Rivaroxaban (Xarelto, Roxarel, Rivoban) is a Factor Xa inhibitor that is used to treat the following conditions:

1. Treatment of DVT (deep vein thrombosis) and PE (pulmonary embolism).

2. Prevention of thromboembolism in patients with non-valvular atrial fibrillation

3. Prevention of deep vein thrombosis in patients with a total knee replacement or hip arthroplasty

4. Prevention of DVT recurrence in patients who have been treated with a full dose of anticoagulants for six months and are at risk of recurrence.

5. In patients with coronary artery disease or peripheral arterial disease.

6. Unlabeled uses of rivaroxaban include acute symptomatic superficial vein thrombosis, heparin-induced thrombocytopenia, and acute coronary syndrome after initial stabilization.

Contraindications to Rivaroxaban (Xarelto, Roxarel):

Patients with active bleeding or who have an allergy to Rivaroxaban are advised not to take Rivaroxaban. It is also contraindicated:

• Patients with advanced liver disease and synthetic dysfunction (child class A and C),
• There are several bleeding conditions that can be dangerous, such as active bleeding peptic ulcer, ischemic strike, and of-course hemorhagic stroke.
• Patients who are taking CYP3A4 inhibitors such as ketoconazole or itraconazole, ritonavir and posaconazole
• Concomitant use with another anticoagulant including heparin, warfarin, apixaban, and fondaparinux, and
• For pregnant or lactating mothers.

Warnings and precautions

• Patients at high risk of bleeding should not use rivaroxaban as it can cause bleeding. These conditions can lead to excessive bleeding in patients:
  • Bacterial endocarditis
  • Congenital bleeding or acquired bleeding diathesis
  • Low platelets count
  • Biopsy of any major organ
  • Recent puncture at uncompressible location
  • Hypertension uncontrolled
  • Intracerebral or stroke
  • Vascular retinopathy
  • Use of other anticoagulants/NSAIDs concurrently with this medication,
  • Ageing in advanced
• Patients who stop receiving treatment prematurely or for other reasons than active bleeding can suffer from strokes and thrombosis.
• Advanced renal disease patients with a creatinine clearance less than 30ml/min should avoid it. It is safe to use in patients with a creatinine clearance between 30 and 50 ml/min.
• You should avoid it or use caution if you have liver disease.
• Patients with prosthetic hearts valves should avoid it.
• The drug should be used with caution by elderly patients (greater 65 years old).
• Permanent paralysis may occur after a lumbar puncture or spinal anesthesia.

Get Special Alerts

Health Canada issued an alert regarding an increase in mortality among patients who received rivaroxaban after a transcatheter valve replacement. It is not approved for use in patients who have prosthetic heart valves.

