Identification

Name Warfarin

Accession Number DB00682 (APRD00341)

Type small molecule

Groups approved

Description

Warfarin is an anticoagulant drug normally used to prevent blood clot formation as well as migration. Although originally marketed as a pesticide (d-Con, Rodex, among others), Warfarin has since become the most frequently prescribed oral coagulant in North America. Warfarin has several properties that should be noted when used medicinally, including its ability to cross the placental barrier during pregnancy which can result in fetal bleeding, spontaneous abortion, preterm birth, stillbirth, and neonatal death. Additional adverse effects such as necrosis, purple toe syndrome, osteoporosis, valve and artery calcification, and drug interactions have also been documented with warfarin use. Warfarin does not actually affect blood viscosity, rather, it inhibits vitamin-k dependent synthesis of biologically active forms of various clotting factors in addition to several regulatory factors.

Structure

 Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure 

Synonyms Warfarin sodium

Salts Not Available

Brand names

Name

Athrombin

Athrombin-K

Athrombine-K

Brumolin

Co-Rax

Coumadin

Coumadin Tabs

Coumafen

Coumafene

Coumaphen

                                          

Brand mixtures Not Available

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Categories

Anticoagulants Rodenticides Coumarin and Indandione Derivatives

CAS number 81-81-2

Weight Average: 308.3279Monoisotopic: 308.104859

Chemical Formula C19H16O4

InChI Key InChIKey=PJVWKTKQMONHTI-UHFFFAOYSA-N

InChI 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,11H2,1H3Plain Text

IUPAC Name 4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H-chromen-2-one

SMILES CC(=O)CC(C1=CC=CC=C1)C1=C(O)C2=C(OC1=O)C=CC=C2Plain Text

Mass Spec show (8.72 KB)

Taxonomy

Kingdom Not Available

Classes Not Available

Substructures Not Available

Pharmacology

Indication For the treatment of retinal vascular occlusion, pulmonary embolism, cardiomyopathy, atrial fibrillation and flutter, cerebral embolism, transient cerebral ischaemia, arterial embolism and thrombosis.

Pharmacodynamics

Warfarin, a coumarin anticoagulant, is a racemic mixture of two active isomers. It is used in 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).

Mechanism of action

Warfarin 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 proteins, 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. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.

Absorption Rapidly absorbed following oral administration with considerable interindividual variations.

Volume of distribution

0.14 L/kg

Protein binding 99% bound primarily to albumin

Metabolism Metabolized stereo- and regio-selectively by hepatic microsomal enzymes. S-warfarin is predominantly metabolized by cytochrome P450 (CYP) 2C9 to yield the 6- and 7-hydroxylated metabolites. R-warfarin is metabolized by CYP1A1, 1A2, and 3A4 to yield 6-, 8-, and 10-hydroxylated metabolites. Hydroxylated metabolites may be further conjugated prior to excretion into bile and urine. UGT1A1 appears to be responsible for producing the 6-O-glucuronide of warfarin, with a possibly contribution from UGT1A10. Five UGT1As may be involved in the formation of 7-O-glucuronide warfarin. S-warfarin has higher potency than R-warfarin and genetic polymorphisms in CYP2C9 may dramatically decrease clearance of and increase toxicity of the medication.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please

Substrate Enzymes Product

Warfarin Cytochrome P450 2C9

S-6-Hydroxywarfarin

Warfarin

Cytochrome P450 2C8 Cytochrome P450 2C18 Cytochrome P450 2C19 S-4'-Hydroxywarfarin

Warfarin Cytochrome P450 2C9 Cytochrome P450 2C18 R-4'-Hydroxywarfarin

Warfarin

Cytochrome P450 2C19 Cytochrome P450 1A1 Cytochrome P450 1A2 R-6-Hydroxywarfarin

Warfarin Cytochrome P450 3A4

R-10-Hydroxywarfarin

Warfarin

Cytochrome P450 1A1 Cytochrome P450 1A2 Cytochrome P450 2C19 R-8-Hydroxywarfarin

Warfarin

Cytochrome P450 1A1 Cytochrome P450 1A2 Cytochrome P450 2C8 R-7-Hydroxywarfarin

Warfarin dehydrowarfarin

Route of elimination

The elimination of warfarin is almost entirely by metabolism. Very little warfarin is excreted unchanged in urine. The metabolites are principally excreted into the urine; and to a lesser extent into the bile.

