery for a recommended duration of 35 days. For patients undergoing knee replacement surgery, Xarelto should be continued for 12 days following surgery. A patient’s doctor will ultimately decide how long his or her patient should continue to take Xarelto following surgery.

Sometimes a patient’s doctor may ask them to stop taking Xarelto for a short time prior to certain surgeries, medical or dental procedures. The doctor will also inform the patient when it is considered safe to resume treatment with the blood thinner medication.

Overdose

It is possible to overdose on Xarelto (rivaroxaban) by consuming large amounts of the drug. If an overdose is suspected, patients are urged to seek immediate treatment as potentially life-threatening bleeding complications can occur. Due to Xarelto’s high plasma protein binding, the drug is not dialyzable, meaning dialysis cannot be used to remove the medication from the patient’s blood. Since there is currently no specific antidote available to reverse bleeding in patients taking Xarelto, activated charcoal may be used to reduce absorption of the drug.

Mild cases of overdose may not result in any symptoms. Since there is currently no easy or overall effective way to treat a Xarelto overdose that results in bleeding, treatment is likely to be largely symptomatic and supportive, minimizing complications that occur rather than preventing them.

Usual Adult Dose of Xarelto for Deep Vein Thrombosis Prophylaxis after Hip Replacement Surgery:

Prevention of venous thromboembolism in patients undergoing hip or knee replacement surgery:
10 mg orally once a day starting 6 to 10 hours after surgery.

Duration of therapy is 35 days for hip replacement surgery and 12 days for knee replacement surgery.

Usual Adult Dose for Deep Vein Thrombosis Prophylaxis after Knee Replacement Surgery:

Prevention of venous thromboembolism in patients undergoing hip or knee replacement surgery:
10 mg orally once a day starting 6 to 10 hours after surgery.

Duration of therapy is 35 days for hip replacement surgery and 12 days for knee replacement surgery.

Usual Adult Dose for Atrial Fibrillation:

Nonvalvular Atrial Fibrillation:
20 mg orally, once daily with the evening meal.

Usual Adult Dose of Xarelto for Deep Vein Thrombosis:

Treatment of DVT and PE:
Initial dose: 15 mg orally twice daily with food, for first 21 days.
Maintenance dose: 20 mg orally once daily with food, for remaining treatment.

Usual Adult Dose for Pulmonary Embolism:

Treatment of DVT and PE:
Initial dose: 15 mg orally twice daily with food, for first 21 days.
Maintenance dose: 20 mg orally once daily with food, for remaining treatment.

Usual Adult Dose for Deep Vein Thrombosis – Recurrent Event:

Reduction in the Risk of Recurrence of DVT and of PE:
20 mg orally once daily with food.

Usual Adult Dose of Xarelto for Pulmonary Embolism – Recurrent Event:

Reduction in the Risk of Recurrence of DVT and of PE:
20 mg orally once daily with food.

Dental Procedures and Xarelto

Due to concerns related to bleeding risks, it is sometimes suggested that patients discontinue the use of Xarelto prior to undergoing certain dental procedures. The European Heart Rhythm Association issued a 2015 consensus guideline (updating a prior 2013 guideline), suggesting that certain procedures, such as the extraction of one to three teeth, periodontal surgery, abscess incisions or implant positioning, do not necessarily require patients to discontinue the use of Xarelto.

A 2015 narrative review concluded that with “limited dental surgery” continuing the regular dose of Xarelto or postponing the timing of the daily dose to either follow the dental treatment or skipping one daily dose altogether, may be the most conservative and beneficial options for the patient taking Xarelto. The author of the narrative pointed out that clinical trials would need to be conducted to confirm the findings.

Another narrative issued the same year confirmed the advice offered by the first narrative author, but also addressed the need to consider other supplements or drugs the patient may be taking together with Xarelto that could increase the patient’s risk for bleeding and resultant complications.

With the inclusion of a 2013 systematic review as well, the overall recommendation was to advise patients not to take Xarelto one to three hours prior to dental treatment. All of the authors acknowledged that no clinical studies or guidelines have been published to directly address the treatment management considerations of patients taking Xarelto while undergoing various dental procedures, so any recommendations made are purely subjective.

The general consensus, according to the American Dental Association (ADA), seems to be that with the newer target-specific anticoagulant medications, no change to the treatment regimen is required for patients undergoing dental treatments. But the ADA suggested that in order to be cautious, dental practitioners should consult a patient’s physician to assess the safety for each individual patient, and that when suggesting any modification to a patient’s medication regimen prior to dental surgery, that it be done in conjunction with consultation of the patient’s primary care doctor.

Other Blood Thinners

Warfarin, marketed under the brand names Coumadin and Jantoven, has been the primary anticoagulant (blood thinner) drug available to patients since its approval. However, since 2010, the FDA has approved four new oral anticoagulant drugs, including, in order, Pradaxa (dabigatran), Xarelto (rivaroxaban), Eliquis (apixaban) and Savaysa (edoxaban).

All four of these anticoagulants work to effectively reduce a patient’s overall risk of stroke associated with atrial fibrillation (AF); but they can also cause bleeding, and only two of the blood thinner drugs (warfarin and Pradaxa) currently have antidotes available to reverse this adverse effect.

Across the board the FDA concluded that all four anticoagulants in the new generation of blood thinners are equivalent to, or more effective than, warfarin in preventing strokes. Still, the existence or lack of an antidote may be a game-changer for some patients when considering which medication to take.

