Rivaroxaban

Rivaroxaban is a prescription medicine used to reduce the risk of stroke and blood clots in people with atrial fibrillation, not caused by a heart valve problem.

• Rivaroxaban is also used to treat deep vein thrombosis and pulmonary embolism, and to help reduce the risk of these conditions occurring again, and to reduce the risk of forming a blood clot in the legs and lungs of people who have just had knee or hip replacement surgery.
• Rivaroxaban is available under the following different brand names: Xarelto.

Dosages of Rivaroxaban

Adult Dosage Forms and Strengths

Tablet

• 10 mg
• 15 mg
• 20 mg

Dosage Considerations – Should be Given as Follows:

DVT Prophylaxis (Orthopedic Surgery)

• Indicated for prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing knee or hip replacement surgery
• Knee replacement: 10 mg orally once/day for 12 days; may take with or without food
• Hip replacement: 10 mg orally once/day for 35 days; may take with or without food
• Administer initial dose at least 6-10 hours after surgery once hemostasis has been established

Nonvalvular Atrial Fibrillation

• Indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation
• 20 mg/day orally with the evening meal

Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE) Treatment

• Indicated for the treatment of DVT and PE
• 15 mg orally every 12 hours for 21 days with food, THEN 20 mg orally once/day for 6 months

Reduce risk for recurrent DVT or PE

• Indicated to reduce the risk of recurrence of DVT and PE following initial 6 months treatment for DVT and/or PE
• 20 mg orally once/day following initial 6 months of treatment for DVT and/or PE

Dosage Modifications

Renal impairment (risk reduction of recurrent DVT/PE)

• Moderate (CrCl 30 to less than 50 mL/min): Observe closely and promptly evaluate any signs or symptoms of blood loss in patients with moderate renal impairment
• Severe (CrCl less than 30 mL/min): Avoid use, due to expected increase in rivaroxaban exposure and pharmacodynamic effects
• If acute renal failure develops while on rivaroxaban, discontinue treatment

Renal impairment (nonvalvular AF)

• CrCl greater than 50 mL/min: Dose adjustment not necessary
• CrCl 15-50 mL/min: 15 mg/day
• End-stage renal disease (ESRD) on intermittent renal dialysis: 15 mg/day
• Periodically assess renal function as clinically indicated (i.e., more frequently in situations in which renal function may decline) and adjust therapy accordingly; consider dose adjustment or discontinuation in patients who develop acute renal failure while on therapy

Renal impairment (postoperative thromboprophylaxis)

• CrCl greater than 50 mL/min: Dose adjustment not necessary
• CrCl 30-50 mL/min: Use with caution; dose adjustment not necessary
• CrCl less than 30 mL/min: Avoid use

Hepatic impairment

• Moderate impairment: Not studied
• Avoid use in patients with moderate-to-severe impairment (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment or with any hepatic disease associated with coagulopathy

Dosing Considerations

Discontinuation for surgery or other procedures

• Stop rivaroxaban at least 24 hours before the procedure
• Restart rivaroxaban after surgery/procedure as soon as adequate hemostasis is established
• If unable to take oral medication following surgical intervention, consider administering a parenteral drug

Switching to rivaroxaban

• From warfarin to rivaroxaban: Discontinue warfarin and start rivaroxaban as soon as INR is below 3.0
• From anticoagulant other than warfarin to rivaroxaban: Start rivaroxaban 0 to 2 hours prior to next scheduled evening administration of the drug and omit administration of the other anticoagulant
• From unfractionated heparin continuous infusion to rivaroxaban: Stop infusion and start rivaroxaban at the same time

Switching from rivaroxaban

• From rivaroxaban to warfarin: No clinical trial data are available; INR measurements made during coadministration with warfarin may not be useful for determining the appropriate dose of warfarin; one approach is to discontinue rivaroxaban and begin both a parenteral anticoagulant and warfarin at the time the next dose of rivaroxaban would have been taken
• From rivaroxaban and transitional to rapid-onset anticoagulant: Discontinue rivaroxaban and five first doses of another anticoagulant at the time the next rivaroxaban dose would have been taken