Half life R-warfarin t1/2=37-89 hours; S-warfarin t1/2=21-43 hours.

Clearance

0.065 +/- 0.025 mL/min/kg [CYP2C9 Genotype 1/1] 0.041 +/- 0.021 [CYP2C9 Genotype 1/2 or 1/3] 0.020 +/- 0.011 [CYP2C9 Genotype 2/2, 2/3, or 3/3]

Toxicity LD50=374 (orally in mice)

Affected organisms Humans and other mammals

Pathways

Pathway Name

Warfarin Pathway

Pharmacoeconomics

Manufacturers Pharmaceutical research assoc inc Bristol myers squibb pharma co Usl pharma inc Abbott laboratories pharmaceutical products div

Barr laboratories inc Mylan pharmaceuticals inc Pliva inc Sandoz inc Taro pharmaceuticals inc Watson laboratories inc Zydus pharmaceuticals usa inc

Packagers Advanced Pharmaceutical Services Inc. Amerisource Health Services Corp. Apothecon AQ Pharmaceuticals Inc. A-S Medication Solutions LLC Atlantic Biologicals Corporation Barr Pharmaceuticals Blenheim Pharmacal Bristol-Myers Squibb Co. Cadila Healthcare Ltd. Cardinal Health Caremark LLC Coastal Family Health Center Inc. Dept Health Central Pharmacy Direct Dispensing Inc. Dispensing Solutions Diversified Healthcare Services Inc. Genpharm LP Heartland Repack Services LLC Ipca Laboratories Ltd. Kaiser Foundation Hospital Lake Erie Medical and Surgical Supply Mallinckrodt Inc. Murfreesboro Pharmaceutical Nursing Supply Mylan Neuman Distributors Inc. Nucare Pharmaceuticals Inc. Palmetto Pharmaceuticals Inc. PCA LLC PD-Rx Pharmaceuticals Inc. Pharmaceutical Utilization Management Program VA Inc. Pharmedix Physicians Total Care Inc. Pliva Inc. Prepackage Specialists Prepak Systems Inc. Rebel Distributors Corp. Remedy Repack Resource Optimization and Innovation LLC Sandhills Packaging Inc. Southwood Pharmaceuticals Spectrum Pharmaceuticals St Mary's Medical Park Pharmacy Stat Scripts LLC Taro Pharmaceuticals USA Tya Pharmaceuticals Upsher Smith Laboratories USL Pharma Inc. Va Cmop Dallas Vangard Labs Inc.

Zydus Pharmaceuticals

Dosage forms

Form Route

Tablet Oral 1 mg

Tablet Oral 10 mg

Tablet Oral 2 mg

Tablet Oral 2.5 mg

Tablet Oral 3 mg

Tablet Oral 4 mg

Tablet Oral 5 mg

Tablet Oral 6 mg

Tablet Oral 7.5 mg

Prices

Unit description Cost

Warfarin sodium powder 54.53 USD

Coumadin 5 mg vial 34.07 USD

Coumadin 10 mg tablet 2.01 USD

Coumadin 7.5 mg tablet 1.97 USD

Coumadin 6 mg tablet 1.94 USD

Coumadin 3 mg tablet 1.51 USD

Coumadin 5 mg tablet 1.51 USD

Coumadin 4 mg tablet 1.49 USD

Coumadin 2.5 mg tablet 1.46 USD

Coumadin 2 mg tablet 1.4 USD

                                          DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents Not Available

Properties

State solid

Experimental Properties

Property Value

melting point 161 °C

water solubility 17 mg/L (at 20 °C)

logP 2.70

logS -3.89

Caco2 permeability -4.68

pKa 5.08

10

Predicted Properties

Property Value

water solubility 4.72e-02 g/l

logP 2.41

logP 2.74

logS -3.8

pKa (strongest acidic) 6.33

pKa (strongest basic) -6.6

physiological charge -1

hydrogen acceptor count 3

hydrogen donor count 1

polar surface area 63.6

rotatable bond count 4

refractivity 86.86

polarizability 31.98

References

Synthesis Reference Not Available

General Reference

1. Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E: The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):204S-233S.

