U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C19H15O4.K
Molecular Weight 346.4183
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of WARFARIN POTASSIUM

SMILES

[K+].CC(=O)CC(C1=CC=CC=C1)C2=C([O-])C3=CC=CC=C3OC2=O

InChI

InChIKey=WSHYKIAQCMIPTB-UHFFFAOYSA-M
InChI=1S/C19H16O4.K/c1-12(20)11-15(13-7-3-2-4-8-13)17-18(21)14-9-5-6-10-16(14)23-19(17)22;/h2-10,15,21H,11H2,1H3;/q;+1/p-1

HIDE SMILES / InChI

Molecular Formula C19H15O4
Molecular Weight 307.32
Charge -1
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Molecular Formula K
Molecular Weight 39.0983
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Warfarin is an anticoagulant drug normally used to prevent blood clot formation as well as migration. Warfarin is marketed under the brand name Coumadin among others. Coumadin (crystalline warfarin sodium) is an anticoagulant which acts by inhibiting vitamin K-dependent coagulation factors. Chemically, it is 3-(α-acetonylbenzyl)-4-hydroxycoumarin and is a racemic mixture of the R- and S-enantiomers. Coumadin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. It is also indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of the vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K1 epoxide. The degree of depression is dependent upon the dosage administered and, in part, by the patient’s VKORC1 genotype. Therapeutic doses of warfarin decrease the total amount of the active form of each vitamin K dependent clotting factor made by the liver by approximately 30% to 50%.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
COUMADIN

Approved Use

Warfarin sodium tablets are indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. Warfarin sodium tablets are indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. Warfarin sodium tablets are indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction.

Launch Date

1954
Preventing
COUMADIN

Approved Use

Warfarin sodium tablets are indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. Warfarin sodium tablets are indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. Warfarin sodium tablets are indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction.

Launch Date

1954
Preventing
COUMADIN

Approved Use

Warfarin sodium tablets are indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. Warfarin sodium tablets are indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. Warfarin sodium tablets are indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction.

