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Identification
NameAcenocoumarol
Accession NumberDB01418
Typesmall molecule
Groupsapproved
Description

Acenocoumarol is a coumarin derivative used as an anticoagulant. Coumarin derivatives inhibit the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of vitamin K-dependent clotting factors, II, VII, XI and X, and interferes with coagulation. Hematocrit, hemoglobin, international normalized ratio and liver panel should be monitored. Patients on acenocoumarol are prohibited from giving blood.

Structure
Thumb
Synonyms
SynonymLanguageCode
3-(alpha-(4'-Nitrophenyl)-beta-acetylethyl)-4-hydroxycoumarinNot AvailableNot Available
3-(alpha-(P-Nitrophenol)-beta-acetylethyl)-4-hydroxycoumarinNot AvailableNot Available
3-(alpha-Acetonyl-4-nitrobenzyl)-4-hydroxycoumarinNot AvailableNot Available
3-(alpha-Acetonyl-P-nitrobenzyl)-4-hydroxycoumarinNot AvailableNot Available
3-(alpha-P-Nitrophenyl-beta-acetylethyl)-4-hydroxycoumarinNot AvailableNot Available
4-Hydroxy-3-(1-(4-nitrophenyl)-3-oxobutyl)-2H-1-benzopyran-2-oneNot AvailableNot Available
4-Hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-oneNot AvailableNot Available
AcenocoumarinNot AvailableNot Available
AcenocoumarolumLatinINN
AcenocumarolNot AvailableNot Available
AcenocumaroloNot AvailableNot Available
AcenokumarinNot AvailableNot Available
NicoumaloneNot AvailableNot Available
NicumalonNot AvailableNot Available
Nitrophenylacetylethyl-4-hydroxycoumarineNot AvailableNot Available
NitrovarfarianNot AvailableNot Available
NitrowarfarinNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AscumarStar
Mini-sintromNot Available
SinkumarNot Available
SintromPaladin
Brand mixturesNot Available
Categories
CAS number152-72-7
WeightAverage: 353.3255
Monoisotopic: 353.089937217
Chemical FormulaC19H15NO6
InChI KeyVABCILAOYCMVPS-UHFFFAOYSA-N
InChI
InChI=1S/C19H15NO6/c1-11(21)10-15(12-6-8-13(9-7-12)20(24)25)17-18(22)14-4-2-3-5-16(14)26-19(17)23/h2-9,15,22H,10H2,1H3
IUPAC Name
4-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-one
SMILES
CC(=O)CC(C1=CC=C(C=C1)[N+]([O-])=O)C1=C(O)C2=CC=CC=C2OC1=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassPhenylpropanoids and Polyketides
ClassCoumarins and Derivatives
SubclassNot Available
Direct parentCoumarins and Derivatives
Alternative parentsBenzopyrans; Nitrobenzenes; Pyranones and Derivatives; Nitro Compounds; Ketones; Nitronic Acids; Polyamines; Enolates; Organic Oxoazanium Compounds
Substituentsnitrobenzene; pyranone; pyran; benzene; nitronic acid; nitro compound; ketone; polyamine; enolate; organic oxoazanium; organonitrogen compound; amine; carbonyl group
Classification descriptionThis compound belongs to the coumarins and derivatives. These are polycyclic aromatic compounds containing a 1-benzopyran moiety with a ketone group at the C2 carbon atom (1-benzopyran-2-one).
Pharmacology
IndicationFor the treatment and prevention of thromboembolic diseases. More specifically, it is indicated for the for the prevention of cerebral embolism, deep vein thrombosis, pulmonary embolism, thromboembolism in infarction and transient ischemic attacks. It is used for the treatment of deep vein thrombosis and myocardial infarction.
PharmacodynamicsAcenocoumarol inhibits the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of certain glutamic acid residues near the N-terminals of clotting factors II, VII, IX and X, the vitamin K-dependent clotting factors. Glutamic acid carboxylation is important for the interaction between these clotting factors and calcium. Without this interaction, clotting cannot occur. Both the extrinsic (via factors VII, X and II) and intrinsic (via factors IX, X and II) are affected by acenocoumarol.
Mechanism of actionAcenocoumarol inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent clotting factors, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited resulting in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.
AbsorptionRapidly absorbed orally with greater than 60% bioavailability. Peak plasma levels are attained 1 to 3 hours following oral administration.
Volume of distribution

The volume of distribution at steady-state appeared to be significantly dose dependent: 78 ml/kg for doses < or = 20 microg/kg and 88 ml/kg for doses > 20 microg/kg respectively

Protein binding98.7% protein bound, mainly to albumin
Metabolism

Extensively metabolized in the liver via oxidation forming two hydroxy metabolites and keto reduction producing two alcohol metabolites. Reduction of the nitro group produces an amino metabolite which is further transformed to an acetoamido metabolite. Metabolites do not appear to be pharmacologically active.

