Indications
Edoxaban is prescribed to minimize the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. It is crucial to note that edoxaban is contraindicated in individuals with a creatinine clearance greater than 95 mL/min due to an increased risk of ischemic stroke when compared to warfarin at its maximum dose of 60 mg. Additionally, edoxaban is utilized in the treatment of deep vein thrombosis and pulmonary embolism, but only after an initial therapy period of 5 to 10 days using a parenteral anticoagulant.
Pharmacodynamics
The administration of edoxaban influences coagulation parameters, resulting in the prolongation of clotting time tests, such as the activated partial thromboplastin time (aPTT), prothrombin time (PT), and international normalized ratio (INR). These effects are indicative of the anticoagulant's mechanism of action in preventing thrombotic events.
Absorption
Edoxaban, when administered orally, reaches peak plasma concentrations within 1 to 2 hours. The absolute bioavailability of the drug is approximately 62%, which suggests a moderate absorption rate from the gastrointestinal tract into systemic circulation.
Metabolism
Edoxaban is not extensively metabolized by the enzyme CYP3A4, which reduces the likelihood of significant drug-drug interactions involving this metabolic pathway. However, edoxaban interacts with drugs that inhibit p-glycoprotein, a transporter protein responsible for translocating edoxaban across the intestinal wall. In plasma, edoxaban predominantly remains in its unchanged form, with minimal metabolism through hydrolysis, conjugation, and oxidation (mediated by CYP3A4). The primary metabolite, M-4, which is active and formed through hydrolysis, is specific to humans and comprises less than 10% of the main compound's exposure in healthy individuals. Exposure to other metabolites is less than 5% of that to edoxaban.
Mechanism of Action
Edoxaban functions as a selective inhibitor of factor Xa, an essential serine endopeptidase within the clotting cascade responsible for the conversion of prothrombin to thrombin. By specifically targeting factor Xa, Edoxaban effectively disrupts this crucial step in the coagulation process, thereby reducing thrombin generation and ultimately diminishing the formation of blood clots. This mechanism highlights Edoxaban's role in managing and preventing thromboembolic disorders.
