Formulary
Edoxaban: Indications, Dosing, Side Effects and Interactions
Edoxaban is a direct and reversible inhibitor of activated factor X (factor Xa), which prevents conversion of prothrombin to thrombin and prolongs clotting...
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Edoxaban: Indications, Dosing, Side Effects and Interactions
Edoxaban is a direct and reversible inhibitor of activated factor X (factor Xa), which prevents conversion of prothrombin to thrombin and prolongs clotting...
Drug action
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.
Indications and dose
**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)**
- **Adult** (By Mouth): (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**
- **Adult** (By Mouth): (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.
Cautions
General cautions: Edoxaban should not be used as an alternative to heparin in pulmonary embolism in patients with haemodynamic instability, or who may receive thrombolysis or pulmonary embolectomy; moderate to severe mitral stenosis (safety and efficacy not established); risk of bleeding; surgery Specific cautions: When used for prophylaxis of stroke and systemic embolism in non-valvular atrial fibrillation Creatinine clearance more than 100 mL/minute (potential for reduced efficacy-evaluate thromboembolic and bleeding risk) Cautions, further information Surgery Discontinue treatment at least 24 hours before a surgical procedure; the risk of bleeding should be weighed against the urgency of the intervention M -consult product literature. Elderly For factor Xa inhibitors, Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) criteria to aid medication reviews (see Prescribing in the elderly for information). Potentially inappropriate: 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 m (contra-indicated in kidney failure; risk of bleeding)
Contraindications
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; prosthetic heart valve (safety and efficacy not established); recent brain or spinal injury; recent brain, spinal or ophthalmic surgery; recent intracranial haemorrhage; significant risk of major bleeding; uncontrolled severe hypertension; use with any other anticoagulant; vascular aneurysms Contra-indications, further information Use with any other anticoagulant Concomitant use with any other anticoagulant is contra-indicated, except when switching therapy, or when heparin is given at doses necessary to maintain an open central venous or arterial catheter or for catheter ablation-use with caution. M
Side effects
Common or very common Abdominal pain; anaemia; dizziness; haemorrhage; headache; nausea; skin reactions Uncommon CNS haemorrhage; thrombocytopenia 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.
Interactions
**Other interactions (13):**
- Apixaban Rivaroxaban Edoxaban Interaction not studied with any of the components of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Gilead.
- Coadministration of apixaban, rivaroxaban or edoxaban is not recommended with Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Gilead.
- Dabigatran etexilate, Edoxaban Dabigatran etexilate, Edoxaban: Serum concentrations may be increased due to P-gp inhibition by lopinavir/ritonavir.
- Clinical monitoring and/or dose reduction of the direct oral anticoagulants (DOAC) should be considered when a DOAC transported by P-gp but not metabolised by CYP3A4, including dabigatran etexilate...
- Caution may be needed in co-administering medicinal products that are known to be substrates of P-gp (such as dabigatran, digoxin, edoxaban, fexofenadine, tacrolimus).
- Dabigatran etexilate Edoxaban Ticagrelor Clopidogrel dabigatran etexilate (150 mg): darunavir/ritonavir 800/100 mg single dose: dabigatran AUC 72% dabigatran C max 64% darunavir/ritonavir...
Pregnancy
Manufacturer advises avoid-toxicity in animal studies.
Breast feeding
Manufacturer advises avoid-present in milk in animal studies.
Hepatic impairment
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.
Renal impairment
Important safety information For edoxaban MHRA/CHM advice: New oral anticoagulants apixaban ( Eliquis ), dabigatran ( Pradaxa ) and rivaroxaban ( Xarelto ) (October 2013) The following contra-indications now apply to all new oral anticoagulants (including edoxaban ( Lixiana ) which was not launched at the release of this advice), for all indications and doses: a lesion or condition, if considered a significant risk factor for major bleeding-see Contra-indications for further information; concomitant treatment with any other anticoagulant agent-see Contra-indications for further information. Healthcare professionals are advised to take caution when deciding to prescribe these anticoagulants to patients with other conditions, undergoing other procedures, and on other treatments, which may increase the risk of major bleeding. The renal function of patients should also be considered. 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-beta 2 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: Direct-acting oral anticoagulants (DOACs): reminder of bleeding risk, including availability of reversal agents (June 2020) The MHRA reminds healthcare professionals to remain vigilant for signs and symptoms of bleeding complications during treatment with edoxaban after ongoing reports of serious, potentially fatal bleeds associated with the use of DOACs. Healthcare professionals are also advised to use edoxaban with caution in patients with increased bleeding risk, and to ensure that those with renal impairment are dosed appropriately and their renal function monitored during treatment. Patients should be counselled on the signs and symptoms of bleeding, and encouraged to read the patient information leaflet. There is currently no specific authorised reversal agent available for edoxaban. MHRA/CHM advice: Warfarin and other anticoagulants: monitoring of patients during the COVID-19 pandemic (October 2020) Healthcare professionals are reminded that: direct-acting oral anticoagulants (DOACs), such as edoxaban, may interact with other medicines (including antibacterials and antivirals)-advice in product literature should be followed to minimise the risk of potential interactions; if patients are switched from warfarin to edoxaban, warfarin treatment should be stopped before edoxaban treatment is started to reduce the risk of over-anticoagulation and bleeding. MHRA/CHM advice: Direct-acting oral anticoagulants (DOACs): reminder of dose adjustments in patients with renal impairment (May 2023) Healthcare professionals are reminded that: exposure to DOACs, such as edoxaban, is increased in patients with renal impairment, and these patients should receive an appropriately adjusted dose-see Renal impairment for further information; such patients should be reviewed regularly during treatment to ensure the dose remains appropriate; renal function should be assessed by calculating creatinine clearance using the Cockcroft and Gault formula.
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Clinical governance
**Author:** MedNext Clinical Team. **Clinical reviewer:** Dr Shameer Deen, MBBS, MS, MRCS. **Sources:** BNF, Indian Pharmacopoeia, CIMS India. **Correction:** Report errors at support@mednext.academy.
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