Edoxaban

Abstract

Edoxaban is an oral direct factor Xa inhibitor that is currently undergoing investigation in phase III clinical trials for the prevention of stroke in patients with atrial fibrillation (AF) and for the prevention and treatment of venous thromboembolic events (VTE). Factor Xa is an attractive target for anticoagulant treatment, as it is the primary and rate-limiting source of amplification in the coagulation cascade. Edoxaban is a competitive inhibitor of factor Xa and has >10 000-fold greater selectivity for factor Xa relative to thrombin. In phase I clinical trials, the anticoagulant effects of edoxaban included dose-dependent increases in activated partial thromboplastin time and prothrombin time following single edoxaban doses of 10-150 mg and after multiple ascending doses (60 mg twice daily, 90 mg daily and 120 mg daily). The anticoagulant effects of edoxaban were rapid in onset (time to peak plasma concentration 1-2 hours) and sustained for up to 24 hours. Prolongation of bleeding time in 8% of subjects was >9.5 minutes (none of which appeared to be clinically significant) 2 hours after initial dosing, and was independent of edoxaban dose, formulation or dietary state. In general, plasma edoxaban concentrations were linearly correlated with coagulation parameters. Phase II clinical trials in patients with AF and VTE suggest that the edoxaban 30 mg once-daily and 60 mg once-daily regimens had a similar or better safety profile compared with dose-adjusted warfarin (international normalized ratio 2.0-3.0) in terms of bleeding events, and that edoxaban was not associated with hepatotoxicity. In addition, edoxaban was associated with statistically significant dose-dependent reductions in VTE after orthopaedic surgery compared with placebo or dalteparin sodium. Further clinical investigation of the efficacy and safety of once-daily edoxaban is being conducted in phase III clinical trials in comparison with warfarin in patients with AF in the phase III ENGAGE AF-TIMI 48 trial (NCT00781391), and in comparison with low-molecular weight heparin/warfarin in the prevention of recurrent VTE in patients with symptomatic deep vein thrombosis and/or pulmonary embolism in the HOKUSAI VTE trial (NCT00986154).

Peri-procedural management of patients taking oral anticoagulants

“…12 38 39 Edoxaban reaches peak plasma concentration rapidly after administration (1-2 h) and its half life is similar to that of other direct Xa inhibitors (9-10 h); about 35% of the drug is renally excreted. 20 25 28 Bridging therapy Because the offset and onset of the effect of VKAs such as warfarin and phenprocoumon are slow, when stopped and then restarted around the time of a procedure, there Assessing the risk of peri-procedural hemorrhage Bleeding complications are an important concern in patients taking any oral anticoagulant, and tools have been developed to aid decision making for patients with non-valvular atrial fibrillation. The HAS-BLED score is a widely used example.…”

Anti-Coagulation and Deep Brain Stimulation: Never the Twain Shall Meet?

“…Newer direct factor Xa (e.g. rivaroxaban, apixaban, and edoxaban) [13] and thrombin inhibitors (e.g. dabigatran) have demonstrated comparative efficacy with a better side effect profile [14].…”

ANMCO Position Paper: direct oral anticoagulants for stroke prevention in atrial fibrillation: clinical scenarios and future perspectives

“…Apixaban is absorbed by the intestine in its active form (50% in the distal part of the small intestine and ascending colon) and is about 73% metabolised in the liver, involving essentially the P3A4 and P3A5 cytochrome systems, with no active metabolites 19 . Edoxaban is rapidly absorbed by the gastrointestinal system and about 50% metabolised in the liver, although with little involvement of the P3A4 cytochrome system, 20 and about 50% in the kidneys 20 …”