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Identification
NameEdoxaban
Accession NumberDB09075
TypeSmall Molecule
GroupsApproved
Description

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.

Structure
Thumb
SynonymsNot Available
External Identifiers
  • DU 176
  • DU 176b
  • DU-176
  • DU-176b
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Savaysatablet, film coated15 mg/1oralDaiichi Sankyo, Inc.2015-01-12Not applicableUs
Savaysatablet, film coated60 mg/1oralDaiichi Sankyo, Inc.2015-01-12Not applicableUs
Savaysatablet, film coated30 mg/1oralDaiichi Sankyo, Inc.2015-01-12Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
LixianaDaiichi-Sankyo
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Edoxaban tosylate
480449-71-6
ThumbNot applicableDBSALT001717
Edoxaban tosylate monohydrate
1229194-11-9
ThumbNot applicableDBSALT001718
CategoriesNot Available
UNIINDU3J18APO
CAS number480449-70-5
WeightAverage: 548.06
Monoisotopic: 547.1768513
Chemical FormulaC24H30ClN7O4S
InChI KeyHGVDHZBSSITLCT-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)[[email protected]]1CC[[email protected]](NC(=O)C(=O)NC2=NC=C(Cl)C=C2)[C@@H](C1)NC(=O)C1=NC2=C(CN(C)CC2)S1
Taxonomy
ClassificationNot classified
Pharmacology
IndicationEdoxaban is indicated to reduce 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.
PharmacodynamicsAdministration 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 actionEdoxaban is a selective inhibitor of factor Xa, a serine endopeptidase of the clotting cascade required for cleavage of prothrombin into thrombin.
Related Articles
AbsorptionFollowing 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 bindingIn 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 eliminationEdoxaban 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 lifeThe terminal elimination half-life of edoxaban following oral administration is 10 to 14 hours.
Clearance

22 L/hr

ToxicityPremature 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.
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 inhibitorNot AvailableNot Available
CYP450 2D6 inhibitorNot AvailableNot Available
CYP450 2C19 inhibitorNot AvailableNot Available
CYP450 3A4 inhibitorNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tablet, film coatedoral15 mg/1
Tablet, film coatedoral30 mg/1
Tablet, film coatedoral60 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US2013026553 No2011-08-222031-08-22Us
US7365205 No2003-06-122023-06-12Us
US9149532 No2008-03-282028-03-28Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
pKa6.7FDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.0114 mg/mLALOGPS
logP1.61ALOGPS
logP0.9ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)10.74ChemAxon
pKa (Strongest Basic)6.33ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area136.63 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity140.14 m3·mol-1ChemAxon
Polarizability56.31 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Turpie AG: New oral anticoagulants in atrial fibrillation. Eur Heart J. 2008 Jan;29(2):155-65. Epub 2007 Dec 19. [PubMed:18096568 ]
  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. [PubMed:20081065 ]
  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. [PubMed:25792448 ]
  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. [PubMed:25682085 ]
  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. [PubMed:26620048 ]
External Links
ATC CodesNot Available
AHFS Codes
  • 20:12.04.14
PDB EntriesNot Available
FDA labelDownload (600 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbciximabEdoxaban may increase the anticoagulant activities of Abciximab.
AbirateroneThe serum concentration of Edoxaban can be increased when it is combined with Abiraterone.
AcenocoumarolEdoxaban may increase the anticoagulant activities of Acenocoumarol.
Acetylsalicylic acidAcetylsalicylic acid may increase the anticoagulant activities of Edoxaban.
AlteplaseAlteplase may increase the anticoagulant activities of Edoxaban.
AmiodaroneThe serum concentration of Edoxaban can be increased when it is combined with Amiodarone.
AnistreplaseAnistreplase may increase the anticoagulant activities of Edoxaban.
ApixabanEdoxaban may increase the anticoagulant activities of Apixaban.
ArgatrobanEdoxaban may increase the anticoagulant activities of Argatroban.
AtorvastatinThe serum concentration of Edoxaban can be increased when it is combined with Atorvastatin.
AzithromycinThe serum concentration of Edoxaban can be increased when it is combined with Azithromycin.
BivalirudinEdoxaban may increase the anticoagulant activities of Bivalirudin.
CarvedilolThe serum concentration of Edoxaban can be increased when it is combined with Carvedilol.
