Edoxaban

Identification

Summary

Edoxaban is a novel oral anticoagulant used for reducing the risk of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (NVAF).

Brand Names

Lixiana, Savaysa

Generic Name

Edoxaban

DrugBank Accession Number

DB09075

Background

Edoxaban is a member of the Novel Oral Anti-Coagulants (NOACs) class of drugs, and is a rapidly acting, oral, selective factor Xa inhibitor. By inhibiting factor Xa, a key protein in the coagulation cascade, edoxaban prevents the stepwise amplification of protein factors needed to form blood clots. It is indicated to reduce the risk of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (NVAF) and for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5-10 days of initial therapy with a parenteral anticoagulant. Traditionally, warfarin, a vitamin K antagonist, was used for stroke prevention in these individuals but effective use of this drug is limited by it's delayed onset, narrow therapeutic window, need for regular monitoring and INR testing, and numerous drug-drug and drug-food interactions. This has prompted enthusiasm for newer agents such as dabigatran, apixaban, and rivaroxaban for effective clot prevention. In addition to once daily dosing, the benefits over warfarin also include significant reductions in hemorrhagic stroke and GI bleeding, and improved compliance, which is beneficial as many patients will be on lifelong therapy.

Type

Small Molecule

Groups

Approved

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Edoxaban (DB09075)

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Weight

Average: 548.06
Monoisotopic: 547.1768513

Chemical Formula

C₂₄H₃₀ClN₇O₄S

Synonyms

• Edoxaban

External IDs

• DU 176
• DU 176b
• DU-176
• DU-176b

Pharmacology

Indication

Edoxaban is indicated for reducing the risk of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (NVAF). However, it should not be used in patients with creatinine clearance (CrCL) > 95 mL/min because of increased risk of ischemic stroke compared to warfarin at the highest dose studied (60 mg). It is also indicated for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5-10 days of initial therapy with a parenteral anticoagulant.

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Associated Conditions

• Deep Vein Thrombosis
• Pulmonary Embolism
• Stroke
• Systemic Embolism

Contraindications & Blackbox Warnings

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Pharmacodynamics

Administration of edoxaban results in prolongation of clotting time tests such as aPTT (activated partial thromboplastin time), PT (prothrombin time), and INR (international normalized ratio).

Mechanism of action

Edoxaban is a selective inhibitor of factor Xa, a serine endopeptidase of the clotting cascade required for cleavage of prothrombin into thrombin.

Target	Actions	Organism
ACoagulation factor X	inhibitor	Humans

Absorption

Following oral administration, peak plasma edoxaban concentrations are observed within 1-2 hours. Absolute bioavailability is 62%.

Volume of distribution

The steady state volume of distribution is 107 L.

Protein binding

In vitro plasma protein binding is ~55%.

Metabolism

Edoxaban is not extensively metabolized by CYP3A4 resulting in minimal drug-drug interactions. However, it does interact with drugs that inhibit p-gp (p-glycoprotein), which is used to transport edoxaban across the intestinal wall. Unchanged edoxaban is the predominant form in plasma. There is minimal metabolism via hydrolysis (mediated by carboxylesterase 1), conjugation, and oxidation by CYP3A4. The predominant metabolite M-4, formed by hydrolysis, is human-specific and active and reaches less than 10% of the exposure of the parent compound in healthy subjects. Exposure to the other metabolites is less than 5% of exposure to edoxaban.

Route of elimination

Edoxaban is eliminated primarily as unchanged drug in urine. Renal clearance (11 L/hour) accounts for approximately 50% of the total clearance of edoxaban (22 L/hour). Metabolism and biliary/intestinal excretion account for the remaining clearance.

Half-life

The terminal elimination half-life of edoxaban following oral administration is 10 to 14 hours.

Clearance

22 L/hr

Adverse Effects

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Toxicity

Premature discontinuation of any oral anticoagulant, including edoxaban, in the absence of adequate alternative anticoagulation increases the risk of ischemic events. If edoxaban is discontinued for reasons other than pathological bleeding or completion of a course of therapy, consider the use of another anticoagulant. Edoxaban increases the risk of potentially fatal major bleeding such as intracranial hemorrhage and gastrointestinal bleeding. Patients should be educated on how to watch for signs of major and minor bleeding and when to seek medical help. Co-administration of other anti-coagulants, anti-platelets, or thrombolytics may increase the risk of bleeding and should therefore be avoided.

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abacavir	Abacavir may decrease the excretion rate of Edoxaban which could result in a higher serum level.
Abciximab	The risk or severity of bleeding can be increased when Edoxaban is combined with Abciximab.
Abemaciclib	The serum concentration of Abemaciclib can be increased when it is combined with Edoxaban.
Abrocitinib	The serum concentration of Edoxaban can be increased when it is combined with Abrocitinib.
Aceclofenac	The risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Edoxaban.
Acemetacin	The risk or severity of bleeding and hemorrhage can be increased when Edoxaban is combined with Acemetacin.
Acenocoumarol	The risk or severity of bleeding can be increased when Edoxaban is combined with Acenocoumarol.
Acetaminophen	Acetaminophen may decrease the excretion rate of Edoxaban which could result in a higher serum level.
Acetazolamide	Acetazolamide may increase the excretion rate of Edoxaban which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acid	Acetylsalicylic acid may increase the anticoagulant activities of Edoxaban.