Rivaroxaban: Drug Interaction

Risk Factor C (Monitor therapy)
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.)	May enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor.
Bosentan	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Bromperidol	May enhance the adverse/toxic effect of Anticoagulants.
Caplacizumab	May enhance the anticoagulant effect of Anticoagulants.
Collagenase (Systemic)	Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased.
Dasatinib	May enhance the anticoagulant effect of Anticoagulants.
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Deferasirox	Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased.
Deoxycholic Acid	Anticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased.
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Factor X (Human)	Anticoagulants (Inhibitors of Factor Xa) may diminish the therapeutic effect of Factor X (Human).
Fat Emulsion (Fish Oil Based)	May enhance the anticoagulant effect of Anticoagulants.
Ibritumomab Tiuxetan	Anticoagulants may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding.
Ibrutinib	May enhance the adverse/toxic effect of Anticoagulants.
Inotersen	May enhance the anticoagulant effect of Anticoagulants.
Ivosidenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Limaprost	May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased.
Nevirapine	May decrease the serum concentration of Rivaroxaban.
Nintedani	Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased.
Nonsteroidal Anti-Inflammatory Agents	May enhance the anticoagulant effect of Anticoagulants.
Obinutuzumab	Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.
Omega-3 Fatty Acids	May enhance the anticoagulant effect of Anticoagulants.
Oritavancin	May diminish the therapeutic effect of Anticoagulants. Specifically, oritavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses.
Oxcarbazepine	May decrease the serum concentration of Rivaroxaban.
Pentosan Polysulfate Sodium	May enhance the anticoagulant effect of Anticoagulants.
Prostacyclin Analogues	May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination.
Salicylates	May enhance the anticoagulant effect of Anticoagulants.
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Sugammadex	May enhance the anticoagulant effect of Anticoagulants.
Sulodexide	May enhance the anticoagulant effect of Anticoagulants.
Telavancin	May diminish the therapeutic effect of Anticoagulants. Specifically, telavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses.
Thrombolytic Agents	May enhance the anticoagulant effect of Anticoagulants. Management: See full drug monograph for guidelines for the use of alteplase for acute ischemic stroke during treatment with oral anticoagulants.
Tibolone	May enhance the anticoagulant effect of Anticoagulants.
Tipranavir	May enhance the anticoagulant effect of Anticoagulants.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Vitamin E (Systemic)	May enhance the anticoagulant effect of Anticoagulants.
Vitamin K Antagonists (eg, warfarin)	Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists.
Risk Factor D (Consider therapy modification)
Antiplatelet Agents (P2Y12 Inhibitors)	May enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor.
Aspirin	May enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely.
Clarithromycin	May increase the serum concentration of Rivaroxaban. Management: In patients with impaired renal function, clarithromycin should not be used unless the potential benefits outweigh the potential risks. This interaction is unlikely clinically significant in patients with normal renal function.
Dabrafenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
Erythromycin (Systemic)	May increase the serum concentration of Rivaroxaban. Management: In patients with impaired renal function, erythromycin should not be used unless the potential benefits outweigh the potential risks. This interaction is unlikely clinically significant in patients with normal renal function.
Estrogen Derivatives	May diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of estrogens against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Exceptions: Tibolone.
Fusidic Acid (Systemic)	May increase the serum concentration of Rivaroxaban. Management: Consider alternatives to this combination when possible. Rivaroxaban dose adjustments may be required when used with systemic fusidic acid. Patients using this combination should be monitored extra closely.
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry)	May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Management: Avoid such combinations when possible. If used concomitantly, increase diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds).
Inhibitors of CYP3A4 (Moderate) and P-glycoprotein	May increase the serum concentration of Rivaroxaban. Management: No action is needed in patients with normal renal function. US labeling recommends avoidance in patients with estimated creatinine clearance 15 to 80 mL/min unless prospective benefits outweigh the risks. Other non-US labels may differ.
Lorlatinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.
Nonsteroidal Anti-Inflammatory Agents (Nonselective)	May enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of rivaroxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding.
Progestins	May diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of progestins against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations.
Risk Factor X (Avoid combination)
Anticoagulants	May enhance the anticoagulant effect of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Exceptions: Acenocoumarol; Warfarin.
Apixaban	May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods.
Cobicistat	May increase the serum concentration of Rivaroxaban.
CYP3A4 Inducers (Strong)	May decrease the serum concentration of Rivaroxaban.
Dabigatran Etexilate	May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods.
Edoxaban	May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment.
Hemin	May enhance the anticoagulant effect of Anticoagulants.
Inhibitors of CYP3A4 (Strong) and P-glycoprotein	May increase the serum concentration of Rivaroxaban. Exceptions: Clarithromycin.
MiFEPRIStone	May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of bleeding may be increased.
Omacetaxine	Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL.
St John's Wort	May decrease the serum concentration of Rivaroxaban.
Urokinase	May enhance the anticoagulant effect of Anticoagulants.
Vorapaxar	May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding.

Rivaroxaban (Xarelto, Roxarel) dose in Adults:

1. For the treatment of venous thromboembolism (deep vein thrombosis/ Pulmonary embolism):

   • Oral tablets 15 mg twice daily for 21 days followed by 20 mg once daily
     • For a total of three months in patients with provoked DVT
     • For six months in patients with unprovoked DVT

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2. For the prevention of DVT recurrence in high-risk patients:

   • Oral tablets 10 mg once daily. Patients should be reassessed at periodic intervals

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3. For the prophylaxis of venous thromboembolism (patients undergoing total knee replacement or hip arthroplasty)

   • Oral tablets 10 mg initiated 6 to 10 hours after surgery for a total of 10 to 14 days (maybe extended to 35 days in patients at high risk like those undergoing total hip arthroplasty.

     ---

4. Non-valvular atrial fibrillation to prevent systemic embolization:

   • Oral 20 mg once daily with the evening meal
   • Oral 15 mg with concomitant antiplatelets in patients with non-valvular atrial fibrillation and post-percutaneous intervention with the placement of a stent

     ---

5. Stable coronary artery disease or peripheral arterial disease:

   • Oral 2.5 mg twice daily with low dose aspirin

     ---

6. Acute coronary syndrome after the initial stabilization:

   • Oral 2.5 mg twice daily with low dose aspirin and clopidogrel for one year in patients at low risk of bleeding.

