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Details

Stereochemistry RACEMIC
Molecular Formula C19H16O4
Molecular Weight 308.3287
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of WARFARIN

SMILES

CC(=O)CC(c1ccccc1)c2c(c3ccccc3oc2=O)O

InChI

InChIKey=PJVWKTKQMONHTI-UHFFFAOYSA-N
InChI=1S/C19H16O4/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

HIDE SMILES / InChI
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

-4.91270406E11
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

-4.91270406E11
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

-4.91270406E11
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
Chondrodysplasia punctata and maternal warfarin use during pregnancy.
1975 Mar
Central retinal vein occlusion associated with primary pulmonary hypertension.
2001
Abdominal wall hematoma as a complication of warfarinization.
2001 Apr
Spontaneous subcapsular renal hematoma secondary to anticoagulant therapy.
2001 Apr
Behçet's disease with a large intracardiac thrombus: a case report.
2001 Apr
Perioperative management and reversal of antithrombotic therapy.
2001 Feb
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
Anticoagulation and cataract surgery: a review of the current literature.
2001 Feb
[Incidence of tumors after treatment with oral anticoagulants].
2001 Feb
Risks and benefits of adding anti-platelet therapy to warfarin among patients with prosthetic heart valves: a meta-analysis.
2001 Feb
Subtherapeutic INR values associated with a switch to generic warfarin.
2001 Feb
Current trends in the management of deep venous thrombosis and postthrombotic syndrome.
2001 Feb
Anticoagulant pharmacodynamics of tinzaparin following 175 iu/kg subcutaneous administration to healthy volunteers.
2001 Feb 15
Central venous device-related infection and thrombosis in patients treated with moderate dose continuous-infusion interleukin-2.
2001 Feb 15
What is the best emergency treatment for children who ingest warfarin rodenticide?
2001 Feb 5
[Old adrenal hematoma: a case report].
2001 Jan
Regarding postoperative stroke after warfarin for cutaneous surgery.
2001 Jan
Catastrophic antiphospholipid antibody syndrome.
2001 Jan
Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors.
2001 Jan
Need for increased dose of warfarin in HIV patients taking nevirapine.
2001 Jan 26
Acute spontaneous haematoma of the rectum.
2001 Jan-Feb
Sneddon's syndrome: a case report.
2001 Mar
Perception of teratogenic risk of common medicines.
2001 Mar
Long-term results of venous revascularization for Paget-Schroetter syndrome in athletes.
2001 Mar
Prevention, diagnosis, and treatment of venous thromboembolic complications of gynecologic surgery.
2001 Mar
Increase in international normalized ratio associated with smoking cessation.
2001 Mar
The association of vitamin K status with warfarin sensitivity at the onset of treatment.
2001 Mar
A case report of warfarin resistance due to azathioprine and review of the literature.
2001 Mar
Evaluation of very low-dose subcutaneous vitamin K during postoperative warfarin therapy.
2001 Mar
Palliative care for the elderly.
2001 Mar
Treatment of the patient with deep vein thrombosis.
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
Improving medication safety across a multihospital system.
2001 Mar
Potential clinical efficacy and cost benefit of a transesophageal echocardiography-guided low-molecular-weight heparin (enoxaparin) approach to antithrombotic therapy in patients undergoing immediate cardioversion from atrial fibrillation.
2001 Mar
Atrial fibrillation and stroke : concepts and controversies.
2001 Mar
Low-dose warfarin fails to prolong survival of dual lumen venous dialysis catheters.
2001 Mar
Mutations of the CYP2C9 gene and the response to warfarin.
2001 Mar
Antiphospholipid antibody syndrome and renal disease.
2001 Mar
When should an effective treatment be used? Derivation of the threshold number needed to treat and the minimum event rate for treatment.
2001 Mar
Management of thrombosis in women with antiphospholipid syndrome.
2001 Mar
Mild head injury, anticoagulants, and risk of intracranial injury.
2001 Mar 10
Dalteparin vs warfarin in hip arthroplasty patients.
2001 Mar 12
Profile of moxifloxacin drug interactions.
2001 Mar 15
Subarachnoid haemorrhage.
2001 Mar 17
Warfarin therapy for an octogenarian who has atrial fibrillation.
2001 Mar 20
Vitamin K for warfarin-associated coagulopathy.
2001 Mar 3
Clinical trials that have influenced the treatment of venous thromboembolism: a historical perspective.
2001 Mar 6
What is the optimal medical management of ischemic heart failure?
2001 Mar-Apr
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.
Name Type Language
WARFARIN
HSDB   INN   ISO   MI   USP-RS   VANDF   WHO-DD  
INN  
Official Name English
NSC-59813
Code English
(+/-)-4-HYDROXY-3-(3-OXO-1-PHENYLBUTYL)-2H-1-BENZOPYRAN-2-ONE
Systematic Name English
WARFARIN [INN]
Common Name English
WARFARIN [MI]
Common Name English
WARFARIN [WHO-DD]
Common Name English
WARFARIN [USP-RS]
Common Name English
WARFARIN [VANDF]
Common Name English
WARFARIN [ISO]
Common Name English
WARFARIN [HSDB]
Common Name English
CHOICE
Brand Name English
4-HYDROXY-3-(3-OXO-1-PHENYLBUTYL)-2H-1-BENZOPYRAN-2-ONE
Systematic Name English
4-HYDROXY-3-((1RS)-3-OXO-1-PHENYLBUTYL)COUMARIN
Systematic Name English
Classification Tree Code System Code
NDF-RT N0000175964
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
WHO-ATC B01AA03
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
WHO-VATC QB01AA03
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
NCI_THESAURUS C263
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
LIVERTOX 1041
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
NCI_THESAURUS C45597
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 10.2
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
NDF-RT N0000175476
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
EPA PESTICIDE CODE 86002
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C945
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY
IUPHAR
6853
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY
INN
341
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY
RXCUI
11289
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY RxNorm
WIKIPEDIA
WARFARIN
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY
CAS
81-81-2
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY
LACTMED
Warfarin
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY
EPA CompTox
81-81-2
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY
EVMPD
SUB00090MIG
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY
PUBCHEM
54678486
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY
FDA UNII
5Q7ZVV76EI
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY
ECHA (EC/EINECS)
201-377-6
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY
ChEMBL
CHEMBL1464
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY
DRUG BANK
DB00682
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY
HSDB
1786
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY
MERCK INDEX
M11506
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY Merck Index
USP_CATALOG
1719000
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY USP-RS
DRUG CENTRAL
2847
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY
MESH
D014859
Created by admin on Sat Jun 26 05:48:35 UTC 2021 , Edited by admin on Sat Jun 26 05:48:35 UTC 2021
PRIMARY