SubstrateEnzymesProduct
Acenocoumarol
6-Hydroxy-R-acenocoumarolDetails
Acenocoumarol
7-Hydroxy-R-acenocoumarolDetails
Acenocoumarol
8-Hydroxy-R-acenocoumarolDetails
Route of eliminationMostly via the kidney as metabolites
Half life8 to 11 hours.
ClearanceNot Available
ToxicityThe onset and severity of the symptoms are dependent on the individual's sensitivity to oral anticoagulants, the severity of the overdosage, and the duration of treatment. Bleeding is the major sign of toxicity with oral anticoagulant drugs. The most frequent symptoms observed are: cutaneous bleeding (80%), haematuria (with renal colic) (52%), haematomas, gastrointestinal bleeding, haematemesis, uterine bleeding, epistaxis, gingival bleeding and bleeding into the joints. Further symptoms include tachycardia, hypotension, peripheral circulatory disorders due to loss of blood, nausea, vomiting, diarrhoea and abdominal pains.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Acenocoumarol Action PathwayDrug actionSMP00269
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.7518
Blood Brain Barrier + 0.5765
Caco-2 permeable + 0.5
P-glycoprotein substrate Non-substrate 0.6031
P-glycoprotein inhibitor I Non-inhibitor 0.7078
P-glycoprotein inhibitor II Non-inhibitor 0.843
Renal organic cation transporter Non-inhibitor 0.8944
CYP450 2C9 substrate Non-substrate 0.6256
CYP450 2D6 substrate Non-substrate 0.8936
CYP450 3A4 substrate Substrate 0.6267
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Inhibitor 0.8949
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.831
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7492
Ames test AMES toxic 0.6954
Carcinogenicity Non-carcinogens 0.7015
Biodegradation Not ready biodegradable 0.9403
Rat acute toxicity 2.7869 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.6326
hERG inhibition (predictor II) Non-inhibitor 0.9347
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral1 mg
TabletOral4 mg
Prices
Unit descriptionCostUnit
Sintrom 4 mg Tablet1.6USDtablet
Sintrom 1 mg Tablet0.51USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point196-199Merck Index 23
water solubilitypractically insolubleMSDS
logP1.98SANGSTER (1994)
Predicted Properties
PropertyValueSource
water solubility1.06e-02 g/lALOGPS
logP2.53ALOGPS
logP2.68ChemAxon
logS-4.5ALOGPS
pKa (strongest acidic)5.79ChemAxon
pKa (strongest basic)-6.8ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count1ChemAxon
polar surface area109.42ChemAxon
rotatable bond count5ChemAxon
refractivity94.18ChemAxon
polarizability34.35ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Stoll, W. and Litvan, F.; U.S. Patent 2,648,682; August 11,1953; assigned to J.R. Geigy A.G.,
Switzerland.