2. Whitlon DS, Sadowski JA, Suttie JW: Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. 1978 Apr 18;17(8):1371-7. Pubmed

3. Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW: Identification of the gene for vitamin K epoxide reductase. 5;427(6974):541-4. Pubmed

4. Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hortnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, Muller CR, Strom TM, Oldenburg J: Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Feb 5;427(6974):537-41. Pubmed

5. Hirsh J, Fuster V, Ansell J, Halperin JL: American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol. 2003 May 7;41(9):1633-52. Pubmed

6. Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M, Wells PS: Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005 May 23;165(10):1095-106. Pubmed

7. Macina, Orest T.; Schardein, James L. (2007). “Warfarin”. Human Developmental Toxicants. Boca Raton:4

8. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G: Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):160S-198S. doi: 10.1378/chest.08-0670. Pubmed

9. Freedman MD: Oral anticoagulants: pharmacodynamics, clinical indications and adverse effects. 209. Pubmed

10. Loftus, Christopher M. (1995). “Fetal toxicity of common neurosurgical drugs”. Neurosurgical Aspects of Pregnancy. Park Ridge, Ill: American Association of Neurological Surgeons. pp. 11–3.

External Links Resource Link

KEGG Compound C01541  

BindingDB 50088240  

ChEBI 10033  

ChEMBL 10033  

Therapeutic Targets Database DAP000770  

PharmGKB PA451906  

Drug Product Database 2244463  

RxList http://www.rxlist.com/cgi/generic/warfarin.htm

Drugs.com http://www.drugs.com/warfarin.html  

Wikipedia http://en.wikipedia.org/wiki/Warfarin  

ATC Codes B01AA03

AHFS Codes 20:12.04.08

PDB Entries Not Available

FDA label show (641 KB)

MSDS show (59.5 KB)

Interactions

Drug Interactions Drug Interaction

Acetaminophen Acetaminophen increases the anticoagulant effect of warfarin. Monitor for changes in the therapeutic and adverse effects of warfarin if acetaminophen is initiated, discontinued or dose changed.

Acetylsalicylic acid The antiplatelet effects of acetylsalicylic acid may increase the bleed risk associated with warfarin.

Allopurinol Allopurinol may increase the anticoagulant effect of warfarin. Monitor for changes in prothrombin times and therapeutic effects of warfarin if allopurinol is initiated, discontinued or dose changed.

Aminoglutethimide Aminoglutethimide may decrease the anticoagulant effect of warfarin by increasing its metabolism. Monitor for changes in prothrombin time and therapeutic effects of warfarin if aminoglutethimide is initiated, discontinued or dose changed.

Aminosalicylic Acid The antiplatelet effects of aminosalicylic acid may increase the bleed risk associated with warfarin.

Amiodarone Amiodarone may increase the anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if amiodarone is initiated, discontinued or dose changed.

Amobarbital Amobarbital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if amobarbital is initiated, discontinued or dose changed.

Amprenavir Amprenavir may increase the anticoagulant effect of warfarin by increasing its serum concentration.

Aprepitant Aprepitant may decrease the anticoagulant effect of warfarin by decreasing its serum concentration.

Atazanavir The protease inhibitor, atazanavir, may increase the anticoagulant effect of warfarin.

Avanafil Co-administration with avanafil resulted in an approximate 1.6% increase in AUC(0-inf) and 5.2% decrease in Cmax of S-warfarin.

Azathioprine Azathioprine may decrease the anticoagulant effect of warfarin.

Azithromycin Azithromycin may increase the anticoagulant effect of warfarin by increasing its serum concentration.

Betamethasone The corticosteroid, betamethasone, alters the anticoagulant effect of warfarin.

Bezafibrate Bezafibrate may increase the anticoagulant effect of warfarin. Monitor prothrombin time and therapeutic and adverse effects of warfarin if bezafibrate is initiated, discontinued or dose changed.

Bosentan Bosentan may decrease the anticoagulant effect of warfarin by increasing its metabolism.

