Edoxaban is an oral anticoagulant. It belongs to the drug class: direct oral anticoagulants (DOAC) and the subclass: Xa inhibitor.
Mechanism of Action
Edoxaban works by interrupting the sequence of clotting factor activations in the common pathway of the coagulation cascade via factor Xa. This halts thrombin activation and the conversion of fibrin to fibrinogen.
If you have any questions about the process of hemostasis and the coagulation cascade the unit What You Need to Know: Hemostasis provides an excellent overview.
Indications
Edoxaban is indicated for use in:
- atrial fibrillation/flutter
- venous thromboembolism.
The ENGAGE Trial
The ENGAGE trial compared edoxaban to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation.
Efficacy was determined by the rate occurrence of stroke and systemic embolism in each group.
Safety was determined by the rate of major bleed in each group.
Edoxaban was found to be non inferior to warfarin in preventing stroke or systemic embolism and caused less bleeding.
Administration & Availability
Edoxaban is available as an oral tablet. For patients who are unable to swallow whole tablets, edoxaban tablets may be crushed and mixed with 60 to 90ml of water and immediately administered by mouth or through a gastric tube.
The crushed tablets may also be mixed into applesauce and immediately administered orally.
Edoxaban can be given without regard to meals.
Missed Dose
If a dose of edoxaban is missed, the dose should be taken as soon as possible on the same day. Dosing should resume the next day according to the normal dosing schedule.
Dosing
Edoxaban is dosed at 60 mg once daily in patients with CrCL >50 to ≤ 95 mL/min.
Edoxaban is unique among the Xa inhibitors in that it cannot be used in patients with a high creatinine clearance (>95ml/min).
At high renal clearance there is an increased risk of ischemic stroke compared to warfarin.
Reduce dose to 30 mg once daily in patients with creatinine clearance 15 to 50 mL/min.
Avoid use with CrCl<15ml/min and in hemodialysis.
Drug Interactions
With edoxaban the interaction with P-gp transporters is more significant than CYP enzymes. There is minimal engagement with cytochrome enzymes but it is a substrate of P-gp transporters.
The only P-gp inducer that is listed as a significant interaction with edoxaban is rifampin. It is recommended to avoid edoxaban and rifampin coadministration because of decreased serum concentration and risk of thromboembolic events.
For all other clinically relevant P-gp inducers the recommendation is to monitor therapy or consider alternate therapies.
No dose reduction is recommended for concomitant P-gp inhibitor use. Clinical experience from the ENGAGE trial showed dose reduction in patients concomitantly receiving P-gp inhibitors resulted in edoxaban blood levels that were lower than in patients who were given the full dose.
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