General Reference
  1. Cesar JM, Garcia-Avello A, Navarro JL, Herraez MV: Aging and oral anticoagulant therapy using acenocoumarol. Blood Coagul Fibrinolysis. 2004 Oct;15(8):673-6. Pubmed
  2. Lengyel M: [Warfarin or acenocoumarol is better in the anticoagulant treatment of chronic atrial fibrillation?] Orv Hetil. 2004 Dec 26;145(52):2619-21. Pubmed
  3. Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. Pubmed
  4. Montes R, Ruiz de Gaona E, Martinez-Gonzalez MA, Alberca I, Hermida J: The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients. Br J Haematol. 2006 Apr;133(2):183-7. Pubmed
  5. Girard P, Nony P, Erhardtsen E, Delair S, Ffrench P, Dechavanne M, Boissel JP: Population pharmacokinetics of recombinant factor VIIa in volunteers anticoagulated with acenocoumarol. Thromb Haemost. 1998 Jul;80(1):109-13. Pubmed
External Links
ResourceLink
KEGG DrugD07064
ChEBI53766
ChEMBLCHEMBL397420
Therapeutic Targets DatabaseDAP000772
PharmGKBPA452632
Drug Product Database10383
WikipediaAcenocoumarol
ATC CodesB01AA07
AHFS Codes
  • 20:12.04.08
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(126 KB)
Interactions
Drug Interactions
Drug
AcetaminophenAcetaminophen may increase the anticoagulant effect of acenocoumarol. Monitor for changes in the therapeutic and adverse effects of acenocoumarol if acetaminophen is initiated, discontinued or dose changed.
Acetylsalicylic acidAcetylsalicylic acid increases the effect of the anticoagulant, acenocoumarol.
AllopurinolAllopurinol may increase the anticoagulant effect of acenocoumarol.
AminoglutethimideAminoglutethimide may decrease the anticoagulant effect of acenocoumarol.
AmiodaroneAmiodarone may increase the anticoagulant effect of acenocoumarol.
AmprenavirAmprenavir may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration.
AprepitantAprepitant may decrease the anticoagulant effect of acenocoumarol by decreasing its serum concentration.
AtazanavirThe protease inhibitor, atazanavir, may increase the anticoagulant effect of acenocoumarol.
AzathioprineAzathioprine may decrease the anticoagulant effect of acenocoumarol.
AzithromycinAzithromycin may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration.
BetamethasoneThe corticosteroid, betamethasone, alters the anticoagulant effect, acenocoumarol.
BosentanBosentan may decrease the anticoagulant effect of acenocoumarol by increasing its metabolism.
ButabarbitalBarbiturates like butabarbital may increase the metabolism of Vitamin K Antagonists like acenocoumarol. onitor for decreased therapeutic effects of oral anticoagulants if a barbiturate is initiated/dose increased (anticoagulant dosage increases of 30% to 60% may be needed based on monitored PT), or increased effects if a barbiturate is discontinued/dose decreased. An increased frequency of PT monitoring should be considered for the period immediately following barbiturate initiation/dosage changes.
ButalbitalBarbiturates such as butalbital may increase the metabolism of Vitamin K Antagonists such as acenocoumarol. Monitor for decreased therapeutic effects of oral anticoagulants if a barbiturate is initiated/dose increased (anticoagulant dosage increases of 30% to 60% may be needed based on monitored PT), or increased effects if a barbiturate is discontinued/dose decreased. An increased frequency of PT monitoring should be considered for the period immediately following barbiturate initiation/dosage changes.
CapecitabineCapecitabine may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration.
CarbamazepineCarbamazepine may decrease the anticoagulant effect of acenocoumarol by decreasing its serum concentration.
CefotetanThe cephalosporin, cefotetan, may increase the anticoagulant effect of acenocoumarol.
CefoxitinThe cephalosporin, cefoxitin, may increase the anticoagulant effect of acenocoumarol.
CeftriaxoneThe cephalosporin, ceftriaxone, may increase the anticoagulant effect of acenocoumarol.