ChlorotrianiseneChlorotrianisene may decrease the anticoagulant activities of Edoxaban.
Citric AcidEdoxaban may increase the anticoagulant activities of Citric Acid.
ClarithromycinThe serum concentration of Edoxaban can be increased when it is combined with Clarithromycin.
CobicistatThe serum concentration of Edoxaban can be increased when it is combined with Cobicistat.
CollagenaseThe risk or severity of adverse effects can be increased when Edoxaban is combined with Collagenase.
CrizotinibThe serum concentration of Edoxaban can be increased when it is combined with Crizotinib.
CyclosporineThe serum concentration of Edoxaban can be increased when it is combined with Cyclosporine.
Dabigatran etexilateEdoxaban may increase the anticoagulant activities of Dabigatran etexilate.
DaclatasvirThe serum concentration of Edoxaban can be increased when it is combined with Daclatasvir.
DalteparinEdoxaban may increase the anticoagulant activities of Dalteparin.
DanaparoidEdoxaban may increase the anticoagulant activities of Danaparoid.
DarunavirThe serum concentration of Edoxaban can be increased when it is combined with Darunavir.
DasatinibDasatinib may increase the anticoagulant activities of Edoxaban.
DeferasiroxThe risk or severity of adverse effects can be increased when Edoxaban is combined with Deferasirox.
Deoxycholic AcidThe risk or severity of adverse effects can be increased when Edoxaban is combined with Deoxycholic Acid.
DesirudinEdoxaban may increase the anticoagulant activities of Desirudin.
DesogestrelThe therapeutic efficacy of Edoxaban can be decreased when used in combination with Desogestrel.
DicoumarolEdoxaban may increase the anticoagulant activities of Dicoumarol.
DipyridamoleThe serum concentration of Edoxaban can be increased when it is combined with Dipyridamole.
DronedaroneThe serum concentration of Edoxaban can be increased when it is combined with Dronedarone.
DydrogesteroneThe therapeutic efficacy of Edoxaban can be decreased when used in combination with Dydrogesterone.
Edetic AcidEdoxaban may increase the anticoagulant activities of Edetic Acid.
EliglustatThe serum concentration of Edoxaban can be increased when it is combined with Eliglustat.
EnoxaparinEdoxaban may increase the anticoagulant activities of Enoxaparin.
ErythromycinThe serum concentration of Edoxaban can be increased when it is combined with Erythromycin.
Ethyl biscoumacetateEdoxaban may increase the anticoagulant activities of Ethyl biscoumacetate.
FlibanserinThe serum concentration of Edoxaban can be increased when it is combined with Flibanserin.
Fondaparinux sodiumEdoxaban may increase the anticoagulant activities of Fondaparinux sodium.
GestodeneThe therapeutic efficacy of Edoxaban can be decreased when used in combination with Gestodene.
HeparinEdoxaban may increase the anticoagulant activities of Heparin.
HomoharringtonineThe risk or severity of adverse effects can be increased when Edoxaban is combined with Homoharringtonine.
Ibritumomab tiuxetanThe risk or severity of adverse effects can be increased when Edoxaban is combined with Ibritumomab.
IbrutinibThe serum concentration of Edoxaban can be increased when it is combined with Ibrutinib.
InfliximabInfliximab may increase the anticoagulant activities of Edoxaban.
ItraconazoleThe serum concentration of Edoxaban can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Edoxaban can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Edoxaban can be increased when it is combined with Ketoconazole.
LapatinibThe serum concentration of Edoxaban can be increased when it is combined with Lapatinib.
LimaprostThe risk or severity of adverse effects can be increased when Limaprost is combined with Edoxaban.
LomitapideThe serum concentration of Edoxaban can be increased when it is combined with Lomitapide.
LumacaftorThe serum concentration of Edoxaban can be decreased when it is combined with Lumacaftor.
MefloquineThe serum concentration of Edoxaban can be increased when it is combined with Mefloquine.
MirabegronThe serum concentration of Edoxaban can be increased when it is combined with Mirabegron.
NadroparinEdoxaban may increase the anticoagulant activities of Nadroparin.
NicardipineThe serum concentration of Edoxaban can be increased when it is combined with Nicardipine.
NilotinibThe serum concentration of Edoxaban can be increased when it is combined with Nilotinib.
