edoxaban
Direct factor Xa inhibitor· Brands: Lixiana, Savaysa, RoteasPO
Mechanism of action
Edoxaban is a selective, reversible, direct inhibitor of factor Xa. It binds to the active site of factor Xa, blocking the conversion of prothrombin to thrombin, thereby reducing thrombin generation and inhibiting thrombus formation.
Pharmacokinetics
Edoxaban is administered orally. It is rapidly absorbed with peak plasma concentrations occurring at 1 to 2 hours. Bioavailability is approximately 62%. Plasma protein binding is about 55%. Edoxaban is metabolised minimally through CYP3A4 and other pathways; it is a substrate of P-glycoprotein. Elimination is primarily renal, with approximately 50% of the dose excreted unchanged in urine. The terminal half-life is 10 to 14 hours, which is prolonged in renal impairment.
Indications & dosing
Prevention of stroke and systemic embolism in non-valvular atrial fibrillation
Reduce to 30 mg once daily if CrCl 15-50 mL/min, body weight <=60 kg, or concomitant use of certain P-gp inhibitors (e.g., verapamil, quinidine).
- adult · PO: 60 mg once daily · Reduce to 30 mg once daily if CrCl 15-50 mL/min, body weight <=60 kg, or concomitant use of certain P-gp inhibitors (e.g., verapamil, quinidine).
Treatment of deep vein thrombosis and pulmonary embolism, and prevention of recurrent venous thromboembolism
Administer after initial 5-10 days of parenteral anticoagulation. Same dose reduction criteria as for atrial fibrillation.
- adult · PO: 60 mg once daily · Administer after initial 5-10 days of parenteral anticoagulation. Same dose reduction criteria as for atrial fibrillation.
Contraindications & precautions
- Active clinically significant bleeding · Including gastrointestinal bleeding or intracranial haemorrhage.
- Hypersensitivity to edoxaban or any excipient
- Hepatic disease associated with coagulopathy and clinically relevant bleeding risk
- Prosthetic heart valves or moderate to severe mitral stenosis
- Severe renal impairment with creatinine clearance <15 mL/min
- Pregnancy and breastfeeding
- Creatinine clearance >95 mL/min · Not recommended due to increased bleeding risk.
- Monitor renal function before and during treatment; reduce dose to 30 mg once daily in moderate renal impairment (creatinine clearance 15-50 mL/min).
- Avoid in patients with creatinine clearance >95 mL/min because of increased bleeding risk.
- Assess bleeding risk regularly, especially in elderly patients, low body weight (<60 kg), and those taking antiplatelets or NSAIDs.
- Use with caution in hepatic impairment, and avoid in patients with hepatic coagulopathy.
- If switching to or from other anticoagulants, follow local protocols and observe appropriate washout periods.
- Missed doses: take as soon as remembered, but do not double take to make up for a missed dose.
Adverse effects
- Bleeding, including gastrointestinal and intracranial haemorrhageserious
- Anaemia
- Nausea
- Diarrhoea
- Dyspepsia
- Headache
- Rash
- Increased liver enzymesserious
- Angioedemaserious
Interactions
- clarithromycinmajorAvoid coadministration unless the benefit clearly outweighs the risk. If unavoidable, consider reducing the edoxaban dose by half (for example, from 60 mg to 30 mg once daily). Monitor the patient closely for signs of bleeding, and assess renal function at baseline and periodically. Consider an alternative antibiotic with minimal P-gp inhibition, such as azithromycin, if clinically appropriate. Instruct the patient to seek urgent medical attention if they develop unusual bleeding.
- clopidogrelmajorAvoid the combination unless the anticipated benefit outweighs the risk. When co-prescription is necessary, use the lowest effective doses and limit the duration of dual therapy. Monitor the patient closely for signs of bleeding, including haemoglobin and haematocrit checks, and assess for occult blood loss. Consider using a proton pump inhibitor for gastroprotection. Evaluate renal function regularly and adjust edoxaban dose as needed. Review the indication for clopidogrel at each visit and discontinue when no longer required.
- aspirinmajorAvoid concomitant use unless the benefit of antiplatelet therapy outweighs the bleeding risk (e.g., acute coronary syndrome or coronary stenting). If combined treatment is necessary, use the lowest effective aspirin dose, limit the duration of dual therapy, and monitor closely for signs of bleeding (e.g., haemoglobin, stools). Review the need for aspirin regularly and consider gastroprotection with a proton pump inhibitor.
Renal & hepatic adjustment
- eGFR 0–15: CrCl <15 ml/min: not recommended; use alternative anticoagulant. (avoid)
- eGFR 15–50: Reduce dose to 30 mg once daily.
- eGFR 50–95: No dose adjustment required (60 mg once daily).
- eGFR 95–300: CrCl >95 ml/min: not recommended for stroke prevention in non-valvular AF; for VTE treatment, no dose adjustment required.
- Hepatic impairment (mild): No dose adjustment required (Child-Pugh A).
- Hepatic impairment (moderate): Not recommended (Child-Pugh B); consider alternative anticoagulant. (avoid)
- Hepatic impairment (severe): Not recommended (Child-Pugh C). (avoid)
Monitoring, pregnancy & toxicity
- Renal function (serum creatinine, calculated creatinine clearance) · Baseline, then at least annually; more frequently if renal impairment or intercurrent illness.
- Hepatic function · Baseline and periodically in patients with hepatic impairment.
- Signs of bleeding (e.g., bruising, melaena, haematuria, Hb level) · Throughout treatment.
- Concomitant medication (P-gp inhibitors/inducers, anticoagulants, antiplatelets) · At each review.
- Compliance and bleeding risk assessment · At each review.
- Pregnancy: Contraindicated in pregnancy; women of childbearing potential should use effective contraception during treatment.
- Toxicity: Bleeding (including intracranial, GI, and other haemorrhage), which may be major or minor. · Stop edoxaban. Provide supportive care (volume resuscitation, blood transfusions). For severe bleeding, consider prothrombin complex concentrate (PCC) or activated PCC per local protocol. Activated charcoal may be useful if recent ingestion. There is no specific antidote; haemodialysis is not effective.
Clinical notes
No specific reversal agent is approved for edoxaban (andexanet alfa is approved only for apixaban and rivaroxaban); prothrombin complex concentrate is used for severe bleeding.
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BNF; local formulary