Other benefits of this new wave of blood thinners over the tried-and-true warfarin include fewer interactions with food and other drugs, a more rapid onset, freedom from the need to undergo periodic blood testing, and a substantially reduced risk of bleeding into the brain resulting in hemorrhagic stroke (a type of stroke that is not caused by blood clots that go into the brain, such as those found in AF patients).

Xarelto In Certain Populations

Certain individuals considering taking Xarelto may be at an increased risk for resulting complications. These individuals can include patients who have ever had bleeding problems, patients who have liver or kidney problems, or patients with other medical conditions.

The drug’s overall safety and efficacy has not been adequately studied in pregnant women, and dosing for pregnant women has not yet been established. Women with high-risk pregnancies may be at an increased risk of bleeding and premature delivery since there is no antidote for resulting hemorrhages. In animal studies, maternal bleeding and maternal and fetal death occurred during labor and delivery at a dose of 40 milligrams/kg of Xarelto. Therefore, Xarelto should be used during pregnancy only if the potential benefit justifies the potential risk to mother and fetus.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

Some products that may interact with this drug include: mifepristone, certain antidepressants (including SSRIs such as fluoxetine, SNRIs such as desvenlafaxine/venlafaxine).

Other medications can affect the removal of rivaroxaban from your body, which may affect how rivaroxaban works. Examples include cobicistat, conivaptan, certain azole antifungals (itraconazole, ketoconazole, posaconazole), rifamycins (such as rifampin), HIV protease inhibitors (such as lopinavir, ritonavir), St. John’s wort, drugs used to treat seizures (such as carbamazepine, phenytoin, phenobarbital), among others.

Aspirin can increase the risk of bleeding when used with this medication. However, if your doctor has directed you to take low-dose aspirin for heart attack or stroke prevention (usually at dosages of 81-325 milligrams a day), you should continue taking it unless your doctor instructs you otherwise. Ask your doctor or pharmacist for more details.

What Does Xarelto Treat?

Xarelto (rivaroxaban) is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (an irregular heartbeat) by preventing the formation of blood clots. It is also used as a treatment and maintenance drug for deep vein thrombosis (DVT) (a blood clot that forms in a vein deep in the body, usually in the lower leg or thigh), which may lead to pulmonary embolism (PE) (a sudden blockage in an artery of the lung) in patients having knee or hip replacement surgery.

Nonvalvular Atrial Fibrillation

Atrial fibrillation (AF) is the most common type of arrhythmia, or irregular heartbeat. If a patient has an arrhythmia, it means there is a problem with the speed or rhythm of their heartbeat. “Nonvalvular” means AF is not caused by a heart valve problem.

The cause of AF has to do with a disorder in the heart’s electrical system. A test called an electrocardiogram (EKG) can assist in the diagnosis of AF by showing the electrical waves of a patient’s heart. Complications of the condition can include an increased risk of stroke, chest pain, heart attack or heart failure, which can lead to death. Treatment of AF may include medications and/or other procedures designed to restore the heart’s normal rhythm.

Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)

Deep vein thrombosis (DVT) is a condition in which a blood clot forms in a vein deep within the body. DVT typically occurs in the large veins in the lower legs and thighs, but it can also occur in other deep veins, such as in the arms and pelvis (also called the pelvic region located between the abdomen and the thighs). If the vein swells, it is referred to as thrombophlebitis. DVT is most common in individuals over 60. However, blood clots can occur at any age.

Blood clots, including a DVT, can affect blood flow causing changes in skin color (redness), leg pain, swelling of the leg (edema), and skin that feels warm to the touch or is tender over the affected vein.

Other serious problems can result in patients if a DVT breaks loose and travels through the bloodstream to the lung. A sudden blockage in an artery in the lung is called a pulmonary embolism (PE). PE can cause permanent damage to the affected lung, low oxygen levels in a patient’s blood and damage to other organs in the body due to a lack of oxygen supply. In instances where the clot is large or there are multiple clots present, PE can even result in death.

About 50 percent of individuals who have PE are unaware that they are affected by the potentially life-threatening condition. Symptoms can include shortness of breath, chest pain or coughing up blood. The goal of treatment is to break up any existing clots and to prevent new clots from forming.

No Antidote for Bleeding

Currently, no antidote exists for reversal of bleeding associated with the use of Xarelto (rivaroxaban). Unlike with warfarin, vitamin K is not an effective reversal agent with Xarelto. Partial reversal has been seen in healthy clinical trial volunteers after the administration of prothrombin complex concentrates (PCCs). PCC, or Factor IX complex as it’s also known, is a medicine used to treat and prevent bleeding associated with a blood-clotting disorder called hemophilia B. The use of other medications with blood-clotting factors, or procoagulant reversal agents, have not been evaluated with Xarelto.

In December 2015, the New England Journal of Medicine (NEJM) published data from a study conducted by Portola Pharmaceuticals, the makers of a proposed antidote for Xarelto. Portola was hoping to launch the drug following FDA approval in 2016. In early 2015, the FDA designated the company’s lead candidate Andexxa (andexanet alfa) “a breakthrough therapy,” meaning early evidence indicated that it was representative of a substantial improvement over existing therapies, and that it would assist in the acceleration of the development and review of other drugs for serious or life-threatening conditions.

Overdose