NintedanibThe risk or severity of adverse effects can be increased when Edoxaban is combined with Nintedanib.
ObinutuzumabThe risk or severity of adverse effects can be increased when Edoxaban is combined with Obinutuzumab.
Omega-3 fatty acidsOmega-3 fatty acids may increase the anticoagulant activities of Edoxaban.
Pentosan PolysulfatePentosan Polysulfate may increase the anticoagulant activities of Edoxaban.
PhenindioneEdoxaban may increase the anticoagulant activities of Phenindione.
PhenprocoumonEdoxaban may increase the anticoagulant activities of Phenprocoumon.
ProgesteroneThe serum concentration of Edoxaban can be increased when it is combined with Progesterone.
PropranololThe serum concentration of Edoxaban can be increased when it is combined with Propranolol.
QuinidineThe serum concentration of Edoxaban can be increased when it is combined with Quinidine.
QuinineThe serum concentration of Edoxaban can be increased when it is combined with Quinine.
RanolazineThe serum concentration of Edoxaban can be increased when it is combined with Ranolazine.
ReserpineThe serum concentration of Edoxaban can be increased when it is combined with Reserpine.
ReteplaseReteplase may increase the anticoagulant activities of Edoxaban.
RidogrelRidogrel may increase the anticoagulant activities of Edoxaban.
RifampicinThe serum concentration of Edoxaban can be decreased when it is combined with Rifampicin.
RitonavirThe serum concentration of Edoxaban can be increased when it is combined with Ritonavir.
RivaroxabanEdoxaban may increase the anticoagulant activities of Rivaroxaban.
RolapitantThe serum concentration of Edoxaban can be increased when it is combined with Rolapitant.
SaquinavirThe serum concentration of Edoxaban can be increased when it is combined with Saquinavir.
SimeprevirThe serum concentration of Edoxaban can be increased when it is combined with Simeprevir.
StreptokinaseStreptokinase may increase the anticoagulant activities of Edoxaban.
SugammadexSugammadex may increase the anticoagulant activities of Edoxaban.
SulodexideEdoxaban may increase the anticoagulant activities of Sulodexide.
SunitinibThe serum concentration of Edoxaban can be increased when it is combined with Sunitinib.
TacrolimusThe serum concentration of Edoxaban can be increased when it is combined with Tacrolimus.
TamoxifenThe serum concentration of Edoxaban can be increased when it is combined with Tamoxifen.
TelaprevirThe serum concentration of Edoxaban can be increased when it is combined with Telaprevir.
TenecteplaseTenecteplase may increase the anticoagulant activities of Edoxaban.
TesmilifeneThe serum concentration of Edoxaban can be decreased when it is combined with Tesmilifene.
TiboloneTibolone may increase the anticoagulant activities of Edoxaban.
TinzaparinEdoxaban may increase the anticoagulant activities of Tinzaparin.
TipranavirTipranavir may increase the anticoagulant activities of Edoxaban.
TositumomabThe risk or severity of adverse effects can be increased when Edoxaban is combined with Tositumomab.
TreprostinilEdoxaban may increase the anticoagulant activities of Treprostinil.
UrokinaseUrokinase may increase the anticoagulant activities of Edoxaban.
VandetanibThe serum concentration of Edoxaban can be increased when it is combined with Vandetanib.
VemurafenibThe serum concentration of Edoxaban can be increased when it is combined with Vemurafenib.
VerapamilThe serum concentration of Edoxaban can be increased when it is combined with Verapamil.
Vitamin EVitamin E may increase the anticoagulant activities of Edoxaban.
VorapaxarThe risk or severity of adverse effects can be increased when Vorapaxar is combined with Edoxaban.
WarfarinEdoxaban may increase the anticoagulant activities of Warfarin.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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
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. [PubMed:18096568 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
References
  1. Mikkaichi T, Yoshigae Y, Masumoto H, Imaoka T, Rozehnal V, Fischer T, Okudaira N, Izumi T: Edoxaban transport via P-glycoprotein is a key factor for the drug's disposition. Drug Metab Dispos. 2014 Apr;42(4):520-8. doi: 10.1124/dmd.113.054866. Epub 2014 Jan 23. [PubMed:24459178 ]
Comments
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Drug created on May 15, 2015 10:35 / Updated on May 29, 2016 02:12