Butabarbital Butabarbital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if butabarbital is initiated, discontinued or dose changed.

Butalbital Butalbital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if butalbital is initiated, discontinued or dose changed.

CapecitabineCapecitabine may increase the serum concentration of warfarin by decreasing its metabolism. Monitor for changes in prothrombin time and therapeutic effects of warfarin if capecitabine is initiated or discontinued. capecitabine may increase this effect.

Carbamazepine Carbamazepine may decrease the anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic and adverse effects of warfarin if carbamazepine is initiated, discontinued or dose changed.

Cefotetan The cephalosporin, cefotetan, may increase the anticoagulant effect of warfarin.

Cefoxitin The cephalosporin, cefoxitin, may increase the anticoagulant effect of warfarin.

Ceftriaxone The cephalosporin, ceftriaxone, may increase the anticoagulant effect of warfarin.

Celecoxib Celecoxib may increase the anticoagulant effect of warfarin.

Cholestyramine The bile acid sequestrant, cholestyramine, may decrease the anticoagulant effect of warfarin by decreasing its absorption.

Cimetidine Cimetidine may increase the serum concentration of warfarin. Monitor for changes in prothrombin time and therapeutic and adverse effects of warfarin if cimetidine is initiated, discontinued or dose changed.

Ciprofloxacin The quinolone antibiotic, ciprofloxacin, may increase the anticoagulant effect of warfarin.

Cisapride Cisapride may increase the anticoagulant effect of warfarin.

Citalopram The SSRI, citalopram, increases the effect of anticoagulant, warfarin.

Clarithromycin The macrolide, clarithromycin, may increase the anticoagulant effect of warfarin.

Clofibrate The fibrate increases the anticoagulant effect

Clopidogrel Increased bleed risk may occur as a result of additive anticoagulant effects. Increase monitoring for signs and symptoms of bleeding during concomitant therapy.

Colestipol The bile acid sequestrant, colestipol, may decrease the anticoagulant effect of warfarin by decreasing its absorption.

Cyclophosphamide The antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of warfarin.

Danazol Danazol may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if danazol is initiated, discontinued or dose changed.

Delavirdine Delavirdine, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if delavirdine is initiated, discontinued or dose changed.

Demeclocycline The tetracycline, demeclocycline, may increase the anticoagulant effect of warfarin.

Desogestrel Desogestrol may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if desogestrol is initiated, discontinued or dose changed.

Dexamethasone The corticosteroid, dexamethasone, alters the anticoagulant effect of warfarin.

Dextrothyroxine The thyroid hormone, dextrothyroxine, increase the anticoagulant effect of warfarin.

Diclofenac The antiplatelet effects of oral diclofenac may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.

Dicloxacillin Dicloxacillin may decrease the anticoagulant effect of warfarin.

Diflunisal The antiplatelet effects of diflunisal may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.

Disulfiram Disulfiram may increase the anticoagulant effect of warfarin.

Doxycycline The tetracycline, doxycycline, may increase the anticoagulant effect of warfarin.

Dronedarone Dronedarone is a moderate inhibitor of CYP3A4 which is responsible for warfarin metabolism. concentration of S-isomer warfarin by 1.2 fold

Drospirenone Drospirenone may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if drospirenone is initiated, discontinued or dose changed.

Drotrecogin alfa Increased risk of bleeding.

Erythromycin The macrolide, erythromycin, may increase the anticoagulant effect of warfarin.

Ethchlorvynol Ethchlorvynol may decrease the anticoagulant effect of warfarin.

Ethinyl Estradiol Ethinyl estradiol may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if ethinyl estradiol is initiated, discontinued or dose changed.

Ethynodiol Diacetate Ethynodiol diacetate may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if ethynodiol diacetate is initiated, discontinued or dose

Etodolac The antiplatelet effects of etodolac may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.

Etonogestrel Etonogestrel may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if etonogestrel is initiated, discontinued or dose changed.

Etoricoxib Etoricoxib may increase the anticoagulant effect of warfarin.

Ezetimibe If ezetimibe is added to warfarin, a coumarin anticoagulant, the International Normalized Ratio (INR) should be appropriately monitored.

F decreases the effect of cortisone by metabolism alteration.