Launch Date

1954
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2186 ng/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
WARFARIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
52278 ng × h/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
WARFARIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
32.4 h
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
WARFARIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
7 day
single, oral
WARFARIN unknown
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
single, oral
WARFARIN unknown
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
125 mg single, oral
Overdose
Dose: 125 mg
Route: oral
Route: single
Dose: 125 mg
Co-administed with::
oxycodone, p.o(200 mg, single)
Sources: Page: p.718
unhealthy, 43
n = 1
Health Status: unhealthy
Condition: Deep venous thromboses
Age Group: 43
Sex: M
Population Size: 1
Sources: Page: p.718
Disc. AE: Vomiting, Loss of consciousness...
AEs leading to
discontinuation/dose reduction:
Vomiting
Loss of consciousness
Sources: Page: p.718
150 mg single, oral
Overdose
Dose: 150 mg
Route: oral
Route: single
Dose: 150 mg
Co-administed with::
chlorpromazine, p.o(3 g, single)
Sources: Page: p.718
unhealthy, 44
n = 1
Health Status: unhealthy
Condition: Aortic valve replacement
Age Group: 44
Sex: M
Population Size: 1
Sources: Page: p.718
Disc. AE: Drowsiness...
AEs leading to
discontinuation/dose reduction:
Drowsiness
Sources: Page: p.718
540 mg single, oral
Overdose
Dose: 540 mg
Route: oral
Route: single
Dose: 540 mg
Co-administed with::
clonazepam, p.o(4 mg, single)
Sources: Page: p.1
healthy, 59
n = 1
Health Status: healthy
Age Group: 59
Sex: F
Population Size: 1
Sources: Page: p.1
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Sources: Page: p.1
unhealthy, 64
n = 1
Health Status: unhealthy
Condition: Cardiomyopathy |Atrial fibrillation
Age Group: 64
Sex: M
Population Size: 1
Sources: Page: p.1
Disc. AE: Hemoptysis, Hematuria...
AEs leading to
discontinuation/dose reduction:
Hemoptysis
Hematuria
Dyspnea
Cough
Sources: Page: p.1
10 mg 1 times / day multiple, oral (max)
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Venous thrombosis|Atrial fibrillation|Myocardial infarction
Sources: Page: p.1
Disc. AE: Bleeding...
AEs leading to
discontinuation/dose reduction:
Bleeding (grade 5)
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Loss of consciousness Disc. AE
125 mg single, oral
Overdose
Dose: 125 mg
Route: oral
Route: single
Dose: 125 mg
Co-administed with::
oxycodone, p.o(200 mg, single)
Sources: Page: p.718
unhealthy, 43
n = 1
Health Status: unhealthy
Condition: Deep venous thromboses
Age Group: 43
Sex: M
Population Size: 1
Sources: Page: p.718
Vomiting Disc. AE
125 mg single, oral
Overdose
Dose: 125 mg
Route: oral
Route: single
Dose: 125 mg
Co-administed with::
oxycodone, p.o(200 mg, single)
Sources: Page: p.718
unhealthy, 43
n = 1
Health Status: unhealthy
Condition: Deep venous thromboses
Age Group: 43
Sex: M
Population Size: 1
Sources: Page: p.718
Drowsiness Disc. AE
150 mg single, oral
Overdose
Dose: 150 mg
Route: oral
Route: single
Dose: 150 mg
Co-administed with::
chlorpromazine, p.o(3 g, single)
Sources: Page: p.718
unhealthy, 44
n = 1
Health Status: unhealthy
Condition: Aortic valve replacement
Age Group: 44
Sex: M
Population Size: 1
Sources: Page: p.718
Cough Disc. AE
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Sources: Page: p.1
unhealthy, 64
n = 1
Health Status: unhealthy
Condition: Cardiomyopathy |Atrial fibrillation
Age Group: 64
Sex: M
Population Size: 1
Sources: Page: p.1
Dyspnea Disc. AE
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Sources: Page: p.1
unhealthy, 64
n = 1
Health Status: unhealthy
Condition: Cardiomyopathy |Atrial fibrillation
Age Group: 64
Sex: M
Population Size: 1
Sources: Page: p.1
Hematuria Disc. AE
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Sources: Page: p.1
unhealthy, 64
n = 1
Health Status: unhealthy
Condition: Cardiomyopathy |Atrial fibrillation
Age Group: 64
Sex: M
Population Size: 1
Sources: Page: p.1
Hemoptysis Disc. AE
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Sources: Page: p.1
unhealthy, 64
n = 1
Health Status: unhealthy
Condition: Cardiomyopathy |Atrial fibrillation
Age Group: 64
Sex: M
Population Size: 1
Sources: Page: p.1
Bleeding grade 5
Disc. AE
10 mg 1 times / day multiple, oral (max)
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Venous thrombosis|Atrial fibrillation|Myocardial infarction
Sources: Page: p.1
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [Ki 8 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
yes
yes
likely (co-administration study)
Comment: Inhibitors of CYP2C9, 1A2, and/or 3A4 have the potential to increase the effect (increase INR) of warfarin by increasing the exposure of warfarin; Inducers of CYP2C9, 1A2, and/or 3A4 have the potential to decrease the effect (decrease INR) of warfarin by decreasing the exposure of warfarin
Page: 14.0
yes
likely (co-administration study)
Comment: Inhibitors of CYP2C9, 1A2, and/or 3A4 have the potential to increase the effect (increase INR) of warfarin by increasing the exposure of warfarin; Inducers of CYP2C9, 1A2, and/or 3A4 have the potential to decrease the effect (decrease INR) of warfarin by decreasing the exposure of warfarin
Page: 14.0
yes
yes (pharmacogenomic study)
Comment: If the patient’s CYP2C9 and/or VKORC1 genotype are known, consider these ranges in choosing the initial dose. Patients with CYP2C9 *1/*3, *2/*2, *2/*3, and *3/*3 may require more prolonged time (>2 to 4 weeks) to achieve maximum INR effect for a given dosage regimen than patients without these CYP variants; Inhibitors of CYP2C9, 1A2, and/or 3A4 have the potential to increase the effect (increase INR) of warfarin by increasing the exposure of warfarin; Inducers of CYP2C9, 1A2, and/or 3A4 have the potential to decrease the effect (decrease INR) of warfarin by decreasing the exposure of warfarin
Page: 14.0
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Prosthetic heart valve thrombosis during dicloxacillin therapy.
1999
Potentiation of anticoagulant effect of warfarin caused by enantioselective metabolic inhibition by the uricosuric agent benzbromarone.
1999 Dec
Anticoagulant induced submucosal hemorrhage mimicking a renal pelvic tumor.
2000 Jan
Coumarin derivatives and breast-feeding.
2000 Jun
Thrombolysis and antithrombotic therapy for coronary artery disease.
2001 Feb
Antithrombotic therapy in valvular heart disease.
2001 Feb
Oral anticoagulants. Pharmacologic issues for use in the elderly.
2001 Feb
Thrombus formation on atherosclerotic plaques: pathogenesis and clinical consequences.
2001 Feb 6
Cardiac and great vessel thrombosis in Behçet's disease.
2001 Jan
HIV and thrombosis: a review.
2001 Jan
Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves.
2001 Jan
Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range.
2001 Jan
Primary antiphospholipid syndrome masquerading as diabetic retinopathy.
2001 Jan-Feb
Sneddon's syndrome: a case report.
2001 Mar
Aspirin does not influence the effect of angiotensin-converting enzyme inhibition on left ventricular ejection fraction 3 months after acute myocardial infarction.
2001 Mar
Hemoptysis in patients with renal insufficiency : the role of flexible bronchoscopy.
2001 Mar
Mild head injury, anticoagulants, and risk of intracranial injury.
2001 Mar 10
Patents

