Introduction
Edoxaban (brand name Savaysa®) is an oral direct factor Xa inhibitor anticoagulant that belongs to the class of novel oral anticoagulants (NOACs). Approved by the FDA in 2015, edoxaban provides an alternative to warfarin and other anticoagulants for stroke prevention and venous thromboembolism treatment. It offers predictable pharmacokinetics with fixed dosing and requires less monitoring than vitamin K antagonists.
Mechanism of Action
Edoxaban selectively and reversibly inhibits free and clot-bound factor Xa, as well as prothrombinase activity. By inhibiting factor Xa—a key component in the coagulation cascade—edoxaban prevents the conversion of prothrombin to thrombin, thereby reducing thrombus formation. Unlike indirect factor Xa inhibitors, edoxaban directly inhibits factor Xa without requiring antithrombin III as a cofactor.
Indications
- Reduction of risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation
- Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5-10 days of initial parenteral anticoagulation
Dosage and Administration
Non-valvular atrial fibrillation:- 60 mg once daily
- Reduce to 30 mg once daily if any of the following:
- CrCl 15-50 mL/min - Body weight ≤60 kg - Concomitant use of certain P-gp inhibitors (verapamil, quinidine, dronedarone)
DVT/PE treatment:- 60 mg once daily after initial parenteral anticoagulation
- Reduce to 30 mg once daily if CrCl 15-50 mL/min or body weight ≤60 kg
- Administer with or without food
- Avoid use in patients with CrCl >95 mL/min due to reduced efficacy
- Not recommended in patients with CrCl <15 mL/min
Pharmacokinetics
Absorption: Rapidly absorbed with peak concentrations in 1-2 hours; bioavailability approximately 62% Distribution: Volume of distribution 107 L; 40-59% protein bound Metabolism: Minimal metabolism via hydrolysis, conjugation, and CYP3A4 oxidation Elimination: Half-life 10-14 hours; primarily eliminated unchanged in feces (50%) and urine (50%) Special populations: Exposure increases with renal impairment; no significant adjustment needed for hepatic impairment (Child-Pugh A and B)Contraindications
- Active pathological bleeding
- Hypersensitivity to edoxaban or any component
- Patients with mechanical heart valves (not studied, not recommended)
Warnings and Precautions
Bleeding risk: Increased risk of serious and potentially fatal bleeding Spinal/epidural hematoma risk: With neuraxial anesthesia or spinal puncture Premature discontinuation: Increased risk of thrombotic events Renal impairment: Requires dose reduction; avoid in CrCl >95 mL/min Hepatic impairment: Not recommended in patients with moderate or severe impairment (Child-Pugh B and C) Pregnancy: Category C; use only if potential benefit justifies potential risk Labor and delivery: Safety not established Nursing mothers: Decision should be made to discontinue nursing or discontinue drugDrug Interactions
Strong P-gp inhibitors:- Rifampin: Avoid concomitant use
- Cyclosporine, dronedarone, erythromycin, ketoconazole, quinidine, verapamil: Requires dose reduction to 30 mg
- Aspirin, clopidogrel, NSAIDs: Use with caution
- Heparin, warfarin, other anticoagulants: Avoid concomitant use
Adverse Effects
Common (≥1%):- Bleeding (various types)
- Rash
- Abnormal liver function tests
- Anemia
- Major bleeding events
- Spinal/epidural hematoma
- Hypersensitivity reactions
- Hepatic injury
Monitoring Parameters
- Signs and symptoms of bleeding
- Renal function (serum creatinine at baseline and periodically)
- Hemoglobin/hematocrit
- Liver function tests
- Compliance with therapy
- Signs of thrombotic events after discontinuation
Patient Education
- Take exactly as prescribed; do not change dose without medical advice
- Report any signs of bleeding (unusual bruising, red/dark urine, bloody stools)
- Inform all healthcare providers about edoxaban use before any procedures
- Do not discontinue without medical guidance due to stroke risk
- Use reliable contraception if of childbearing potential
- Report any allergic reactions or skin rash
- Be aware of increased fall or injury risk
- Keep all follow-up appointments
References
1. Ruff CT, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962. 2. Giugliano RP, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093-2104. 3. Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369(15):1406-1415. 4. Savaysa® (edoxaban) prescribing information. Daiichi Sankyo, Inc. 2021. 5. January CT, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. J Am Coll Cardiol. 2019;74(1):104-132. 6. Kearon C, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315-352.