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Food Interactions

• Avoid herbs and supplements with anticoagulant/antiplatelet activity. Additive anticoagulant activity may increase the risk of bleeding. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
• Take with or without food.

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Edoxaban tosylate	32W99UE810	480449-71-6	ZLFZITWZOYXXAW-QXXZOGQOSA-N
Edoxaban tosylate monohydrate	972203R4EW	1229194-11-9	PSMMNJNZVZZNOI-SJILXJHISA-N

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Lixiana	Tablet, film coated	60 mg	Oral	Daiichi Sankyo Europe, Gmb H	2016-09-08	Not applicable
Lixiana	Tablet, film coated	60 mg	Oral	Daiichi Sankyo Europe, Gmb H	2016-09-08	Not applicable
Lixiana	Tablet, film coated	30 mg	Oral	Daiichi Sankyo Europe, Gmb H	2016-09-08	Not applicable
Lixiana	Tablet, film coated	60 mg	Oral	Daiichi Sankyo Europe, Gmb H	2016-09-08	Not applicable
Lixiana	Tablet	60 mg	Oral	Servier	2017-04-25	Not applicable
Lixiana	Tablet, film coated	60 mg	Oral	Daiichi Sankyo Europe, Gmb H	2016-09-08	Not applicable
Lixiana	Tablet, film coated	30 mg	Oral	Daiichi Sankyo Europe, Gmb H	2016-09-08	Not applicable
Lixiana	Tablet, film coated	15 mg	Oral	Daiichi Sankyo Europe, Gmb H	2016-09-08	Not applicable
Lixiana	Tablet, film coated	60 mg	Oral	Daiichi Sankyo Europe, Gmb H	2016-09-08	Not applicable
Lixiana	Tablet, film coated	30 mg	Oral	Daiichi Sankyo Europe, Gmb H	2016-09-08	Not applicable

Categories

ATC Codes

B01AF03 — Edoxaban

• B01AF — Direct factor Xa inhibitors
• B01A — ANTITHROMBOTIC AGENTS
• B01 — ANTITHROMBOTIC AGENTS
• B — BLOOD AND BLOOD FORMING ORGANS

Drug Categories

• Anticoagulants
• Antithrombins
• Blood and Blood Forming Organs
• Direct factor Xa inhibitors
• Drugs that are Mainly Renally Excreted
• Enzyme Inhibitors
• Factor Xa Inhibitors
• Hematologic Agents
• P-glycoprotein substrates
• Protease Inhibitors
• Serine Protease Inhibitors
• Sulfur Compounds

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Gamma amino acids and derivatives

Alternative Parents

Alpha amino acid amides / 2-heteroaryl carboxamides / Thiazolecarboxamides / N-arylamides / Aralkylamines / Aryl chlorides / Imidolactams / Pyridines and derivatives / Tertiary carboxylic acid amides / Heteroaromatic compounds / Secondary carboxylic acid amides / Trialkylamines / Azacyclic compounds / Hydrocarbon derivatives / Carbonyl compounds / Organic oxides / Organochlorides / Organopnictogen compounds

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Substituents

2-heteroaryl carboxamide / Alpha-amino acid amide / Alpha-amino acid or derivatives / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Azole / Carbonyl group / Carboxamide group / Gamma amino acid or derivatives / Heteroaromatic compound / Hydrocarbon derivative / Imidolactam / N-arylamide / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organochloride / Organohalogen compound / Organoheterocyclic compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Pyridine / Secondary carboxylic acid amide / Tertiary aliphatic amine / Tertiary amine / Tertiary carboxylic acid amide / Thiazole / Thiazolecarboxamide / Thiazolecarboxylic acid or derivatives

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Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

tertiary amino compound, monocarboxylic acid amide, chloropyridine, thiazolopyridine (CHEBI:85973)

Affected organisms

Not Available

Chemical Identifiers

UNII

NDU3J18APO

CAS number

480449-70-5

InChI Key

HGVDHZBSSITLCT-JLJPHGGASA-N

InChI

InChI=1S/C24H30ClN7O4S/c1-31(2)24(36)13-4-6-15(27-20(33)21(34)30-19-7-5-14(25)11-26-19)17(10-13)28-22(35)23-29-16-8-9-32(3)12-18(16)37-23/h5,7,11,13,15,17H,4,6,8-10,12H2,1-3H3,(H,27,33)(H,28,35)(H,26,30,34)/t13-,15-,17+/m0/s1

IUPAC Name

N'-(5-chloropyridin-2-yl)-N-[(1S,2R,4S)-4-(dimethylcarbamoyl)-2-{5-methyl-4H,5H,6H,7H-[1,3]thiazolo[5,4-c]pyridine-2-amido}cyclohexyl]ethanediamide

