Edoxaban in Atrial Fibrillation and Venous Thromboembolism—Ten Key Questions and Answers: A Practical Guide

Abstract

Edoxaban is the fourth non-vitamin K antagonist oral anticoagulant now available for clinical use in the prevention of stroke/systemic embolism in atrial fibrillation (AF) and in the treatment of venous thromboembolism (VTE), after the completion of large-scale randomized comparative clinical trials with the vitamin K antagonist warfarin. Edoxaban has some peculiar pharmacological properties and outcome data. Here a group of experts in AF and VTE answers a set of questions on its practical use, trying to define the profile of patients that would be most appropriate for its use.

Risk management in patients with atrial fibrillation and comorbid conditions: potentialities of edoxaban

“…Для практического врача это означает, что сильное ингибирование или индукция CYP P450 3A4 может влиять на концентрацию этих двух ПОАК в плазме крови пациентов. При совместном назначении с сильными ингибиторами CYP P450 3A4 и P-гликопротеина (дронедарон или азольные антимикотики, такие как итраконазол, кетоконазол, позаконазол, вориконазол) концентрации в плазме рива роксабана и апиксабана могут увеличиваться [27]. Это характеризует эдоксабан как лекарственный препарат в высокой степени безопасный у пациентов с ФП и коморбидностью, с учетом возможных лекарственных взаимодействий.…”

Pharmacogenetics of Novel Oral Anticoagulants: A Review of Identified Gene Variants & Future Perspectives

“…Its half-life is in the range of 8-10 h, while peak plasma concentration is achieved within 1-2 h after ingestion [54,55]. Although edoxaban has notably less drug-drug interactions than other NOACs, interactions with P-gp inhibitors were proven, as these drugs are capable of causing increased plasma concentrations of edoxaban, while P-gp inducers were shown to decrease edoxaban concentration [56,57]. In addition, food intake, age, gender and ethnicity have no influence on drug pharmacological profile.…”

“…In 2014, there were no approved antidotes for edoxaban, with research suggesting that changes in prothrombin time caused by edoxaban can be reduced via the activity of PCC, aPCC and rFVIIa [59]. According to the latest reports, andexanet alfa is considered to be approved as an edoxaban antidote by EMA, while four-factor PCC is now used to reverse the effects of edoxaban within a 30-min frame after the drug delivery [56]. In addition, another antidote is currently being developed.…”

Pharmacological and Non-pharmacological Treatments for Stroke Prevention in Patients with Atrial Fibrillation

“…Edoxaban, a direct factor Xa inhibitor, is the fourth NOAC approved for prevention of stroke and other thromboembolic events in patients with atrial fibrillation [ 97 ].…”

“…Although edoxaban is promoted as trouble-free concerning CYP450 system interactions because it is metabolized via hydrolysis, it shows interaction with P-glycoprotein (P-gp) inhibitors, but is the only factor Xa inhibitor not contraindicated in co-medication with strong inhibitors of both CYP3A4 and P-glycoprotein, such as dronedarone (Table 1 ) [ 99 ]. Excretion is 50% renal leading to a recommended dose reduction to 30 mg daily in patients with renal impairment (Table 1 ) [ 97 ]. The pivotal, randomized, phase III clinical trial to evaluate edoxaban, ENGAGE AF-TIMI 48 (The Effective Anticoagulation with Factor Xa Next Generation in AF–Thrombolysis in Myocardial Infarction 48), compared two different doses of edoxaban (30 and 60 mg) to warfarin [ 100 ].…”