Edoxaban

Direct inhibitor of activated factor X with a rapid onset of action.

Trade names Lixiana, Savaysa

Administered orally once daily.

A reversible direct factor Xa inhibitior with linear and predictable pharmacokinetic profile.

62% oral bioavailability.

Half-life 10 to 14 hours.

Metabolism is minimal via hydrolysis.

Time to peak levels 1 to 2 hours after intake.

Renal elimination 50%.

Achieves maximum concentrations within one-two hours, and 50% excreted by the kidneys.

Patients with low bodyweight, moderate to severe renal dysfunction, with concomitant use of a P-glycoprotein inhibitor should have a dose reduction by 50%.

In a randomized double-blind noninferiority study patients with acute venous thromboembolism who had received initially heparin were randomized to receive Edoxaban 60 mg daily or 30 mg daily or to receive warfarin: patients received the study drugs for 3 to 12 months and Edoxaban was not inferior to standard care and caused significantly less bleeding in a broad spectrum of patients with venous thromboembolism including severe pulmonary embolus (Hokusai-VTE Investigators).

In a randomized, double-blind, double dummy trial comparing two once daily regimens of Edoxaban and warfarin in 21,105 patients with moderate to high-risk atrial fibrillation and the median follow-up of 2.8 years: primary efficacy endpoint stroke or systemic embolism-both once daily regimens were not inferior to waffling when respect to the prevention of stroke for systemic embolism and were associated with significant lower rates of bleeding and death from cardiovascular causes (ENGAGE AF-TIMI 48 Investigators).

In the above study the high dose of 60 mg of the Edoxaban regimen tends to be more effective than warfarin.

In the above study the incidence of hemorrhagic stroke and the rate of death from cardiovascular causes were significantly lower in the Edoxaban regimens than with warfarin.

Stroke prevention in nonvalvular atrial fibrillation is 60 mg orally daily but with creatinine clearance 15-50 mls per minute 30 mg orally daily.

In patients with atrial fibrillation and stable coronary artery disease, edoxaban monotherapy led to lower risk of composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, or major bleeding or clinically relevant non-major bleeding at 12 months than dual antithrombotic therapy.