SMILES

CN(C)C(=O)[C@H]1CC[C@H](NC(=O)C(=O)NC2=NC=C(Cl)C=C2)[C@@H](C1)NC(=O)C1=NC2=C(CN(C)CC2)S1

References

General References

1. Turpie AG: New oral anticoagulants in atrial fibrillation. Eur Heart J. 2008 Jan;29(2):155-65. Epub 2007 Dec 19. [Article]
2. Ogata K, Mendell-Harary J, Tachibana M, Masumoto H, Oguma T, Kojima M, Kunitada S: Clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel factor Xa inhibitor edoxaban in healthy volunteers. J Clin Pharmacol. 2010 Jul;50(7):743-53. doi: 10.1177/0091270009351883. Epub 2010 Jan 15. [Article]
3. Yeh CH, Hogg K, Weitz JI: Overview of the new oral anticoagulants: opportunities and challenges. Arterioscler Thromb Vasc Biol. 2015 May;35(5):1056-65. doi: 10.1161/ATVBAHA.115.303397. Epub 2015 Mar 19. [Article]
4. Senoo K, Lip GY: Comparative efficacy and safety of the non-vitamin K antagonist oral anticoagulants for patients with nonvalvular atrial fibrillation. Semin Thromb Hemost. 2015 Mar;41(2):146-53. doi: 10.1055/s-0035-1544156. Epub 2015 Feb 15. [Article]
5. Parasrampuria DA, Truitt KE: Pharmacokinetics and Pharmacodynamics of Edoxaban, a Non-Vitamin K Antagonist Oral Anticoagulant that Inhibits Clotting Factor Xa. Clin Pharmacokinet. 2015 Nov 30. [Article]
6. FDA Approved Drug Products: Savaysa (edoxaban tosylate) tablets for oral use [Link]

External Links

KEGG Drug

D09546

PubChem Compound

10280735

PubChem Substance

310265005

ChemSpider

8456212

BindingDB

50328731

RxNav

1599538

ChEBI

85973

ChEMBL

CHEMBL1269025

ZINC

ZINC000043200832

PharmGKB

PA166128806

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Edoxaban

FDA label

Download (600 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Treatment	Atrial Fibrillation / Chronic Stable Angina Pectoris / Coronary Artery Disease (CAD) / Stable Angina (SA)	1
4	Completed	Basic Science	Coagulation Disorder	1
4	Completed	Prevention	Premature Ventricular Contraction (PVC) / Stroke / Ventricular Tachycardia (VT)	1
4	Completed	Treatment	Anticoagulant Therapy / Neoplasm / Venous Thrombosis (Disorder)	1
4	Completed	Treatment	Cancer / Thromboembolism	1
4	Completed	Treatment	Coronary Artery Disease (CAD)	1
4	Completed	Treatment	Diabetes	1
4	Recruiting	Other	Non-valvular Atrial Fibrillation	1
4	Recruiting	Prevention	Atrial Fibrillation	2
4	Recruiting	Prevention	Atrial Fibrillation / Atrial Flutter	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Tablet	Oral	15 mg
Tablet	Oral	20.210 mg
Tablet	Oral	30 mg
Tablet	Oral	60 mg
Tablet, film coated	Oral
Tablet, coated	Oral	15 mg
Tablet, coated	Oral	30 mg
Tablet, coated	Oral	60 mg
Tablet, film coated	Oral	15 mg
Tablet, film coated	Oral	30 mg
Tablet, film coated	Oral	60 mg
Tablet, film coated	Oral	15 mg/1
Tablet, film coated	Oral	30 mg/1
Tablet, film coated	Oral	60 mg/1

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US2013026553	No	2011-08-22	2031-08-22
US9149532	No	2015-10-06	2028-03-28
US7365205	No	2008-04-29	2023-06-12

Properties

State

Solid

Experimental Properties

Property	Value	Source
pKa	6.7	FDA Label

Predicted Properties

Property	Value	Source
Water Solubility	0.0114 mg/mL	ALOGPS
logP	1.61	ALOGPS
logP	0.9	Chemaxon
logS	-4.7	ALOGPS
pKa (Strongest Acidic)	10.74	Chemaxon
pKa (Strongest Basic)	6.33	Chemaxon
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	7	Chemaxon
Hydrogen Donor Count	3	Chemaxon
Polar Surface Area	136.63 Å2	Chemaxon
Rotatable Bond Count	6	Chemaxon
Refractivity	140.14 m3·mol-1	Chemaxon
Polarizability	56.31 Å3	Chemaxon
Number of Rings	4	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	No	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	Yes	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Targets

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Details1. Coagulation factor X

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Inhibitor

General Function

Serine-type endopeptidase activity

Specific Function

Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.

Gene Name

F10

Uniprot ID

P00742

Uniprot Name

Coagulation factor X

Molecular Weight

54731.255 Da

References

1. Turpie AG: New oral anticoagulants in atrial fibrillation. Eur Heart J. 2008 Jan;29(2):155-65. Epub 2007 Dec 19. [Article]

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Drug created at May 15, 2015 16:35 / Updated at December 06, 2023 02:33