PHENPROCOUMON

US Previously Marketed

Details

Stereochemistry	RACEMIC
Molecular Formula	C18H16O3
Molecular Weight	280.3178
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC(C1=CC=CC=C1)C2=C(O)C3=C(OC2=O)C=CC=C3

InChI

InChIKey=DQDAYGNAKTZFIW-UHFFFAOYSA-N

InChI=1S/C18H16O3/c1-2-13(12-8-4-3-5-9-12)16-17(19)14-10-6-7-11-15(14)21-18(16)20/h3-11,13,19H,2H2,1H3

HIDE SMILES / InChI

Description
Sources: https://www.medikamente-per-klick.de/images/ecommerce/04/42/04421738_2010-05_de_o.pdf
Curator's Comment: description was created based on several sources, including: http://www.wikidoc.org/index.php/Phenprocoumon | http://vardgivarwebb.regionostergotland.se/pages/233476/Marcoumar%202000.pdf | https://www.ncbi.nlm.nih.gov/pubmed/18464049 | https://www.ncbi.nlm.nih.gov/pubmed/?term=16372822 | http://www.infomed.ch/100drugs/phenadre.html

Phenprocoumon is the dominant anticoagulant in clinical use in several continental European countries. It used for the prevention and treatment of thromboembolic disease including venous thrombosis, thromboembolism, and pulmonary embolism as well as for the prevention of ischemic stroke in patients with atrial fibrillation. Phenprocoumon inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). Bleedings are the most important side -effects of oral anticoagulants. The gastrointestinal and the urinary tract are often affected; the most dangerous are intracerebral hemorrhages. A great number of drugs increase the risk of bleeding of oral anticoagulants. Enzyme inhibitors (e.g. allopurinol, androgens, cimetidine, ciprofloxacin, co-trimoxazole, certain anti-inflammatory agents, fibrates, imidazoles, macrolide antibiotics, etc.) reinforce, and enzyme inducers (e.g. barbiturates, rifampicin) and oral contraceptives reduce, the anticoagulant action.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Vitamin k epoxide reductase complex subunit 1 isoform 1 22 Target ID: CHEMBL1930 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3490277 \| https://www.ncbi.nlm.nih.gov/pubmed/18464049	Inhibitor 8504	1.8 µM [IC50]
Cytochrome P450 2C9 50 Target ID: CHEMBL3397 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=16372822 \| https://www.ncbi.nlm.nih.gov/pubmed/15054565 \| https://www.ncbi.nlm.nih.gov/pubmed/15054565	Substrate 661
Cytochrome P450 3A4 127 Target ID: CHEMBL340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=16372822	Substrate 661

Conditions

Condition	Modality	Highest Phase	Product
Venous thrombosis 9 Sources: http://www.medicatione.com/?c=drug&s=liquamar&ingredient=phenprocoumon http://vardgivarwebb.regionostergotland.se/pages/233476/Marcoumar%202000.pdf	Preventing	Approved 8583	LIQUAMAR Approved Use Used for the prevention and treatment of thromboembolic disease including venous thrombosis, thromboembolism, and pulmonary embolism as well as for the prevention of ischemic stroke in patients with atrial fibrillation (AF). Launch Date 1957
Thromboembolism 8 Sources: http://www.medicatione.com/?c=drug&s=liquamar&ingredient=phenprocoumon http://vardgivarwebb.regionostergotland.se/pages/233476/Marcoumar%202000.pdf	Preventing	Approved 8583	LIQUAMAR Approved Use Used for the prevention and treatment of thromboembolic disease including venous thrombosis, thromboembolism, and pulmonary embolism as well as for the prevention of ischemic stroke in patients with atrial fibrillation (AF). Launch Date 1957
Pulmonary embolism 19 Sources: http://www.medicatione.com/?c=drug&s=liquamar&ingredient=phenprocoumon http://vardgivarwebb.regionostergotland.se/pages/233476/Marcoumar%202000.pdf	Preventing	Approved 8583	LIQUAMAR Approved Use Used for the prevention and treatment of thromboembolic disease including venous thrombosis, thromboembolism, and pulmonary embolism as well as for the prevention of ischemic stroke in patients with atrial fibrillation (AF). Launch Date 1957
Ischemic stroke 35 Sources: http://www.medicatione.com/?c=drug&s=liquamar&ingredient=phenprocoumon	Preventing	Approved 8583	LIQUAMAR Approved Use Used for the prevention and treatment of thromboembolic disease including venous thrombosis, thromboembolism, and pulmonary embolism as well as for the prevention of ischemic stroke in patients with atrial fibrillation (AF). Launch Date 1957