CelecoxibCelecoxib may increase the anticoagulant effect of acenocoumarol.
CholestyramineThe bile acid sequestrant, cholestyramine, may decrease the anticoagulant effect of acenocoumarol by decreasing its absorption.
CimetidineCimetidine may increase the anticoagulant effect of acenocoumarol.
CiprofloxacinThe quinolone antibiotic, ciprofloxacin, may increase the anticoagulant effect of acenocoumarol.
CisaprideCisapride may increase the anticoagulant effect of acenocoumarol.
CitalopramThe SSRI, citalopram, increases the effect of anticoagulant, acenocoumarol.
ClarithromycinThe macrolide, clarithromycin, may increase the anticoagulant effect of acenocoumarol.
ClofibrateThe fibrate increases the anticoagulant effect
ColestipolThe bile acid sequestrant, colestipol, may decrease the anticoagulant effect of acenocoumarol by decreasing its absorption.
CyclophosphamideThe antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of acenocoumarol.
DanazolThe androgen, danazol, may increase the anticoagulant effect of acenocoumarol.
DemeclocyclineThe tetracycline, demeclocycline, may increase the anticoagulant effect of acenocoumarol.
DexamethasoneThe corticosteroid, dexamethasone, alters the anticoagulant effect, acenocoumarol.
DextropropoxyphenePropoxyphene may increase the anticoagulant effect of acenocoumarol.
DextrothyroxineThe thyroid hormone, dextrothyroxine, increase the anticoagulant effect of acenocoumarol.
DicloxacillinDicloxacillin may decrease the anticoagulant effect of acenocoumarol.
DiflunisalThe NSAID, diflunisal, may increase the anticoagulant effect of acenocoumarol.
DisulfiramDisulfiram may increase the anticoagulant effect of acenocoumarol.
DoxycyclineThe tetracycline, doxycycline, may increase the anticoagulant effect of acenocoumarol.
ErythromycinThe macrolide, erythromycin, may increase the anticoagulant effect of acenocoumarol.
EthchlorvynolEthchlorvynol may decrease the anticoagulant effect of acenocoumarol.
Ethinyl EstradiolIncreased thrombotic risk due to estrogen
EtodolacThe NSAID, etodolac, may increase the anticoagulant effect or acenocoumarol.
EtoricoxibEtoricoxib may increase the anticoagulant effect of acenocoumarol.
FenofibrateFenofibrate may increase the anticoagulant effect of acenocoumarol.
FenoprofenThe NSAID, fenoprofen, may increase the anticoagulant effect of acenocoumarol.
FluconazoleFluconazole may increase the serum concentration of acenocoumarol by decreasing its metabolism.
FludrocortisoneThe corticosteroid, fludrocortisone, alters the anticoagulant effect, acenocoumarol.
FluorouracilThe antineoplasic agent, fluorouracil, may increase the anticoagulant effect of acenocoumarol.
FluoxetineThe SSRI, fluoxetine, increases the effect of anticoagulant, acenocoumarol.
FluoxymesteroneThe androgen, fluoxymesterone, may increase the anticoagulant effect of acenocoumarol.
FlurbiprofenThe NSAID, flurbiprofen, may increase the anticoagulant effect of acenocoumarol.
FluvastatinFluvastatin may increase the anticoagulant effect of acenocoumarol. Monitor for changes in the therapeutic and adverse effects of acenocoumarol if fluvastatin is initiated, discontinued or dose changed.
FluvoxamineFluvoxamine may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration.
FosamprenavirThe protease inhibitor, fosamprenavir, may increase the anticoagulant effect of acenocoumarol.
FosphenytoinIncreased hydantoin levels and risk of bleeding
GefitinibGefitinib may increase the anticoagulant effect of acenocoumarol.
GemcitabineGemcitabine may increase the anticoagulant effect of acenocoumarol.
GemfibrozilGemfibrozil may increase the anticoagulant effect of acenocoumarol.
Ginkgo bilobaAdditive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
GlutethimideGlutethimide may decrease the anticoagulant effect of acenocoumarol.
GriseofulvinGriseofulvin may decrease the anticoagulant effect of acenocoumarol.
HydrocortisoneThe corticosteroid, hydrocortisone, alters the anticoagulant effect, acenocoumarol.