Pediatric: Safety and efficacy not established

Administration

• 10 mg tablets: May take with or without food
• 15 mg and 20 mg tablets: Take with food

Patients unable to swallow whole tablets

• 10 mg, 15 mg, or 20 mg tablets may be crushed and mixed with applesauce immediately prior to use
• After administration of a crushed 15 mg or 20 mg tablet, the dose should be immediately followed by food
• Stable in applesauce for up to 4 hours

Feeding tube administration

• 10 mg, 15 mg, or 20 mg tablets may be crushed and suspended in 50 mL of water and administered via NG or gastric feeding tube
• Absorption dependent on site of drug release in the gastrointestinal tract (gastric vs. small intestine); avoid administrating distal to the stomach which can result in reduced absorption and thereby, reduced drug exposure
• When administering as a crushed tablet via a feeding tube, confirm the gastric placement of the tube
• After administration of a crushed 15 mg or 20 mg tablet, the dose should be immediately followed by enteral feeding
• Stable in water for up to 4 hours

Missed dose

• If a dose is not taken at the scheduled time, take as soon as possible on the same day and continue on the following day with the once-daily regimen as recommended
• If taking 15 mg every 12 hours: Take immediately to ensure intake of 30 mg/day; in this instance, two 15 mg tablets may be taken at once; continue with regular 15 mg every 12 hours on the following day
• If taking 10, 15, or 20 mg once/day: Take the missed dose immediately

Common side effects of rivaroxaban include:

• Abdominal pain
• Back pain
• Blister
• Bleeding
• Atrial fibrillation (21%; major bleeding 6%)
• DVT prophylaxis (5-6%; major bleeding <1%)
• DVT treatment (6-10%; major bleeding 1%)
• Hematoma (<3%)
• Blood in the urine
• Bruising
• Constipation
• Diarrhea
• Dizziness
• Fainting
• Fatigue
• Fever
• Headache
• Indigestion
• Itching
• Muscle pain
• Muscle spasms
• Nausea
• Nosebleed
• Osteoarthritis
• Pain in your arms or legs
• Rash
• Sore throat
• Swelling of extremities
• Toothache
• Urinary tract infection
• Vomiting
• Wound secretion

Less common side effects of rivaroxaban include:

• Agranulocytosis
• Dry mouth
• Fatal bleeding
• Heavy or prolonged menstrual periods
• Hemorrhage
• Hepatitis
• Hives
• Increased amylase
• Increased BUN
• Low blood platelets (thrombocytopenia)
• Low blood pressure (hypotension)
• Painful or difficult urination
• Retroperitoneal bleeding
• Stevens-Johnson syndrome
• Weakness of one side of the body
• Yellowing skin and eyes (jaundice)

This is not a complete list of side effects and other serious side effects may occur. Call your doctor for information and medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

If your doctor has directed you to use this medication for your condition, your doctor or pharmacist may already be aware of any possible drug interactions or side effects and may be monitoring you for them. Do not start, stop, or change the dosage of this medicine or any medicine before getting further information from your doctor, healthcare provider, or pharmacist first.

• Severe interactions of rivaroxaban include:
  • defibrotide
  • prothrombin complex concentrate, human
• Serious interactions of rivaroxaban include:
  • apixaban
  • clarithromycin
  • cobicistat
  • conivaptan
  • edoxaban
  • factor X, human
  • idelalisib
  • indinavir
  • ketoconazole
  • ritonavir
• Rivaroxaban has moderate interactions with at least 90 different drugs.
• Rivaroxaban has no known mild interactions with other drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

