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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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Sintromtablet1 mgoralPaladin Labs IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Sintromtablet4 mgoralPaladin Labs IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
AscumarStar
Mini-sintromNot Available
SinkumarNot Available
Brand mixturesNot Available
SaltsNot 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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 4-hydroxycoumarins. These are coumarins that contain one or more hydroxyl groups attached to C4-position the coumarin skeleton.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassCoumarins and derivatives
Sub ClassHydroxycoumarins
Direct Parent4-hydroxycoumarins
Alternative Parents
Substituents
  • 4-hydroxycoumarin
  • 1-benzopyran
  • Benzopyran
  • Nitrobenzene
  • Pyranone
  • Benzenoid
  • Pyran
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Vinylogous acid
  • Organic nitro compound
  • Organic nitrite
  • C-nitro compound
  • Lactone
  • Ketone
  • Oxacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Allyl-type 1,3-dipolar organic compound
  • Organic oxoazanium
  • Hydrocarbon derivative
  • Organic salt
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Organic zwitterion
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
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
PropertyValueProbability
Human Intestinal Absorption+0.7518
Blood Brain Barrier+0.5765
Caco-2 permeable+0.5
P-glycoprotein substrateNon-substrate0.6031
P-glycoprotein inhibitor INon-inhibitor0.7078
P-glycoprotein inhibitor IINon-inhibitor0.843
Renal organic cation transporterNon-inhibitor0.8944
CYP450 2C9 substrateNon-substrate0.6256
CYP450 2D6 substrateNon-substrate0.8936
CYP450 3A4 substrateSubstrate0.6267
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 substrateInhibitor0.8949
CYP450 2D6 substrateNon-inhibitor0.9231
CYP450 2C19 substrateNon-inhibitor0.9026
CYP450 3A4 substrateNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7492
Ames testAMES toxic0.6954
CarcinogenicityNon-carcinogens0.7015
BiodegradationNot ready biodegradable0.9403
Rat acute toxicity2.7869 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6326
hERG inhibition (predictor II)Non-inhibitor0.9347
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tabletoral1 mg
Tabletoral4 mg
Prices
Unit descriptionCostUnit
Sintrom 4 mg Tablet1.6USD tablet
Sintrom 1 mg Tablet0.51USD tablet
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 Solubility0.0106 mg/mLALOGPS
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 Area109.42 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity94.18 m3·mol-1ChemAxon
Polarizability34.35 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
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
ATC CodesB01AA07
AHFS Codes
  • 20:12.04.08
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (126 KB)
Interactions
Drug Interactions
Drug
AbciximabAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
AcetaminophenMay enhance the anticoagulant effect of Vitamin K Antagonists. This appears most likely with daily acetaminophen doses exceeding 1.3 or 2 g/day for multiple consecutive days.
Acetylsalicylic acidAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
AllopurinolMay enhance the anticoagulant effect of Vitamin K Antagonists.
AlteplaseThrombolytic Agents may enhance the anticoagulant effect of Anticoagulants.
AmdinocillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
AminoglutethimideMay increase the metabolism of Vitamin K Antagonists.
Aminosalicylic AcidSalicylates may enhance the anticoagulant effect of Anticoagulants.
AmiodaroneMay enhance the anticoagulant effect of Vitamin K Antagonists. Amiodarone may increase the serum concentration of Vitamin K Antagonists.
AmoxicillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
AmpicillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
AnagrelideAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
AnistreplaseMay enhance the anticoagulant effect of Anticoagulants.
ApixabanMay enhance the anticoagulant effect of Anticoagulants.
ArgatrobanMay enhance the anticoagulant effect of other Anticoagulants.
AzathioprineMay diminish the anticoagulant effect of Vitamin K Antagonists.
AzidocillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
AzlocillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
BacampicillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
BenzylpenicillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
BicalutamideMay increase the serum concentration of Vitamin K Antagonists. Specifically, free concentrations of the vitamin K antagonists may be increased.
Bismuth SubsalicylateSalicylates may enhance the anticoagulant effect of Anticoagulants.
BivalirudinMay enhance the anticoagulant effect of other Anticoagulants.
BosentanMay increase the metabolism of Vitamin K Antagonists.
ButabarbitalMay increase the metabolism of Vitamin K Antagonists.
ButethalMay increase the metabolism of Vitamin K Antagonists.