IbuprofenThe NSAID, ibuprofen, may increase the anticoagulant effect of acenocoumarol.
ImatinibImatinib may increase the anticoagulant effect of acenocoumarol.
IndinavirThe protease inhibitor, indinavir, may increase the anticoagulant effect of acenocoumarol.
IndomethacinThe NSAID, indomethacin, may increase the anticoagulant effect of acenocoumarol.
IsoniazidIsoniazid may increase the anticoagulant effect of acenocoumarol.
ItraconazoleItraconazole may increase the anticoagulant effect of acenocoumarol.
KetoconazoleKetoconazole may increase the anticoagulant effect of acenocoumarol.
KetoprofenThe NSAID, ketoprofen, may increase the anticoagulant effect of acenocoumarol.
KetorolacThe NSAID, ketorolac, may increase the anticoagulant effect of acenocoumarol.
LeflunomideLeflunomide may increase the anticoagulant effect of acenocoumarol.
LevamisoleLevamisole may increase the anticoagulant effect of acenocoumarol.
LevofloxacinThe quinolone antibiotic, levofloxacin, may increase the anticoagulant effect of acenocoumarol.
LevothyroxineThe thyroid hormone, levothyroxine, increase the anticoagulant effect of acenocoumarol.
LovastatinLovastatin may increase the anticoagulant effect of acenocoumarol. Monitor for changes in the therapeutic and adverse effects of acenocoumarol if lovastatin is initiated, discontinued or dose changed.
LumiracoxibLumiracoxib may increase the anticoagulant effect of acenocoumarol.
Medroxyprogesterone AcetateMedroxyprogesterone may increase the anticoagulant effect of acenocoumarol.
Mefenamic acidThe NSAID, mefanamic acid, may increase the anticoagulant effect of acenocoumarol.
MefloquineMefloquine may increase the anticoagulant effect of acenocoumarol.
MeloxicamMeloxicam may increase the anticoagulant effect of acenocoumarol.
MercaptopurineMercaptopurine may decrease the anticoagulant effect of acenocoumarol.
MethimazoleThe antithyroid agent, methimazole, may decrease the anticoagulant effect of acenocoumarol.
MetronidazoleMetronidazole may increase the anticoagulant effect of acenocoumarol.
MiconazoleMiconazole may increase the serum concentration of acenocoumarol by decreasing its metabolism.
MinocyclineThe tetracycline, minocycline, may increase the anticoagulant effect of acenocoumarol.
MitotaneMitotane may decrease the anticoagulant effect of acenocoumarol.
MoxifloxacinThe quinolone antibiotic, moxifloxacin, may increase the anticoagulant effect of acenocoumarol.
NabumetoneThe NSAID, nabumetone, may increase the anticoagulant effect of acenocoumarol.
Nalidixic AcidThe quinolone antibiotic, nalidixic acid, may increase the anticoagulant effect of acenocoumarol.
NaproxenThe NSAID, naproxen, may increase the anticoagulant effect of acenocoumarol.
NelfinavirThe protease inhibitor, nelfinavir, may increase the anticoagulant effect of acenocoumarol.
NevirapineNevirapine may decrease the anticoagulant effect of acenocoumarol.
NorfloxacinThe quinolone antibiotic, norfloxacin, may increase the anticoagulant effect of acenocoumarol.
OfloxacinThe quinolone antibiotic, ofloxacin, may increase the anticoagulant effect of acenocoumarol.
OrlistatOrlistat may increase the anticoagulant effect of acenocoumarol.
OxaprozinThe NSAID, oxaprozin, may increase the anticoagulant effect of acenocoumarol.
OxyphenbutazoneThe NSAID, oxyphenbutazone, may increase the anticoagulant effect of acenocoumarol.
ParoxetineThe SSRI, paroxetine, increases the effect of the anticoagulant, acenocoumarol.
PentoxifyllinePentoxifylline may increase the anticoagulant effect of acenocoumarol.
PhenobarbitalThe barbiturate, phenobarbital, decreases the anticoagulant effect of acenocoumarol.
PhenylbutazoneThe NSAID, phenylbutazone, may increase the anticoagulant effect of acenocoumarol.
PhenytoinIncreased hydantoin levels and risk of bleeding
PiroxicamThe NSAID, piroxicam, may increase the anticoagulant effect of acenocoumarol.
PrednisoloneThe corticosteroid, prednisolone, alters the anticoagulant effect, acenocoumarol.