C_max

Value	Dose	Co-administered	Analyte	Population
2 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15128047/	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENPROCOUMON, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.1 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15128047/	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENPROCOUMON, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
89.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15128047/	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENPROCOUMON, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
105.1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15128047/	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENPROCOUMON, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
123 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15128047/	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENPROCOUMON, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
149 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15128047/	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENPROCOUMON, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 2052 CYP2C8 810

Drug as victim

Target	Modality	Activity
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15054565/	major
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15054565/	major
CYP2C8 810	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15054565/	minor
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23663291/	minor

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:50438	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:50438
ChemicalBook	CB1295890	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1295890
MolPort	MolPort-005-935-554	https://www.molport.com/shop/molecule-link/MolPort-005-935-554

PubMed

Title	Date	PubMed
[Acute paraplegia].	2004-04	15004681
Safety and efficacy of enoxaparin compared with unfractionated heparin and oral anticoagulants for prevention of thromboembolic complications in cardioversion of nonvalvular atrial fibrillation: the Anticoagulation in Cardioversion using Enoxaparin (ACE) trial.	2004-03-02	14967716
[Prevention of deep vein thrombosis in surgical departments].	2004-03	14999395
Clinical significance of PlA polymorphism of platelet GP IIb/IIIa receptors during long-term VAD support.	2004-03	14992889
Ginger-associated overanticoagulation by phenprocoumon.	2004-02	14742762
[Thrombus attached to a Sideris septal occluder system 6 years later].	2004-01-16	14724782
The use of vitamin K in patients on anticoagulant therapy: a practical guide.	2004	14967065
Determination of (R)- and (S)-phenprocoumon in human plasma by enantioselective liquid chromatography/electrospray ionisation tandem mass spectrometry.	2004	14966853
[Surgical treatment of aortic valve disease in old age].	2003-12-18	14974324
[Therapy and secondary prevention of venous thromboembolism with vitamin K antagonists].	2003-12	14689191
Phenprocoumon-induced hepatitis as an immunologically mediated drug allergic complication of antithrombotic therapy.	2003-12	14652659
Comparison of the quality of oral anticoagulant therapy through patient self-management and management by specialized anticoagulation clinics in the Netherlands: a randomized clinical trial.	2003-11-24	14638565
[Are there guidelines for performance of coloscopy during drug anticoagulation?].	2003-10-31	14593580
[How should anticoagulants be used in recurrent, ischemic and hemorrhagic brain infarctions?].	2003-10-17	14562222
Oral anticoagulation for ECG tremor artefact simulating atrial fibrillation.	2003-10	14609309
[Phenprocoumon-induced liver failure].	2003-09-12	12970822
[When should vaccination of phenprocoumon patients take place?].	2003-09-05	14518438
Recurrent thrombosis despite anticoagulation in a man with monocytosis. Case 8.	2003-08	12923583
Life threatening bleeding under adequate oral anticoagulation. Cases 4a, b.	2003-08	12923579
A prospective and randomized comparison of the safety and effects of therapeutic levels of enoxaparin versus unfractionated heparin in chronically anticoagulated patients undergoing elective cardiac catheterization.	2003-08	12888874
Comparison of control and stability of oral anticoagulant therapy using acenocoumarol versus phenprocoumon.	2003-08	12888873
Recurrent deep-vein thrombosis based on homozygous factor V Leiden mutation acquired after liver transplantation.	2003-08	12884202
Anticoagulation with the low-molecular-weight heparin dalteparin (Fragmin) in atrial fibrillation and TEE-guided cardioversion.	2003-07	12883837
Determination of bleeding risk using genetic markers in patients taking phenprocoumon.	2003-07	12728288
[Secondary prevention after stroke: healthy life style, oral anticoagulation].	2003-05-26	14579487
[Clinical and hemodynamic results of the mosaic bioprosthesis in aortic position].	2003-05	12966833
[Congenital heart disease and acquired valvular lesions in pregnancy].	2003-05	12756480
Pharmacogenetics of oral anticoagulants.	2003-05	12724615
Sustained intake of paracetamol (acetaminophen) during oral anticoagulant therapy with coumarins does not cause clinically important INR changes: a randomized double-blind clinical trial.	2003-04	12871405
Isolated coronary artery rupture after blunt chest trauma.	2003-04	12730819
[Septic thrombosis of the cavernous sinus due to folliculitis].	2003-04	12669208
Spontaneous, self-limited, non-atherosclerotic dissection of the superior mesenteric artery.	2003-04	12655268
[The first oral thrombin inhibitor. Competition to heparins and marcumar?].	2003-03-06	12688030
Coagulopathy and outcome in patients with chronic subdural haematoma.	2003-02	12580860
Clopidogrel and aspirin in the prevention of thromboembolic complications after mechanical aortic valve replacement (CAPTA).	2003-01-25	12706642
Outpatient treatment of pulmonary embolism is feasible and safe in a substantial proportion of patients.	2003-01	12871557
[Clinical problems with oral anticoagulation -- 3 case reports].	2003-01	12638482
[Oral anticoagulation with vitamin K antagonists].	2003-01	12638470
[Case report. Phenprocoumon (Marcumar, Falithrom) as an unusual reason for coumarin poisoning in a dog].	2003-01	12596669
Effects of lepirudin, argatroban and melagatran and additional influence of phenprocoumon on ecarin clotting time.	2003	14644085
Acenocoumarol is not a safe alternative for anticoagulation in phenprocoumon-induced hepatic failure. Report of two cases.	2003	12743448
Treatment of subclavian-axillary vein thrombosis: long-term outcome of anticoagulation versus systemic thrombolysis.	2002-12-15	12676186
[Malpractice in determination of INR value in ambulatory care].	2002-12	12607400
Exacerbation of antiphospholipid antibody syndrome after treatment of localized cancer: a report of two cases.	2002-12	12483370
Anticoagulant-related iliopsoas muscle bleeding leading to fatal exsanguination: report of two autopsy cases.	2002-12	12464809
Overanticoagulation associated with combined use of antibacterial drugs and acenocoumarol or phenprocoumon anticoagulants.	2002-11	12428081
Effect of phenprocoumon on monitoring of lepirudin, argatroban, melagatran and unfractionated heparin with the PiCT method.	2002-05-03	12759518
[Livedo racemosa, skin necrosis at the basal toe joint].	1992-08-25	1410981
A spinal haematoma occurring in the subarachnoid as well as in the subdural space in a patient treated with anticoagulants.	1992	1321696
Effect in man of a new indandione anticoagulant.	1952-12	13037763

