Drug Action
Rivaroxaban is a direct inhibitor of activated factor X (factor Xa). Cardiovascular system
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Individual generic drug information
Extracted information for Rivaroxaban only.
Rivaroxaban is a direct inhibitor of activated factor X (factor Xa). Cardiovascular system
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Prophylaxis of venous thromboembolism following knee replacement surgery ▶BY MOUTH ▶Adult: 10 mg once daily for 2 weeks, to be started 6–10 hours after surgery Prophylaxis of venous thromboembolism following hip replacement surgery ▶BY MOUTH ▶Adult: 10 mg once daily for 5 weeks, to be started 6–10 hours after surgery Treatment of deep-vein thrombosis | Treatment of pulmonary embolism ▶BY MOUTH ▶Adult: Initially 15 mg twice daily for 21 days, then maintenance 20 mg once daily, to be taken with food, for duration of treatment, consult product literature Prophylaxis of recurrent deep-vein thrombosis | Prophylaxis of recurrent pulmonary embolism ▶BY MOUTH ▶Adult: 10 mg once daily, following completion of at least 6 months of anticoagulant treatment, to be taken with food, consider 20 mg once daily in those at high risk of recurrence (such as complicated comorbidities, or previous recurrence with rivaroxaban 10 mg once daily) Prophylaxis of stroke and systemic embolism in patients with non-valvular atrial fibrillation and with at least one of the following risk factors: congestive heart failure, hypertension, previous stroke or transient ischaemic attack, age 75 years, or diabetes mellitus ▶BY MOUTH ▶Adult: 20 mg once daily, to be taken with food Prophylaxis of atherothrombotic events following an acute coronary syndrome with elevated cardiac biomarkers (in combination with aspirin alone or aspirin and clopidogrel) ▶BY MOUTH ▶Adult: 2.5 mg twice daily usual duration 12 months Prophylaxis of atherothrombotic events in patients with coronary artery disease or symptomatic peripheral artery disease at high risk of ischaemic events (in combination with aspirin) ▶BY MOUTH ▶Adult: 2.5 mg twice daily DOSE EQUIVALENCE AND CONVERSION ▶For information on changing from, or to, other anticoagulants—consult product literature.
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GENERAL CONTRA-INDICATIONS Active bleeding. antiphospholipid syndrome (increased risk of recurrent thrombotic events). malignant neoplasms at high risk of bleeding. oesophageal varices. recent brain surgery. recent gastro-intestinal ulcer. recent intracranial haemorrhage. recent ophthalmic surgery. recent spine surgery. significant risk of major bleeding. vascular aneurysm SPECIFIC CONTRA-INDICATIONS ▶When used for prophylaxis of atherothrombotic events following an acute coronary syndrome Previous stroke. transient ischaemic attack ▶When used for prophylaxis of atherothrombotic events in patients with coronary artery disease or symptomatic peripheral artery disease Previous stroke (no information available—consult product literature)
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GENERAL CAUTIONS Anaesthesia with postoperative indwelling epidural catheter (risk of paralysis—monitor neurological signs and wait at least 18 hours after rivaroxaban dose before removing catheter and do not give next dose until at least 6 hours after catheter removal). bronchiectasis. elderly. prosthetic heart valve (efficacy not established). risk of bleeding. rivaroxaban should not be used as an alternative to unfractionated heparin in pulmonary embolism in patients with haemodynamic instability, or who may receive thrombolysis or pulmonary embolectomy. severe hypertension. vascular retinopathy SPECIFIC CAUTIONS ▶When used for prophylaxis of atherothrombotic events following an acute coronary syndrome Body-weight less than 60 kg ▶When used for prophylaxis of atherothrombotic events in patients with coronary artery disease or symptomatic peripheral artery disease Body-weight less than 60 kg CAUTIONS, FURTHER INFORMATION ▶Elderly For factor Xa inhibitors, prescription potentially inappropriate (STOPP criteria): . with concurrent significant bleeding risk, such as uncontrolled severe hypertension, bleeding diathesis or recent non-trivial spontaneous bleeding (high risk of bleeding) . for first deep venous thrombosis without continuing provoking risk factors (e.g. thrombophilia) for greater than 6 months (no proven added benefit) . for first pulmonary embolus without continuing provoking risk factors for greater than 12 months (no proven added benefit) . as part of dual therapy with an antiplatelet agent in patients with stable coronary, cerebrovascular or peripheral arterial disease, without a clear indication for anticoagulant therapy (no added benefit) . if eGFR less than 15 ml/min/1.73 m2 (risk of bleeding) See also Prescribing in the elderly p. 33.
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Low-dose rivaroxaban, in combination with aspirin alone or aspirin and clopidogrel, is licensed for the prevention of atherothrombotic events following an acute coronary syndrome with elevated cardiac biomarkers. Treatment should be started as soon as possible after the patient has been stabilised following the acute coronary event, at the earliest 24 hours after admission to hospital, and at the time when parenteral anticoagulation therapy would normally be discontinued; the usual duration of treatment is 12 months.