PrednisoneThe corticosteroid, prednisone, alters the anticoagulant effect, acenocoumarol.
PrimidoneThe barbiturate, primidone, decreases the anticoagulant effect of acenocoumarol.
PropafenonePropafenone may increase the anticoagulant effect of acenocoumarol.
PropylthiouracilThe anti-thyroid agent, propylthiouracil, may decrease the anticoagulant effect of acenocoumarol.
QuinidineQuinidine may increase the anticoagulant effect of acenocoumarol.
QuinineQuinine, a moderate CYP2C9 inhibitor, may increase the serum concentration of acenocoumarol by decreasing its metabolism via CYP2C9.
RanitidineRanitidine may increase the anticoagulant effect of acenocoumarol. (Conflicting evidence)
RifabutinRifabutin may decrease the anticoagulant effect of acenocoumarol by increasing its metabolism.
RifampicinRifampin may decrease the anticoagulant effect of acenocoumarol by increasing its metabolism.
SulindacThe NSAID, sulindac, may increase the anticoagulant effect of acenocoumarol. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.
TamoxifenTamoxifen may increase the serum concentration of Acenocoumarol increasing the risk of bleeding. Concomitant therapy should be avoided.
TelithromycinTelithromycin may increase the anticoagulant effect of acenocoumarol.
TenoxicamThe NSAID, tenoxicam, may increase the anticoagulant effect of acenocoumarol.
TestolactoneThe androgen, Testolactone, may incrase the anticoagulant effect of the Vitamin K antagonist, Acenocoumarol. Monitor for changes in the therapeutic effect of Acenocoumarol if Testolactone is initiated, discontinued or dose changed.
TestosteroneThe androgen, Testosterone, may incrase the anticoagulant effect of the Vitamin K antagonist, Acenocoumarol. Monitor for changes in the therapeutic effect of Acenocoumarol if Testosterone is initiated, discontinued or dose changed.
Testosterone PropionateThe androgen, Testosterone, may incrase the anticoagulant effect of the Vitamin K antagonist, Acenocoumarol. Monitor for changes in the therapeutic effect of Acenocoumarol if Testosterone is initiated, discontinued or dose changed.
TetracyclineTetracycline may increase the anticoagulant effect of acenocoumarol.
ThiabendazoleThe strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Acenocoumarol by decreasing Acenocoumarol metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Acenocoumarol if Thiabendazole is initiated, discontinued or dose changed.
ThiopentalThiopental may increase the metabolism of the Vitamin K antagonist, Acenocoumarol. Acenocoumarol dose adjustment may be required.
Tiaprofenic acidIncreased risk of bleeding.
TigecyclineTigecycline may increase the anticoagulant effect of acenocoumarol.
TolbutamideTolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Acenocoumarol. Consider alternate therapy or monitor for changes in Acenocoumarol therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
TolmetinIncreased risk of bleeding. Monitor for signs and symptoms of bleeding.
transdermal testosterone gelThe androgen, Testosterone, may incrase the anticoagulant effect of the Vitamin K antagonist, Acenocoumarol. Monitor for changes in the therapeutic effect of Acenocoumarol if Testosterone is initiated, discontinued or dose changed.
TreprostinilThe prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the anticoagulant, Acenocoumarol. Monitor for increased bleeding during concomitant thearpy.
TriamcinoloneThe corticosteroid, triamcinolone, alters the anticoagulant effect, acenocoumarol.
TrimetrexateThe anticoagulant effect of Acenocoumarol, a Vitamin K antagonist, may be altered by antineoplastics such as Trimetrexate. Monitor for changes in the anticoagulant effects of warfarin and other coumarin derivatives during concomitant use.
ZafirlukastZafirlukast may inhibit the metabolism of the vitamin K antagonist Acenocoumarol and increase INR and risk of bleeding.
Food Interactions
  • High doses of vitamin A, C, E and K (e.g. avocado, green vegetables)

