Edoxaban is an oral anticoagulant that inhibits Factor Xa to prevent thrombin formation. It is FDA-approved to reduce the risk of stroke in nonvalvular atrial fibrillation and to treat DVT and PE. Two major clinical trials found Edoxaban non-inferior to warfarin for these indications and with less major bleeding risk. Edoxaban has contraindications for active bleeding and warnings for serious bleeding risk and should not be used with mechanical heart valves or moderate to severe mitral stenosis.

1. Marion General Hospital Formulary Evaluation
Monograph
Generic Name (Trade Name): Edoxaban (Savaysa)
Manufacturer: Daiichi Sankyo, Inc
Dosage Forms (NDC #): oral tablet
AHFS Class: Anticoagulant
Storage: 20-25°C
Description and Pharmacology: Edoxaban is an oral anticoagulant that inhibits Factor Xa to prevent the formation of
thrombin.
Pharmacokinetics
• See supplementary handout
FDA-Approved Indications1
• Reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.
• Treatment of DVT and PE 5-10 days after initial therapy with a parenteral anticoagulant
Clinical Trials
Title ENGAGE AF-TIMI 48 Study
Objective Comapre efficacy and safety of two dosing regimens of Edoxaban compared to
warfarin in reducing risk of stroke or systemic embolism in patients with non-valvular
A.Fib.
Design Multi-national, double blind, non-inferiority study
21,105 patients
Follow up: 2.8 years
Methods Treatment arms: Edoxaban 60mg or 30mg vs. warfarin adjusted to a target INR of
2-3
Primary endpoint: occurrence of first stroke or systemic embolism, p<0.001
Safety outcome: major bleeding
Results Warfarin vs. Edoxaban 60mg vs. Edoxaban 30mg
Event rate per year of stroke or systemic embolism: 232 pts vs.182pts p<0.001.
vs. 253 pts p=0.005
Annual rate of major bleeding: 3.75% vs. 2.75%p<0.001 vs. 1.61% p<0.001
Conclusions Edoxaban 60 mg showed non-inferiority to warfarin for prevention of stroke or
systemic embolism as well as ischemic stroke alone. Edoxaban 30mg showed non-
inferiority to warfarin in the primary outcome however risk of ischemic stroke
increased. Both doses showed decrease in rates of hemorrhagic stroke, major
bleeding, intracranial bleeding, and life-threatening bleeding. GI bleeding occurred
more commonly with Edoxaban 60mg.
Comments
Title Hokusai VTE Study

2. Objective Compare efficacy and safety of edoxaban in the treatment of DVT/PE compared to
standard treatment with warfarin.
Design Randomized, double-blind, non-inferiority trial
8,292 patients
Methods Treatment arms: Edoxaban 60mg + parenteral anticoagulant(30mg if qualified for
reduced dosage) vs. warfarin titrated to target INR of 2-3 + parenteral anticoagulant
Primary outcome: incidence of symptomatic recurrent VTE which s defined as a
composite of DVT or nonfatal/fatal PE.
Safety outcome: major or clinically relevant nonmajor bleeding
Results Edoxaban vs. Warfarin
Recurrent VTE: 130/4118 pts (3.2%) vs. 146/4122 pts (3.5%) HR: 0.89; 95% CI:
0.70 to 1.13; P<0.001
Clinically relevant bleeding: 349/4118pts (8.5%) vs. 423/4122pts (10.3%), HR: 0.81;
95% CI, 0.71 to 0.94; P=0.004
Conclusions Edoxaban in the treatment of VTE was non-inferior to warfarin in the prevention of
recurrent VTE and superior to warfarin in regards to bleeding.
Comments
Safety and Tolerability
Contraindications: Active pathological bleeding
Warnings and Precautions:
• Serious and fatal bleeding can occur
• Use is not recommended in patients with mechanical heart valves or moderate to severe mitral stenosis
.
Adverse Drug Effects
• See supplementary material
Drug Interactions
• Anticoagulants, antiplatelet, and thrombolytics: increase risk of bleeding
• Pgp inducers: Avoid co-administration with rifampin
• Pgp inhibitors: Dose should be adjusted with concurrent use of verapamil, quinidine, or dronedarone . In general, other
Pgp inhibitors do not require dose adjustments.
Medication Error Possibility
• CrCL cutoff for treatment of A.fib and not for treatment of DVT/PE
Dosing and Administration
• See supplementary handout

3. References:
1. Edoxaban [Package Insert]. Tokyo: Daiichi Sankyo, Inc; 2015.
2. Giugliano RP. Effective anticoagulation with factor Xa next generation in atrial fibrillation-TIMI 48. Powerpoint
presentation: http://my.americanheart.org/idc/groups/ahamah-
public/@wcm/@sop/@scon/documents/downloadable/ucm_458280.pdf. Accessed April 21, 2015.