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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: February 16, 2023.



Edoxaban is an oral, small molecule inhibitor of factor Xa which is used as an anticoagulant to decrease the risk of venous thromboses, systemic embolization and stroke in patients with atrial fibrillation, and as treatment of deep vein thrombosis and pulmonary embolism. Edoxaban has been linked to a low rate of serum aminotransferase elevations during therapy and to rare instances of clinically apparent acute liver injury.


Edoxaban (e dox' a ban) is a selective inhibitor of the coagulation factor Xa, the last and rate controlling step in the generation of thrombin, the final intermediate in blood coagulation. Inhibiting thrombin prevents the conversion of fibrinogen to fibrin and subsequent cross linking of fibrin monomers, platelet activation and amplification of coagulation activation. Edoxaban has been shown to be as effective an anticoagulant as warfarin in preventing stroke and systemic embolization in patients with atrial fibrillation. Clinical trials have also shown that edoxaban can decrease the risk of complications of deep vein thrombosis and pulmonary embolism. Edoxaban was approved for use in the United States in 2015, the third direct factor Xa inhibitor to be approved. Current indications are for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and for treatment of patients with deep vein thrombosis and pulmonary embolism. Edoxaban is not recommended in patients with a creatinine clearance of greater than 95 cc/minute as such patients had increases in ischemic strokes compare to patients treated with warfarin. Edoxaban is available in 15, 30 and 60 mg tablets under the commercial name Savaysa. The usual dose is 60 mg daily. Unlike warfarin, edoxaban and the other oral direct thrombin and factor Xa inhibitors do not require monitoring of bleeding time or INR and rarely require dose adjustments. Side effects are not common, but can include bleeding, headache, gastrointestinal upset, and rash. Rare, but potential severe adverse reactions include major bleeding including hemorrhagic stroke as well as spinal or epidural hematomas, and increased risk of ischemic events in patients with premature discontinuation.


Edoxaban is associated with serum aminotransferase elevations greater than 3 times the upper limit of normal in 2% to 5% of treated patients. This rate is similar or lower than rates with warfarin or comparator arms. The elevations are generally transient and not associated with symptoms or jaundice. In premarketing studies, no instances of clinically apparent liver injury were reported, but there was little experience in large numbers of patients treated for extend periods of time. In large health care databases, the rate of liver injury has been somewhat less with edoxaban than rivaroxaban and apixaban, but the numbers of patients treated with edoxaban has been limited and the nature of the liver injury not described.

Likelihood score: D (possible race cause of clinically apparent liver injury).

Mechanism of Injury

Edoxaban is eliminated largely unchanged in the urine and has minimal hepatic metabolism. It is a substrate of P-glycoprotein, and its serum concentrations can be affected by inducers (rifampin) and inhibitors of this transport protein. The cause of the serum enzyme elevations during therapy with edoxaban is unknown, but the rate of such elevations was usually lower or no different than with comparator anticoagulants.

Outcome and Management

The serum enzyme elevations during edoxaban therapy have been mild-to-moderate in severity, but asymptomatic and rapidly reversible often even without stopping therapy. Clinically apparent liver injury due to edoxaban appears to be rare and has not been well documented. There is no reason to suspect that there is cross sensitivity to hepatic injury among the various anticoagulants including other factor Xa inhibitors.

Drug Class: Antithrombotic Agents, Anticoagulants

Other Drugs in the Subclass, Anticoagulants, Newer Direct Oral Anticoagulants: Apixaban, Betrixaban, Fondaparinux, Rivaroxaban



Edoxaban – Savaysa®




Product labeling at DailyMed, National Library of Medicine, NIH


Edoxaban 480449-70-5 C24-H30-Cl-N7-O4-SSID:135263753


References updated: 16 February 2023

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    (Among 13,698 patients with atrial fibrillation started on anticoagulant therapy and followed in the Hong Kong Clinical Database and Reporting system between 2010 and 2016, 513 [2.8%] developed evidence of liver injury and propensity matching indicated that liver injury was less frequent [2.1% vs 3.4%], although more severe with oral anticoagulants than with warfarin).
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    (Among 1213 patients with atrial fibrillation started on edoxaban between 2016 and 2020 and followed in the Hong Kong Clinical Database and Reporting System, 19 [1.5%] developed evidence of liver injury, a rate below that previously reported for warfarin [3.7%], apixaban [2.5%], and rivaroxaban [2.1%]).
  • De Caterina R, Kim YH, Koretsune Y, Wang CC, Yamashita T, Chen C, Reimitz PE, et al. Safety and effectiveness of edoxaban in atrial fibrillation patients in routine clinical practice: one-year follow-up from the Global Noninterventional ETNA-AF Program. J Clin Med. 2021;10:573. [PMC free article: PMC7913627] [PubMed: 33546442]
    (Among 26,823 adults from Europe and Asia with atrial fibrillation enrolled in a postmarketing study of edoxaban, major complications were uncommon including annualized event rates of major bleeding episodes of 1.1%, strokes of 1.1%, cardiovascular mortality in 1.2% and all-cause mortality in 3%; rates of liver injury were not provided).
  • Ma J, Chalasani NP, Schwantes-An L, Björnsson ES. Review article: the safety of anticoagulants and antiplatelet agents in patients with cirrhosis. Aliment Pharmacol Ther. 2023;57:52–71. [PubMed: 36373544]
    (Review of the safety of anticoagulant use in patients with cirrhosis mentions that drug induced liver injury is uncommon in patients with preexisting cirrhosis, at least in those with compensated [Child’s Class A] or mildly compensated [Child’s Class B] cirrhosis).


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