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 to prevent thrombotic complications. Edoxaban has been linked to a low rate of serum aminotransferase elevations during therapy, but has not been implicated in cases 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 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 fourth 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 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.
Edoxaban is associated with serum aminotransferase elevations
≥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 experience in large numbers of patients treated for extend periods of time is limited.
Likelihood score: E* (suspected but unproven 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 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, if it occurs at all. There is no reason to suspect that there is cross sensitivity to hepatic injury among the various anticoagulants including other factor Xa inhibitors.
REPRESENTATIVE TRADE NAMES
Edoxaban – Savaysa®
Product labeling at DailyMed, National Library of Medicine, NIH
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References updated: 09 February 2018
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