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NICE decisions ▶Rivaroxaban for the prevention of venous thromboembolism after total hip or total knee replacement in adults (April 2009) NICE TA170 Rivaroxaban (Xarelto ®) is an option for the prophylaxis of venous thromboembolism in adults after total hip replacement or total knee replacement surgery. www.nice.org.uk/guidance/ta170 ▶Rivaroxaban for the prevention of stroke and systemic embolism in people with atrial fibrillation (May 2012) NICE TA256 Rivaroxaban (Xarelto ®) is an option for the prevention of stroke and systemic embolism (in accordance with its licensed indication) in patients with non-valvular atrial fibrillation and with at least one of the following risk factors: . previous stroke or transient ischaemic attack . congestive heart failure . age 75 years . diabetes mellitus . hypertension The risks and benefits of rivaroxaban compared with warfarin should be discussed with the patient. www.nice.org.uk/guidance/ta256 ▶Rivaroxaban for the treatment of deep-vein thrombosis and prevention of recurrent deep-vein thrombosis and pulmonary embolism (July 2012) NICE TA261 Rivaroxaban (Xarelto ®) is an option for the treatment of deep-vein thrombosis and prevention of recurrent deep- vein thrombosis and pulmonary embolism in adults after diagnosis of acute deep-vein thrombosis. www.nice.org.uk/guidance/ta261 ▶Rivaroxaban for treating pulmonary embolism and preventing recurrent venous thromboembolism (June 2013) NICE TA287 Rivaroxaban (Xarelto ®) is an option for treating pulmonary embolism and preventing recurrent deep-vein thrombosis and pulmonary embolism in adults. www.nice.org.uk/guidance/ta287 ▶Rivaroxaban for preventing adverse outcomes after acute management of acute coronary syndrome (March 2015) NICE TA335 Rivaroxaban (Xarelto ®) is an option within its marketing authorisation, in combination with aspirin plus clopidogrel or aspirin alone, for preventing atherothrombotic events in patients who have had an acute coronary syndrome with elevated cardiac biomarkers. The patient’s risk of bleeding should be carefully assessed before treatment is initiated and the risks and benefits of rivaroxaban in combination with aspirin plus clopidogrel or with aspirin alone, compared with aspirin plus clopidogrel or aspirin alone should be discussed with the patient. A decision on continuation of treatment should be taken no later than 12 months after starting treatment. www.nice.org.uk/guidance/ta335 ▶Rivaroxaban for preventing atherothrombotic events in people with coronary or peripheral artery disease (October 2019) NICE TA607 Rivaroxaban (Xarelto ®) plus aspirin is recommended within its marketing authorisation, as an option for preventing atherothrombotic events in adults with coronary artery disease or symptomatic peripheral artery disease who are at high risk of ischaemic events. www.nice.org.uk/guidance/ta607 Scottish Medicines Consortium (SMC) decisions SMC No. 519/08 The Scottish Medicines Consortium has advised (December 2008) that rivaroxaban (Xarelto ®) is accepted for use within NHS Scotland for the prevention of venous thromboembolism in adults undergoing elective hip or knee replacement surgery. SMC No. 756/12 The Scottish Medicines Consortium has advised (February Cardiovascular system 2012) that rivaroxaban (Xarelto ®) is accepted for restricted use within NHS Scotland for the prevention of stroke and systemic embolism in adults with non-valvular atrial fibrillation with one or more risk factors, such as congestive heart failure, hypertension, age 75 years, diabetes mellitus, prior stroke or transient ischaemic attack. Its use is restricted to patients with poor INR control despite compliance with coumarin anticoagulant therapy, or to patients who are allergic to, or unable to tolerate, a coumarin anticoagulant. SMC No. 755/12 The Scottish Medicines Consortium has advised (February 2012) that rivaroxaban (Xarelto ®) is accepted for use within NHS Scotland for the treatment of deep-vein thrombosis (DVT), and prevention of recurrent DVT and pulmonary embolism following an acute DVT in adults. SMC No. 852/13 The Scottish Medicines Consortium has advised (March 2013) that rivaroxaban (Xarelto ®) is accepted for use within NHS Scotland for the treatment of pulmonary embolism (PE), and prevention of recurrent deep-vein thrombosis and PE in adults. SMC No. SMC2128 The Scottish Medicines Consortium has advised (February 2019) that rivaroxaban (Xarelto ®) is accepted for restricted use within NHS Scotland in combination with acetylsalicylic acid for the prevention of atherothrombotic events in adults with stable coronary artery disease that does not require dual antiplatelet therapy.
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Extracted information for Rivaroxaban only.
