Drug reference
Edoxaban is a direct and reversible inhibitor of activated factor X (factor Xa), which prevents conversion of prothrombin to thrombin and prolongs clotting time, thereby reducing the risk of thrombus formation.
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Prophylaxis of stroke and systemic embolism in non- valvular atrial fibrillation, in patients with at least one risk factor (such as congestive heart failure, hypertension, aged 75 years and over, diabetes mellitus, previous stroke or transient ischaemic attack) ▶BY MOUTH ▶Adult (body-weight up to 61 kg): 30 mg once daily ▶Adult (body-weight 61 kg and above): 60 mg once daily Treatment of deep-vein thrombosis | Prophylaxis of recurrent deep-vein thrombosis | Treatment of pulmonary embolism | Prophylaxis of recurrent pulmonary embolism ▶BY MOUTH ▶Adult (body-weight up to 61 kg): 30 mg once daily, duration of treatment adjusted according to risk factors—consult product literature, treatment should follow initial use of parenteral anticoagulant for at least 5 days ▶Adult (body-weight 61 kg and above): 60 mg once daily, duration of treatment adjusted according to risk factors—consult product literature), treatment should follow initial use of parenteral anticoagulant for at least 5 days
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DUE TO INTERACTIONS Cardiovascular system ▶Manufacturer advises max. dose of 30 mg once daily with concurrent ciclosporin, dronedarone, erythromycin, or ketoconazole. DOSE EQUIVALENCE AND CONVERSION ▶For information on changing from, or to, other anticoagulants, consult product literature.
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Active bleeding. antiphospholipid syndrome (increased risk of recurrent thrombotic events). arteriovenous malformations. current or recent gastro- intestinal ulceration. hepatic disease (associated with coagulopathy and clinically relevant bleeding risk). known or suspected oesophageal varices. major intraspinal or intracerebral vascular abnormalities. presence of malignant neoplasms at high risk of bleeding. recent brain or spinal injury. recent brain, spinal or ophthalmic surgery . recent intracranial haemorrhage. uncontrolled severe hypertension. vascular aneurysms CONTRA-INDICATIONS, FURTHER INFORMATION ▶Risk for major bleeding Edoxaban treatment is contra- indicated in patients with significant risk factors for major bleeding, these include those listed above.
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Moderate to severe mitral stenosis (safety and efficacy not established). prosthetic heart valve (safety and efficacy not established). risk of bleeding. surgery CAUTIONS, FURTHER INFORMATION ▶Surgery Manufacturer recommends to discontinue treatment at least 24 hours before a surgical procedure; the risk of bleeding should be weighed against the urgency of the intervention—consult product literature. ▶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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NICE decisions ▶Edoxaban for treating and preventing deep vein thrombosis and pulmonary embolism (August 2015) NICE TA354 Edoxaban (Lixiana ®) is recommended as an option for treating and preventing recurrent deep vein thrombosis and pulmonary embolism. www.nice.org.uk/guidance/ta354 ▶Edoxaban for preventing stroke and systemic embolism in people with non-valvular atrial fibrillation (September 2015) NICE TA355 Edoxaban (Lixiana ®) is an option for the prevention of stroke and systemic embolism in non-valvular atrial fibrillation, with one or more 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 edoxaban treatment compared to warfarin, apixaban, dabigatran etexilate, and rivaroxaban should be discussed with the patient. www.nice.org.uk/guidance/ta355
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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.
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→Appendix 1: edoxaban
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▶Common or very common Anaemia. haemorrhage. nausea. skin reactions Cardiovascular system ▶Uncommon CNS haemorrhage SIDE-EFFECTS, FURTHER INFORMATION Should a bleeding complication arise in a patient receiving edoxaban, the manufacturer recommends to delay the next dose or treatment should be discontinued as appropriate.
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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 caution in mild to moderate impairment, or if liver transaminases greater than 2 times the upper limit of normal, or total bilirubin 1.5 times the upper limit of normal or greater; avoid in severe impairment or hepatic disease associated with coagulopathy and clinically relevant bleeding risk.
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Manufacturer advises avoid if creatinine clearance less than 15 mL/minute. Dose adjustments Manufacturer advises use a dose of 30 mg once daily if creatinine clearance 15–50 mL/minute.
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▶Manufacturer advises monitor renal function before treatment and when clinically indicated during treatment; monitor hepatic function before treatment and repeat periodically if treatment duration longer than 1 year. ▶Manufacturer advises monitor for signs of mucosal bleeding and anaemia in patients at increased risk; treatment should be stopped if severe bleeding occurs. ▶No routine anticoagulant monitoring required (INR tests are unreliable).
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There can be variation in the licensing of different medicines containing the same drug. Tablet CAUTIONARY AND ADVISORY LABELS 10 ▶Lixiana (Daiichi Sankyo UK Ltd) A Edoxaban (as Edoxaban tosilate) 15 mg Lixiana 15mg tablets | 10 tablet P £17.50 DT = £17.50 Edoxaban (as Edoxaban tosilate) 30 mg Lixiana 30mg tablets | 28 tablet P £49.00 DT = £49.00 Edoxaban (as Edoxaban tosilate) 60 mg Lixiana 60mg tablets | 28 tablet P £49.00 DT = £49.00
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Patients should be provided with an alert card and advised to keep it with them at all times.
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30 mg once daily
First-line fragment. Read the complete Indications and Dose section above.
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60 mg once daily
First-line fragment. Read the complete Indications and Dose section above.
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30 mg once daily,
First-line fragment. Read the complete Indications and Dose section above.
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60 mg once daily,
First-line fragment. Read the complete Indications and Dose section above.
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