     ---

7. Heparin-induced thrombocytopenia(HIT):

   • HIT with thrombosis:

     • Oral 15 mg twice daily for 21 days followed by 20 mg once daily with food for a minimum of three months

   • HIT without thrombosis:

     • Oral 15 mg twice daily with food until recovery of platelets or for 21 days followed by 20 mg once daily for a minimum of four weeks.

       ---

8. Acute symptomatic superficial vein thrombosis:

   • Patients with recurrent superficial vein thrombosis and those at high risk of thromboembolism may be treated with rivaroxaban 10 mg once daily for 45 days.

     ---

9. Transitioning between anticoagulants:

   • The transition from LMWH or Fondaparinux:

     • Start Rivaroxaban within two hours prior to the next scheduled dose.
     • It may also be given within 6 to 12 hours after the last dose in patients on twice-daily LMWH

   • The transition from Heparin, bivalirudin, and argatroban infusion:

     • Start rivaroxaban after the infusion is stopped

   • The transition from Warfarin:

     • Start rivaroxaban when the INR is close to 2 (or when it falls to less than 2.5)

   • The transition from rivaroxaban to LMWH, unfractionated Heparin or fondaparinux:

     • Start parenteral therapy at the time of the next scheduled dose of rivaroxaban

   • The transition from Rivaroxaban to Warfarin:

     • Give warfarin for two days and then discontinue rivaroxaban
     • Alternatively, Stop rivaroxaban, initiate parenteral therapy with heparin along with warfarin and then discontinue the parenteral therapy once INR is achieved

   • The transition between other direct oral anticoagulants:

     • Start the drug at the time of the next scheduled dose.

Rivaroxaban (Xarelto, Roxarel) renal dose adjustment:

• Patients with the acute coronary syndrome and creatinine clearance of less than 30 ml/min:

  • Avoid its use

    ---

• Stable coronary artery disease or peripheral arterial disease:

  • Creatinine clearance > 15 ml/min:

    • No adjustment in the dose required

  • Creatinine clearance < 15 ml/min:

    • Avoid or use with extreme caution

      ---

•  Nonvalvular atrial fibrillation:

  • CrCl greater than 50 ml/min:

    • No adjustment in the dose required

  • CrCl 15-50 ml/min:

    • 15 mg once daily with food

  • CrCl < 15 ml/min:

    • Avoid or use with extreme caution

      ---

• Percutaneous intervention with stent placement and nonvalvular atrial fibrillation:

  • CrCl greater than 50 ml/min:

    • No adjustment in the dose required

  • CrCl 30-50 ml/min:

    • 10 mg once daily with food

  • CrCl < 30 ml/min:

    • Avoid or use with extreme caution

      ---

• Deep vein thrombosis and pulmonary embolism/ indefinite anticoagulation:

  • CrCl greater than 30 ml/min:

    • No adjustment in the dose required

  • CrCl < 30 ml/min:

    • • Avoid its use

        ---

• For prophylaxis of venous thromboembolism in patients with TKR or THA:

  • CrCl greater than 50 ml/min:

    • No adjustment in the dose required

  • CrCl 30-50 ml/min:

    • Use with caution

  • CrCl < 30 ml/min:

    • Avoid its use

      ---

• ESRD on hemodialysis:

  • No adjustment in dose mentioned in the manufacturer's labeling

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Rivaroxaban (Xarelto, Roxarel) dose in liver disease:

• Patients with mild hepatic impairment (Child class A):

  • No dose adjustment required

• Patients with Moderate to severe liver disease (Child Class B or C):

  • Avoid its use.

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Xarelto dose in elderly patients:

Elderly patients with a CrCl of less than 50 ml/min: Reduce the dose

Elderly patients with a CrCl of less than 30 ml/min: Avoid it use

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Xarelto dose in obese individuals:

Avoid its use in patients who weigh more than 120 kgs and those with a BMI of greater than 40 kg/m²

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How to administer rivaroxaban (Xarelto, Roxarel):

• Patients should be advised to take the drug with meals. doses of less than 10 mg may be taken without regard to meals.
• Patients who can not take the tablet as a whole and those on nasogastric feeding may crush the tablet and take it with 50 ml of water.
• Patients taking the drug for the prevention of thromboembolism should take the drug in the evening.