MHRA/CHM ADVICE: DIRECT-ACTING ORAL ANTICOAGULANTS (DOACS): INCREASED RISK OF RECURRENT THROMBOTIC EVENTS IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME (JUNE 2019) A clinical trial has shown an increased risk of recurrent thrombotic events associated with rivaroxaban compared with warfarin, in patients with antiphospholipid syndrome and a history of thrombosis. There may be a similar risk associated with other DOACs. Healthcare professionals are advised that DOACs are not recommended in patients with antiphospholipid syndrome, particularly high-risk patients who test positive for all three antiphospholipid tests—lupus anticoagulant, anticardiolipin antibodies, and anti-beta2 glycoprotein I antibodies. Continued treatment should be reviewed in these patients to determine if appropriate, and switching to a vitamin K antagonist such as warfarin should be considered. MHRA/CHM ADVICE: RIVAROXABAN (XARELTO ®): REMINDER THAT 15 MG AND 20 MG TABLETS SHOULD BE TAKEN WITH FOOD (JULY Cardiovascular system 2019) The MHRA has received a small number of reports suggesting a lack of efficacy (thromboembolic events) in patients taking 15 mg or 20 mg rivaroxaban tablets on an empty stomach. Healthcare professionals are advised to remind patients to take rivaroxaban 15 mg or 20 mg tablets with food. In those who have difficulty swallowing, these tablets can be crushed and mixed with water or apple puree immediately before, and followed by food immediately after, ingestion.
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→Appendix 1: rivaroxaban
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▶Common or very common Anaemia. asthenia. constipation . diarrhoea. dizziness. fever. gastrointestinal discomfort. haemorrhage. headache. hypotension. menorrhagia. nausea. oedema. pain in extremity. post procedural anaemia. renal impairment. skin reactions. vomiting. wound complications ▶Uncommon Angioedema. dry mouth. hepatic disorders. hypersensitivity. intracranial haemorrhage. malaise. syncope. tachycardia. thrombocytopenia. thrombocytosis ▶Rare or very rare Severe cutaneous adverse reactions (SCARs). vascular pseudoaneurysm
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Manufacturer advises avoid—toxicity in animal studies.
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Manufacturer advises avoid—present in milk in animal studies.
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Manufacturer advises avoid in hepatic disease with coagulopathy and clinically-relevant bleeding risk including patients with moderate to severe cirrhosis.
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Manufacturer advises caution if creatinine clearance 15–29 mL/minute; avoid if creatinine clearance less than 15 mL/minute. Use with caution if concomitant use of drugs that increase plasma- rivaroxaban concentration (consult product literature). Dose adjustments ▶When used for Treatment of deep-vein thrombosis or pulmonary embolism Following the first 21 days of treatment for deep-vein thrombosis or pulmonary embolism, the usual dose of 20 mg once daily can be given, but manufacturer advises consider reducing to 15 mg once daily if creatinine clearance 15–49 mL/minute and the risk of bleeding outweighs the risk of recurrent deep-vein thrombosis or pulmonary embolism. ▶When used for Prophylaxis of recurrent deep-vein thrombosis or pulmonary embolism When the recommended dose is 20 mg once daily, manufacturer advises consider reducing to 15 mg once daily if creatinine clearance 15–49 mL/minute and the risk of bleeding outweighs the risk of recurrent deep-vein thrombosis or pulmonary embolism. ▶When used for Prophylaxis of stroke and systemic embolism in patients with non-valvular atrial fibrillation Manufacturer advises reduce dose to 15 mg once daily if creatinine clearance 15–49 mL/minute.
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▶Patients should be monitored for signs of bleeding or anaemia; treatment should be stopped if severe bleeding occurs. ▶No routine anticoagulant monitoring required (INR tests are unreliable).
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Extracted information for Rivaroxaban only.
Tablets may be crushed and mixed with water or apple puree just before administration.
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There can be variation in the licensing of different medicines containing the same drug. Tablet CAUTIONARY AND ADVISORY LABELS 21 (15 and 20 mg tablets) ▶Xarelto (Bayer Plc) A Rivaroxaban 2.5 mg Xarelto 2.5mg tablets | 56 tablet P £50.40 DT = £50.40 Rivaroxaban 10 mg Xarelto 10mg tablets | 10 tablet P £18.00 | 30 tablet P £54.00 DT = £54.00 | 100 tablet P £180.00 Rivaroxaban 15 mg Xarelto 15mg tablets | 14 tablet P £25.20 | 28 tablet P £50.40 DT = £50.40 | 42 tablet P £75.60 | 100 tablet P £180.00 Rivaroxaban 20 mg Xarelto 20mg tablets | 28 tablet P £50.40 DT = £50.40 | 100 tablet P £180.00 ANTITHROMBOTIC DRUGS › HEPARINOIDS
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Extracted information for Rivaroxaban only.
Patients should be provided with an alert card and advised to keep it with them at all times.
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Filter the extracted dose blocks for this individual drug.
First line only; read the complete Indications and dose section above.
10 mg once daily for 2 weeks, to be started
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 159
First line only; read the complete Indications and dose section above.
10 mg once daily for 5 weeks, to be started
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 159
First line only; read the complete Indications and dose section above.
Initially 15 mg twice daily for 21 days, then
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 159
First line only; read the complete Indications and dose section above.
10 mg once daily, following completion of at
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 159
First line only; read the complete Indications and dose section above.
20 mg once daily, to be taken with food
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 159
First line only; read the complete Indications and dose section above.
2.5 mg twice daily usual duration 12 months
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 159
First line only; read the complete Indications and dose section above.
2.5 mg twice daily
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 159