CalcidiolMay diminish the anticoagulant effect of Vitamin K Antagonists.
CalcitriolMay diminish the anticoagulant effect of Vitamin K Antagonists.
CapecitabineMay increase the serum concentration of Vitamin K Antagonists.
CarbamazepineMay decrease the serum concentration of Vitamin K Antagonists.
CarbenicillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
CarbimazoleMay diminish the anticoagulant effect of Vitamin K Antagonists.
CefacetrileMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefaclorMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefadroxilMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefalotinMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefamandoleMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefapirinMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefazolinMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefdinirMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefditorenMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefepimeMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefiximeMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefmenoximeMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefmetazoleMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefonicidMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefoperazoneMay enhance the anticoagulant effect of Vitamin K Antagonists.
CeforanideMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefotaximeMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefotetanMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefotiamMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefoxitinMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefpiramideMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefpodoximeMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefprozilMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefradineMay enhance the anticoagulant effect of Vitamin K Antagonists.
Ceftaroline fosamilMay enhance the anticoagulant effect of Vitamin K Antagonists.
CeftazidimeMay enhance the anticoagulant effect of Vitamin K Antagonists.
CeftibutenMay enhance the anticoagulant effect of Vitamin K Antagonists.
CeftizoximeMay enhance the anticoagulant effect of Vitamin K Antagonists.
CeftobiproleMay enhance the anticoagulant effect of Vitamin K Antagonists.
CeftriaxoneMay enhance the anticoagulant effect of Vitamin K Antagonists.
CefuroximeMay enhance the anticoagulant effect of Vitamin K Antagonists.
CelecoxibNonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants.
CephalexinMay enhance the anticoagulant effect of Vitamin K Antagonists.
CephaloglycinMay enhance the anticoagulant effect of Vitamin K Antagonists.
Chloral hydrateMay increase the serum concentration of Vitamin K Antagonists.
ChloramphenicolMay enhance the anticoagulant effect of Vitamin K Antagonists. Chloramphenicol may increase the serum concentration of Vitamin K Antagonists.
CholecalciferolMay diminish the anticoagulant effect of Vitamin K Antagonists.
CilostazolAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
CimetidineMay enhance the anticoagulant effect of Vitamin K Antagonists.
CitalopramAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
Citric AcidMay enhance the anticoagulant effect of other Anticoagulants.
ClopidogrelAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
CloxacillinMay diminish the anticoagulant effect of Vitamin K Antagonists. Cloxacillin may enhance the anticoagulant effect of Vitamin K Antagonists.
ColesevelamMay decrease the absorption of Vitamin K Antagonists.
CyclacillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
Cyproterone acetateProgestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
Dabigatran etexilateMay enhance the anticoagulant effect of Anticoagulants.
DabrafenibMay decrease the serum concentration of CYP2C9 Substrates.
DalteparinMay enhance the anticoagulant effect of other Anticoagulants.
DanaparoidMay enhance the anticoagulant effect of other Anticoagulants.
DasatinibDasatinib may enhance the anticoagulant effect of Anticoagulants.
DeferasiroxMay increase the serum concentration of CYP1A2 Substrates.
Deoxycholic AcidAnticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased.
DesogestrelEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
DesvenlafaxineMay enhance the adverse/toxic effect of Vitamin K Antagonists. Specifically, the risk for bleeding may be increased.
DexmethylphenidateMay increase the serum concentration of Vitamin K Antagonists.
DicloxacillinMay diminish the anticoagulant effect of Vitamin K Antagonists.
DicoumarolMay enhance the anticoagulant effect of other Anticoagulants.
DiflunisalAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
DihydrotachysterolMay diminish the anticoagulant effect of Vitamin K Antagonists.
DihydrotestosteroneMay enhance the anticoagulant effect of Vitamin K Antagonists.
DipyridamoleAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
DisulfiramMay increase the serum concentration of Vitamin K Antagonists.
DronedaroneMay increase the serum concentration of Vitamin K Antagonists.
DrospirenoneEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
DuloxetineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
DydrogesteroneMay diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
EconazoleMay increase the serum concentration of Vitamin K Antagonists.
Edetic AcidMay enhance the anticoagulant effect of other Anticoagulants.
EfavirenzMay decrease the serum concentration of Vitamin K Antagonists. Efavirenz may increase the serum concentration of Vitamin K Antagonists.