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Rivaroxaban in pregnancy and breastfeeding:

It can cause bleeding in the fetus and enters the placenta. It is not recommended to be used during pregnancy. Breastfeeding mothers should be aware that it can be dangerous.

How to monitor?

Routine monitoring of the coagulation tests is not required.

Blood CP with differential counts, liver function tests, and renal function tests may be advised before the start of therapy and when indicated during the treatment.

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Side effects of rivaroxaban (Xarelto, roxarel):

• Bleeding,
• dizziness,
• insomnia,
• anxiety,
• depression,
• fatigue,
• pruritis,
• blister formation,
• abdominal pain,
• skeletal and muscular pains,
• hepatotoxicity,
• pulmonary hemorrhage,
• bronchiectasis,
• anaphylaxis,
• thrombocytopenia,
• DRESS syndrome,
• Steven-Johnson syndrome,
• spinal,
• retroperitoneal and
• cerebral hemorrhage.

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How to manage the patient if the patient bleeds while on rivaroxaban?

• Depending upon the severity of bleeding, gastric lavage with activated charcoal may be used if the ingestion occurred within two hours.
• Andexanet alfa may be used to promptly reverse the action of rivaroxaban in patients with life-threatening bleeding.
• Hemodialysis, vitamin K, and Protamine sulfate do not affect the activity of rivaroxaban.
• Where andexanet is not available, prothrombin concentrate may be used.

Rivaroxaban MOA (Mechanism of action):

• It directly blocks Factor Xa and reversibly affects both the coagulation pathways.
• Increased food intake increases bioavailability. Rapid absorption

The time it takes to reach peak plasma levels is between 2 and 4 hours

The half-life of an individual is between 5 and 9 hours.

It is extended by 3 to 5 hours for the elderly.

Metabolism occurs via the liver while excretion is done via the urine.

International Brands of Rivaroxaban:

Price of Rivaroxaban (Xarelto) in the US:

Tablet Therapy Pack (Xarelto Starter Pack Oral)

• 15 & 20 mg (per each): $17.92

Tablets (Xarelto Oral)

• 2.5 mg (per each): $8.96
• 10 mg (per each): $17.92
• 15 mg (per each): $17.92
• 20 mg (per each): $17.92

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Rivaroxaban Brand Names (International):

• Ksarelto;
• Orgoroxaban;
• Rivarox;
• RivaXa;
• Roxarel;
• Vaxato;
• Xarelto

Rivaroxaban Brand names in Pakistan:

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Arixa (Scilife)

10 mg (10 tablets): Rs. 300

15 mg (14 tablets): Rs. 560

20 mg (14 tablets): Rs. 700

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Rivoban (Atco)

10 mg (10 tablets): Rs. 308.74

15 mg (10 tablets): Rs. 389.4

20 mg (10 tablets): Rs. 490.58

2.5 mg (14 tablets): Rs. 109.4

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Ribax (Genix)

10 mg (10 tablets): Rs. 180

15 mg (14 tablets): Rs. 350

20 mg (14 tablets): Rs. 430

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Rivaban (Paramount)

10 mg (10 tablets): Rs. 502.3

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Rivarox (AGP)

10 mg (10 tablets): Rs. 300

15 mg (14 tablets): Rs. 560

20 mg (14 tablets): Rs. 700

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Rivaxo (Getz)

10 mg (10 tablets): Rs. 290

15 mg (10 tablets): Rs. 390

20 mg (10 tablets): Rs. 490

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Roban (English pharma)

20 mg (10 tablets): Rs. 837.2

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Rayban (Ace life sciences)

10 mg (10 tablets): Rs. 280

15 mg (14 tablets): Rs. 550

20 mg (14 tablets): Rs. 650

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Xalia (CCL)

10 mg (10 tablets): Rs. 300

15 mg (10 tablets): Rs. 400

20 mg (10 tablets): Rs. 500

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Xarelto (Bayer Health care)

10 mg (5 tablets): Rs. 1525

15 mg (14 tablets): Rs. 4270

20 mg (14 tablets): Rs. 4270

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Xaroban (Searle)

10 mg (10 tablets): Rs. 300

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Xcept (Pharmevo PVT Ltd)

10 mg (10 tablets): Rs. 300

15 mg (14 tablets): Rs. 560

20 mg (14 tablets): Rs. 700

2.5 mg (10 tablets): Rs. 200