Patents

Sample Use Guides

In Vivo Use Guide

1st day single dose - 12-15 mg, 2nd day single dose - 6-9 mg. Treatment continues with lower doses - 1.5 - 6 mg daily as a maintenance dose.

Route of Administration: Oral

In Vitro Use Guide

At a given cholestyramine concentration (0.1 gm/100 rnI) the percentage phenprocoumon bound remained nearly constant in the 1 to 75 fLg/ml concentration range of phenprocoumon.

Name

Type

Language

LIQUAMAR

Preferred Name

English

PHENPROCOUMON

Official Name

English

PHENPROCOUMON [ORANGE BOOK]

Common Name

English

PHENPROCOUMON [USAN]

Common Name

English

2H-1-BENZOPYRAN-2-ONE, 4-HYDROXY-3-(1-PHENYLPROPYL)-

Systematic Name

English

MARCOUMAR

Common Name

English

DL-3-(.ALPHA.-ETHYLBENZYL)-4-HYDROXYCOUMARIN

Common Name

English

PHENPROCOUMAROL

Common Name

English

FALITHROM

Systematic Name

English

PHENPROCOUMON [MI]

Common Name

English

(±)-PHENPROCOUMON

Common Name

English

phenprocoumon [INN]

Common Name

English

FENCUMAR

Common Name

English

PHENPROCOUMON [VANDF]

Common Name

English

3-(?-Ethylbenzyl)-4-hydroxycoumarin

Systematic Name

English

MARCUMAR

Common Name

English

PHENPROCOUMAROLE

Common Name

English

Phenprocoumon [WHO-DD]

Common Name

English

PHENPROCOUMON [HSDB]

Common Name

English

COUMARIN, 3-(.ALPHA.-ETHYLBENZYL)-4-HYDROXY-

Systematic Name

English

RO-1-4849

Code

English

3-(1-PHENYLPROPYL)-4-HYDROXYCOUMARIN

Systematic Name

English

4-HYDROXY-3-(1-PHENYLPROPYL)-2H-1-BENZOPYRAN-2-ONE

Systematic Name

English

PHENPROCOUMON [MART.]

Common Name

English

3-(.ALPHA.-PHENYLPROPYL)-4-HYDROXYCOUMARIN

Systematic Name

English

BS-7565

Code

English

4-HYDROXY-2-OXO-3-(1-PHENYLPROPYL)-2H-CHROMENE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C263