Trade names Savaysa, Lixiana Routes of
administration Oral Legal status US: ℞-only Protein binding 55% | AHFS/Drugs.com Monograph ATC code B01AF03 (WHO) Molar mass 548.056 g/mol | |
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Pregnancy
category US: C (Risk not ruled out) | ||
Edoxaban (DU-176b, trade names Savaysa, Lixiana) is an oral anticoagulant drug which acts as a direct factor Xa inhibitor. It was developed by Daiichi Sankyo and approved in July 2011 in Japan for prevention of venous thromboembolisms (VTE) following lower-limb orthopedic surgery. It was also approved by the FDA in January 2015 for the prevention of stroke and non–central-nervous-system systemic embolism.
Contents
Medical uses
US FDA-labeled indications:
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5 to 10 days of initial therapy with a parenteral anticoagulant. To reduce the risk of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (NVAF)Contraindications
Edoxaban is contraindicated in nonvalvular atrial fibrillation (NVAF) patients with a creatinine clearance (CrCl) greater than 95 mL/minute because of an increased risk of ischemic stroke compared to warfarin.
It is also contraindicated in patients with active pathological bleeding.
Warnings
Spinal or epidural hematomas resulting in long-term or permanent paralysis may occur with neuraxial anesthesia (epidural or spinal anesthesia) or spinal/epidural puncture; the risk is increased by the use of indwelling epidural catheters, concomitant administration of other drugs that affect hemostasis (eg, NSAIDs, platelet inhibitors, other anticoagulants), in patients with a history of traumatic or repeated epidural or spinal punctures, a history of spinal deformity or surgery, or if optimal timing between the administration of edoxaban and neuraxial procedures is not known.
Adverse effects
More common
Less common
Rare
Mechanism of action
Edoxaban inhibits free factor Xa and prothrombinase activity and inhibits thrombin-induced platelet aggregation. Inhibition of factor Xa in the coagulation cascade reduces thrombin generation and thrombus formation.
Factor Xa
Factor Xa (FXa) is an essential blood coagulation factor that is responsible for the initiation of the coagulation cascade. FXa cleaves prothrombin to its active form thrombin, which then acts to convert soluble fibrinogen to insoluble fibrin and to activate platelets. Stabilization of the platelet aggregation by fibrin mesh ultimately leads to clot formation.
Related medications
A number of anticoagulants inhibit the activity of Factor Xa. Unfractionated heparin (UFH), low molecular weight heparin (LMWH), and fondaparinux inhibit the activity of factor Xa indirectly by binding to circulating antithrombin (AT III). These agents must be injected. Warfarin, phenprocoumon, and acenocoumarol are orally active vitamin K antagonists (VKA) which decrease hepatic synthesis of a number of coagulation factors, including Factor X. In recent years, a new series of oral, direct acting inhibitors of Factor Xa have entered clinical development. These include rivaroxaban, apixaban, betrixaban, LY517717, darexaban (YM150), and edoxaban (DU-176b).