Edoxaban is a selective inhibitor of factor Xa, a serine endopeptidase of the clotting cascade required for cleavage of prothrombin into thrombin.
Administration of edoxaban results in prolongation of clotting time tests such as aPTT (activated partial thromboplastin time), PT (prothrombin time), and INR (international normalized ratio).
Edoxaban is not extensively metabolized by CYP3A4 resulting in minimal drug-drug interactions. However, it does interact with drugs that inhibit p-gp (p-glycoprotein), which is used to transport edoxaban across the intestinal wall. Unchanged edoxaban is the predominant form in plasma. There is minimal metabolism via hydrolysis (mediated by carboxylesterase 1), conjugation, and oxidation by CYP3A4. The predominant metabolite M-4, formed by hydrolysis, is human-specific and active and reaches less than 10% of the exposure of the parent compound in healthy subjects. Exposure to the other metabolites is less than 5% of exposure to edoxaban.
Premature discontinuation of any oral anticoagulant, including edoxaban, in the absence of adequate alternative anticoagulation increases the risk of ischemic events. If edoxaban is discontinued for reasons other than pathological bleeding or completion of a course of therapy, consider the use of another anticoagulant. Edoxaban increases the risk of potentially fatal major bleeding such as intracranial hemorrhage and gastrointestinal bleeding. Patients should be educated on how to watch for signs of major and minor bleeding and when to seek medical help. Co-administration of other anti-coagulants, anti-platelets, or thrombolytics may increase the risk of bleeding and should therefore be avoided.