Targets

1. Vitamin K epoxide reductase complex subunit 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Vitamin K epoxide reductase complex subunit 1 Q9BQB6 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Bodin L, Verstuyft C, Tregouet DA, Robert A, Dubert L, Funck-Brentano C, Jaillon P, Beaune P, Laurent-Puig P, Becquemont L, Loriot MA: Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity. Blood. 2005 Jul 1;106(1):135-40. Epub 2005 Mar 24. Pubmed
  3. Gonzalez-Conejero R, Corral J, Roldan V, Ferrer F, Sanchez-Serrano I, Sanchez-Blanco JJ, Marin F, Vicente V: The genetic interaction between VKORC1 c1173t and calumenin a29809g modulates the anticoagulant response of acenocoumarol. J Thromb Haemost. 2007 Aug;5(8):1701-6. Epub 2007 May 21. Pubmed
  4. Montes R, Ruiz de Gaona E, Martinez-Gonzalez MA, Alberca I, Hermida J: The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients. Br J Haematol. 2006 Apr;133(2):183-7. Pubmed
  5. Rettie AE, Farin FM, Beri NG, Srinouanprachanh SL, Rieder MJ, Thijssen HH: A case study of acenocoumarol sensitivity and genotype-phenotype discordancy explained by combinations of polymorphisms in VKORC1 and CYP2C9. Br J Clin Pharmacol. 2006 Nov;62(5):617-20. Epub 2006 Jul 21. Pubmed
  6. Schalekamp T, Brasse BP, Roijers JF, Chahid Y, van Geest-Daalderop JH, de Vries-Goldschmeding H, van Wijk EM, Egberts AC, de Boer A: VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects overanticoagulation. Clin Pharmacol Ther. 2006 Jul;80(1):13-22. Pubmed
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Stehle S, Kirchheiner J, Lazar A, Fuhr U: Pharmacogenetics of oral anticoagulants: a basis for dose individualization. Clin Pharmacokinet. 2008;47(9):565-94. Pubmed
  3. Bodin L, Verstuyft C, Tregouet DA, Robert A, Dubert L, Funck-Brentano C, Jaillon P, Beaune P, Laurent-Puig P, Becquemont L, Loriot MA: Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity. Blood. 2005 Jul 1;106(1):135-40. Epub 2005 Mar 24. Pubmed
  4. Gonzalez-Conejero R, Corral J, Roldan V, Ferrer F, Sanchez-Serrano I, Sanchez-Blanco JJ, Marin F, Vicente V: The genetic interaction between VKORC1 c1173t and calumenin a29809g modulates the anticoagulant response of acenocoumarol. J Thromb Haemost. 2007 Aug;5(8):1701-6. Epub 2007 May 21. Pubmed
  5. Montes R, Ruiz de Gaona E, Martinez-Gonzalez MA, Alberca I, Hermida J: The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients. Br J Haematol. 2006 Apr;133(2):183-7. Pubmed
  6. Rettie AE, Farin FM, Beri NG, Srinouanprachanh SL, Rieder MJ, Thijssen HH: A case study of acenocoumarol sensitivity and genotype-phenotype discordancy explained by combinations of polymorphisms in VKORC1 and CYP2C9. Br J Clin Pharmacol. 2006 Nov;62(5):617-20. Epub 2006 Jul 21. Pubmed
  7. Schalekamp T, Brasse BP, Roijers JF, Chahid Y, van Geest-Daalderop JH, de Vries-Goldschmeding H, van Wijk EM, Egberts AC, de Boer A: VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects overanticoagulation. Clin Pharmacol Ther. 2006 Jul;80(1):13-22. Pubmed
  8. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

3. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

4. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. Pubmed
  2. Morales-Molina JA, Arrebola MA, Robles PA, Mangana JC: Possible interaction between topical terbinafine and acenocoumarol. Ann Pharmacother. 2009 Nov;43(11):1911-2. Epub 2009 Oct 20. Pubmed

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: no

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. Fitos I, Visy J, Simonyi M, Hermansson J: Stereoselective distribution of acenocoumarol enantiomers in human plasma: chiral chromatographic analysis of the ultrafiltrates. Chirality. 1993;5(5):346-9. Pubmed
  2. Fitos I, Visy J, Magyar A, Kajtar J, Simonyi M: Inverse stereoselectivity in the binding of acenocoumarol to human serum albumin and to alpha 1-acid glycoprotein. Biochem Pharmacol. 1989 Jul 15;38(14):2259-62. Pubmed
  3. Otagiri M, Fleitman JS, Perrin JH: Investigations into the binding of phenprocoumon to albumin using fluorescence spectroscopy. J Pharm Pharmacol. 1980 Jul;32(7):478-82. Pubmed

2. Alpha-1-acid glycoprotein 1

Kind: protein

Organism: Human

Pharmacological action: no

Components

Name UniProt ID Details
Alpha-1-acid glycoprotein 1 P02763 Details

References:

  1. Fitos I, Visy J, Simonyi M, Hermansson J: Stereoselective distribution of acenocoumarol enantiomers in human plasma: chiral chromatographic analysis of the ultrafiltrates. Chirality. 1993;5(5):346-9. Pubmed
  2. Fitos I, Visy J, Magyar A, Kajtar J, Simonyi M: Inverse stereoselectivity in the binding of acenocoumarol to human serum albumin and to alpha 1-acid glycoprotein. Biochem Pharmacol. 1989 Jul 15;38(14):2259-62. Pubmed
  3. Hazai E, Visy J, Fitos I, Bikadi Z, Simonyi M: Selective binding of coumarin enantiomers to human alpha1-acid glycoprotein genetic variants. Bioorg Med Chem. 2006 Mar 15;14(6):1959-65. Epub 2005 Nov 15. Pubmed

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Drug created on July 24, 2007 02:32 / Updated on March 26, 2014 16:06