Epidural or spinal hematomas

• May occur in patients who are anticoagulated and are receiving neuraxial anesthesia or undergoing spinal puncture; consider the benefits and risks in anticoagulated patients who are candidates for neuraxial intervention; optimal timing between therapy administration and neuraxial procedures is not known
• These hematomas may result in long-term or permanent paralysis; consider these risks when scheduling patients for spinal procedures
• Factors increasing risk: Indwelling epidural catheters, coadministration with other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants, history of traumatic or repeated epidural or spinal punctures, history of spinal deformity or spinal surgery
• Monitor patients frequently for signs and symptoms of neurologic impairment; if a neurologic compromise is noted, urgent treatment is necessary
• Epidural catheters should not be removed earlier than 18 hours after the last administration of rivaroxaban; the next dose is not to be administered earlier than 6 hours after the removal of the catheter; if a traumatic puncture occurs, delay rivaroxaban administration for 24 hours
• Discontinuing use for atrial fibrillation
• Premature discontinuation of anticoagulants, including rivaroxaban, places patients at increased risk for thrombotic events
• If anticoagulation with rivaroxaban must be discontinued for a reason other than pathologic bleeding, consider administering another anticoagulant

This medication contains rivaroxaban. Do not take Xarelto if you are allergic to rivaroxaban or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Hypersensitivity
• Active, major bleeding

Effects of Drug Abuse

• No information available

Short-Term Effects

• See "What Are Side Effects Associated with Using Rivaroxaban?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Rivaroxaban?"

Cautions

• Neuraxial anesthesia.
• The risk for thrombotic events increased with premature discontinuation.
• Safety and efficacy not established in patients with prosthetic heart valves.
• Increases risk of bleeding and can cause serious and fatal bleeding; reports of major hemorrhages, including epidural hematomas, adrenal bleeding, and intracranial, gastrointestinal, and retinal hemorrhages; promptly evaluate signs and symptoms of blood loss and consider the need for blood replacement; discontinue active pathological hemorrhage.
• Not recommended acutely as an alternative to unfractionated heparin in patients with pulmonary embolism who present with hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy.
• An indwelling epidural or intrathecal catheter should not be removed before at least 2 half-lives have elapsed (i.e., 18 hours in young patients aged 20 to 45 years and 26 hours in elderly patients aged 60 to 76 years), after last administration; the next dose should not be administered earlier than 6 hours after removal of the catheter.
• If a traumatic puncture occurs, delay administration for 24 hours.
• Periodically assess renal function as clinically indicated (i.e., more frequently in situations in which renal function may decline) and adjust therapy accordingly; consider dose adjustment or discontinuation of therapy in patients who develop acute renal failure while on therapy.
• Use with caution in pregnant women and only if the potential benefit justifies the potential risk to the mother and fetus (see "Pregnancy and Lactation").
• Avoid in patients with moderate-to-severe hepatic impairment (Child-Pugh classes B and C) or patients with any hepatic disease associated with coagulopathy.
• Drug interaction overview
  • Avoid concomitant use of P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir/ritonavir, conivaptan)
  • Caution with concomitant use of P-GP and weak or moderate CYP3A4 inhibitors (e.g., erythromycin, azithromycin, diltiazem, verapamil, quinidine, ranolazine, dronedarone, amiodarone, felodipine, citalopram, escitalopram, fluoxetine, fluvoxamine, desvenlafaxine, venlafaxine)
  • Avoid concomitant use of P-GP and strong CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin, St. John's wort ); these drugs may decrease the systemic effects and efficacy of rivaroxaban
  • Concomitant use of other drugs that impair hemostasis increases the risk of bleeding; these include aspirin, P2Y12 platelet inhibitors, other antithrombotic agents, fibrinolytic therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors
  • Clopidogrel: Avoid concomitant use unless the benefit outweighs the bleeding risk; change in bleeding time was found to be approximate twice the maximum increase seen with either drug alone

Pregnancy and Lactation

• Use rivaroxaban with caution during pregnancy if the benefits outweigh the risks. Animal studies show risk and human studies are not available or neither animal nor human studies were done. Use rivaroxaban with caution in pregnant women and only if the potential benefit justifies the potential risk to the mother and fetus.
• Dosing in pregnancy has not been studied.
• The anticoagulant effect of rivaroxaban cannot be monitored with standard laboratory testing nor readily reversed.
• Promptly evaluate any signs or symptoms suggesting blood loss (e.g., decreased hemoglobin and/or hematocrit, hypotension, or fetal distress).
• It is unknown whether rivaroxaban is distributed in human breast milk; it is not recommended for use while breastfeeding. A decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.