EnoxaparinMay enhance the anticoagulant effect of other Anticoagulants.
EpoprostenolProstacyclin Analogues may enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination.
EptifibatideAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
ErgocalciferolMay diminish the anticoagulant effect of Vitamin K Antagonists.
EscitalopramAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
EsomeprazoleMay increase the serum concentration of Vitamin K Antagonists.
EstropipateEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
Ethacrynic acidMay increase the serum concentration of Vitamin K Antagonists.
Ethinyl EstradiolEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
EthotoinMay enhance the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may increase the serum concentration of Ethotoin.
Ethyl biscoumacetateMay enhance the anticoagulant effect of other Anticoagulants.
EthynodiolEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
EtodolacAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
EtonogestrelProgestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
EtoposideMay enhance the anticoagulant effect of Vitamin K Antagonists.
ExenatideMay enhance the anticoagulant effect of Vitamin K Antagonists.
FenoprofenAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
FloctafenineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
FlucloxacillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
FluconazoleMay increase the serum concentration of Vitamin K Antagonists.
FluoxetineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
FluvoxamineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
Fondaparinux sodiumMay enhance the anticoagulant effect of other Anticoagulants.
FosphenytoinMay enhance the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may increase the serum concentration of Fosphenytoin.
GefitinibMay enhance the anticoagulant effect of Vitamin K Antagonists.
GestodeneMay diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
Ginkgo bilobaMay enhance the adverse/toxic effect of Vitamin K Antagonists.
GlutethimideMay increase the metabolism of Vitamin K Antagonists.
GriseofulvinMay decrease the serum concentration of Vitamin K Antagonists.
HeparinMay enhance the anticoagulant effect of other Anticoagulants.
HeptabarbitalMay increase the metabolism of Vitamin K Antagonists.
HetacillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
HexobarbitalMay increase the metabolism of Vitamin K Antagonists.
HomoharringtonineMay enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased.
IbritumomabMay enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to an increased risk of bleeding.
IbuprofenAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
IcosapentOmega-3 Fatty Acids may enhance the anticoagulant effect of Anticoagulants.
Icosapent ethylOmega-3 Fatty Acids may enhance the anticoagulant effect of Anticoagulants.
IfosfamideMay enhance the anticoagulant effect of Vitamin K Antagonists.
IloprostProstacyclin Analogues may enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination.
IndomethacinAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
ItraconazoleMay increase the serum concentration of Vitamin K Antagonists.
KetoprofenAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
KetorolacAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
LansoprazoleMay increase the serum concentration of Vitamin K Antagonists.
LatamoxefMay enhance the anticoagulant effect of Vitamin K Antagonists.
LeflunomideMay enhance the anticoagulant effect of Vitamin K Antagonists.
LevomilnacipranMay enhance the adverse/toxic effect of Vitamin K Antagonists. Specifically, the risk for bleeding may be increased.
LevonorgestrelProgestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
Magnesium salicylateSalicylates may enhance the anticoagulant effect of Anticoagulants.
Medroxyprogesterone AcetateProgestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
Mefenamic acidAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
Megestrol acetateProgestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
MeloxicamAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
MercaptopurineMay diminish the anticoagulant effect of Vitamin K Antagonists.
MestranolEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
MethimazoleMay diminish the anticoagulant effect of Vitamin K Antagonists.
MethohexitalMay increase the metabolism of Vitamin K Antagonists.
MethylphenidateMay increase the serum concentration of Vitamin K Antagonists.
MeticillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
MezlocillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
MifepristoneMay increase the serum concentration of CYP2C9 Substrates.
MilnacipranMay enhance the adverse/toxic effect of Vitamin K Antagonists. Specifically, the risk for bleeding may be increased.
NabumetoneAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
NadroparinMay enhance the anticoagulant effect of other Anticoagulants.
NafcillinMay diminish the anticoagulant effect of Vitamin K Antagonists.
NaproxenAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
NeomycinMay enhance the anticoagulant effect of Vitamin K Antagonists.
NorelgestrominEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
NorethindroneProgestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
NorgestimateEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
ObinutuzumabAnticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.
OmeprazoleMay increase the serum concentration of Vitamin K Antagonists.
OritavancinMay increase the serum concentration of Vitamin K Antagonists.
OxacillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
OxandroloneMay enhance the anticoagulant effect of Vitamin K Antagonists.
OxaprozinAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
ParoxetineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
Peginterferon alfa-2bMay increase the serum concentration of CYP1A2 Substrates.
Penicillin VMay enhance the anticoagulant effect of Vitamin K Antagonists.
PentobarbitalMay increase the metabolism of Vitamin K Antagonists.
Pentosan PolysulfatePentosan Polysulfate Sodium may enhance the anticoagulant effect of Anticoagulants.
PentoxifyllineMay enhance the anticoagulant effect of Vitamin K Antagonists.
PhenindioneMay enhance the anticoagulant effect of other Anticoagulants.
PhenprocoumonMay enhance the anticoagulant effect of other Anticoagulants.
PhenytoinMay enhance the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may increase the serum concentration of Phenytoin.
PiperacillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
PiperazineEstrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects.
PiroxicamAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
PivampicillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
PivmecillinamMay enhance the anticoagulant effect of Vitamin K Antagonists.
PosaconazoleMay increase the serum concentration of Vitamin K Antagonists.
PrasugrelAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
PrimidoneMay increase the metabolism of Vitamin K Antagonists.
ProgesteroneProgestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects.
PropafenoneMay increase the serum concentration of Vitamin K Antagonists.
PropylthiouracilMay diminish the anticoagulant effect of Vitamin K Antagonists.
QuinidineMay enhance the anticoagulant effect of Vitamin K Antagonists. Note that the INR/PT might be unchanged in the face of increased bleeding.
QuinineMay enhance the anticoagulant effect of Vitamin K Antagonists.
ReteplaseThrombolytic Agents may enhance the anticoagulant effect of Anticoagulants.
RidogrelMay enhance the anticoagulant effect of Anticoagulants.
RivaroxabanAnticoagulants may enhance the anticoagulant effect of Rivaroxaban.
Salicylate-sodiumMay enhance the anticoagulant effect of Vitamin K Antagonists. Exceptions: Salsalate.
SalsalateSalicylates may enhance the anticoagulant effect of Anticoagulants.
SecobarbitalMay increase the metabolism of Vitamin K Antagonists.
SertralineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
StreptokinaseMay enhance the anticoagulant effect of Vitamin K Antagonists.
SucralfateMay diminish the anticoagulant effect of Vitamin K Antagonists. Sucralfate may decrease the serum concentration of Vitamin K Antagonists. Specifically, sucralfate may decrease the absorption of Vitamin K Antagonists.
SugammadexMay enhance the anticoagulant effect of Anticoagulants.
SulindacAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
SulodexideMay enhance the anticoagulant effect of other Anticoagulants.
TamoxifenMay increase the serum concentration of Vitamin K Antagonists.
TenecteplaseThrombolytic Agents may enhance the anticoagulant effect of Anticoagulants.
TeriflunomideMay decrease the serum concentration of CYP1A2 Substrates.
TestosteroneMay enhance the anticoagulant effect of Vitamin K Antagonists.
Tiaprofenic acidAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
TicagrelorAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
TicarcillinMay enhance the anticoagulant effect of Vitamin K Antagonists.
TiclopidineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
TinzaparinMay enhance the anticoagulant effect of other Anticoagulants.
TipranavirTipranavir may enhance the anticoagulant effect of Anticoagulants.
TirofibanAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
TolmetinAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
ToremifeneMay enhance the anticoagulant effect of Vitamin K Antagonists.
TositumomabMay enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse effects may be increased.
TramadolMay enhance the anticoagulant effect of Vitamin K Antagonists.
TreprostinilProstacyclin Analogues may enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination.
UrokinaseMay enhance the anticoagulant effect of Anticoagulants.
VemurafenibMay increase the serum concentration of CYP1A2 Substrates.
VenlafaxineAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
VilazodoneAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
Vitamin EVitamin E may enhance the anticoagulant effect of Anticoagulants. Vitamin E may also increase the overall risk for bleeding.
VorapaxarMay enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding.
VoriconazoleMay increase the serum concentration of Vitamin K Antagonists.
VorinostatMay enhance the anticoagulant effect of Vitamin K Antagonists.
WarfarinMay enhance the anticoagulant effect of other Anticoagulants.
ZafirlukastMay increase the serum concentration of Vitamin K Antagonists.
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