Sample Use Guides

In Vivo Use Guide
Usual Adult Dose for Prevention of Thromboembolism in Atrial Fibrillation Initial dose: 2 to 5 mg orally once a day Maintenance dose: 2 to 10 mg orally once a day Usual Adult Dose for Myocardial Infarction Initial dose: 2 to 5 mg orally once a day Maintenance dose: 2 to 10 mg orally once a day Usual Adult Dose for Deep Vein Thrombosis - Prophylaxis Initial dose: 2 to 5 mg orally once a day Maintenance dose: 2 to 10 mg orally once a day
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: One strain (TAS) is susceptible and two strains (HW and HS) resistant to the anticoagulant and lethal effects of warfarin.
Vitamin K-reductase activity was inhibited by approximately 13 and 8% respectively when microsomal preparations from TAS and HW animals were incubated with 50 uM vitamin K1 and 10 uM warfarin.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:33:03 GMT 2023
Edited
by admin
on Fri Dec 15 16:33:03 GMT 2023
Record UNII
I47IU4FOCO
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
WARFARIN POTASSIUM
ORANGE BOOK   WHO-DD  
Common Name English
WARFARIN POTASSIUM [ORANGE BOOK]
Common Name English
POTASSIUM WARFARIN
Common Name English
WARFARIN-POTASSIUM
ISO  
Common Name English
WARFARIN POTASSIUM [JAN]
Common Name English
Warfarin potassium [WHO-DD]
Common Name English
ATHROMBIN-K
Brand Name English
WARFARIN-POTASSIUM [ISO]
Common Name English
2H-1-BENZOPYRAN-2-ONE, 4-HYDROXY-3-(3-OXO-1-PHENYLBUTYL)-, POTASSIUM SALT
Common Name English
3-(α-Acetonylbenzyl)-4-hydroxycoumarin potassium salt
Common Name English
Classification Tree Code System Code
EPA PESTICIDE CODE 86005
Created by admin on Fri Dec 15 16:33:03 GMT 2023 , Edited by admin on Fri Dec 15 16:33:03 GMT 2023
NCI_THESAURUS C45597
Created by admin on Fri Dec 15 16:33:03 GMT 2023 , Edited by admin on Fri Dec 15 16:33:03 GMT 2023
Code System Code Type Description
CAS
2610-86-8
Created by admin on Fri Dec 15 16:33:03 GMT 2023 , Edited by admin on Fri Dec 15 16:33:03 GMT 2023
PRIMARY
SMS_ID
100000076722
Created by admin on Fri Dec 15 16:33:03 GMT 2023 , Edited by admin on Fri Dec 15 16:33:03 GMT 2023
PRIMARY
ALANWOOD
warfarin-potassium
Created by admin on Fri Dec 15 16:33:03 GMT 2023 , Edited by admin on Fri Dec 15 16:33:03 GMT 2023
PRIMARY
NCI_THESAURUS
C66658
Created by admin on Fri Dec 15 16:33:03 GMT 2023 , Edited by admin on Fri Dec 15 16:33:03 GMT 2023
PRIMARY
EPA CompTox
DTXSID5042324
Created by admin on Fri Dec 15 16:33:03 GMT 2023 , Edited by admin on Fri Dec 15 16:33:03 GMT 2023
PRIMARY
CHEBI
32301
Created by admin on Fri Dec 15 16:33:03 GMT 2023 , Edited by admin on Fri Dec 15 16:33:03 GMT 2023
PRIMARY
FDA UNII
I47IU4FOCO
Created by admin on Fri Dec 15 16:33:03 GMT 2023 , Edited by admin on Fri Dec 15 16:33:03 GMT 2023
PRIMARY
EVMPD
SUB15716MIG
Created by admin on Fri Dec 15 16:33:03 GMT 2023 , Edited by admin on Fri Dec 15 16:33:03 GMT 2023
PRIMARY
PUBCHEM
23706212
Created by admin on Fri Dec 15 16:33:03 GMT 2023 , Edited by admin on Fri Dec 15 16:33:03 GMT 2023
PRIMARY
RXCUI
82118
Created by admin on Fri Dec 15 16:33:03 GMT 2023 , Edited by admin on Fri Dec 15 16:33:03 GMT 2023
PRIMARY RxNorm
DRUG BANK
DBSALT001410
Created by admin on Fri Dec 15 16:33:03 GMT 2023 , Edited by admin on Fri Dec 15 16:33:03 GMT 2023
PRIMARY
ChEMBL
CHEMBL1464
Created by admin on Fri Dec 15 16:33:03 GMT 2023 , Edited by admin on Fri Dec 15 16:33:03 GMT 2023
PRIMARY
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