Fenofibrate Fenofibrate may increase the anticoagulant effect of warfarin. Monitor prothrombin time and therapeutic and adverse effects of warfarin if fenofibrate is initiated, discontinued or dose changed.

Fenoprofen The antiplatelet effects of fenoprofen may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.

Floxuridine Floxuridine, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if floxuridine is initiated, discontinued or dose changed.

Fluconazole Fluconazole, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if fluconazole is initiated, discontinued or dose changed.

Fludrocortisone The corticosteroid, fludrocortisone, alters the anticoagulant effect of warfarin.

Fluorouracil Fluorouracil, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if fluorouracil is initiated, discontinued or dose changed.

Fluoxetine The SSRI, fluoxetine, increases the effect of anticoagulant, warfarin.

Fluoxymesterone Fluoxymesterone may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if fluoxymesterone is initiated, discontinued or dose changed.

FlurbiprofenFlurbiprofen, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. The antiplatelet effect of flurbiprofen may also increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if flurbiprofen is initiated, discontinued or dose changed.

Fluvastatin Fluvastatin may increase the anticoagulant effect of warfarin. Monitor for changes in the therapeutic and adverse effects of warfarin if fluvastatin is initiated, discontinued or dose changed.

Fluvoxamine Fluvoxamine may increase the anticoagulant effect of warfarin by increasing its serum concentration.

Fosamprenavir The protease inhibitor, fosamprenavir, may increase the anticoagulant effect of warfarin.

Fosphenytoin Increased hydantoin levels and risk of bleeding

Gadofosveset trisodium

In a clinical trial of 10 patients receiving a stable dose of warfarin, a single dose of ABLAVAR (0.05 mmol/kg) did not alter the anticoagulant activity of warfarin as measured by the International Normalized Ratio (INR).

Gefitinib Gefitinib may increase the anticoagulant effect of warfarin.

Gemcitabine Gemcitabine may increase the anticoagulant effect of warfarin.

Gemfibrozil Gemfibrozil, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if gemfibrozil is initiated, discontinued or dose changed.

Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.

Ginseng Additive anticoagulant effects increase the risk of bleeding. Concomitant therapy should be avoided.

GlutethimideGlutethimide may decrease the serum concentration of warfarin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if glutethimide is initiated, discontinued or dose changed.

Griseofulvin Griseofulvin may decrease the anticoagulant effect of warfarin.

HomoharringtonineAvoid combination with warfarin and other anticoagulants due to the potential enhancement of homoharringtonine associated bleeding-related adverse effects. Specifically it is suggested to avoid this combination in patients with a platelet count of less than 50,000/uL.

Hydrocortisone The corticosteroid, hydrocortisone, alters the anticoagulant effect of warfarin.

IbuprofenIbuprofen, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. The antiplatelet effect of ibuprofen may also increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if ibuprofen is initiated, discontinued or dose changed.

Imatinib Imatinib may increase the anticoagulant effect of warfarin increasing the risk of bleeding. Monitor for changes in prothrombin time and therapeutic and adverse effects of warfarin if imatinib is initiated, discontinued or dose changed.

Indinavir The protease inhibitor, indinavir, may increase the anticoagulant effect of warfarin.

IndomethacinIndomethacin, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. The antiplatelet effect of indomethacin may also increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if indomethacin is initiated, discontinued or dose changed.

Isoniazid Isoniazid may increase the anticoagulant effect of warfarin.

Itraconazole Itraconazole may increase the anticoagulant effect of warfarin by decreasing its metabolism.

Ketoconazole Ketoconazole, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if ketoconazole is initiated, discontinued or dose changed.

Ketoprofen The antiplatelet effects of ketoprofen may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.

Ketorolac The antiplatelet effects of ketorolac may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.

Leflunomide Leflunomide may increase the anticoagulant effect of warfarin.

Levamisole Levamisole may increase the anticoagulant effect of warfarin.

Levofloxacin The quinolone antibiotic, levofloxacin, may increase the anticoagulant effect of warfarin.

Levonorgestrel Levonorgestrel may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if levonorgestrel is initiated, discontinued or dose changed.

LevothyroxineLevothyroxine may contribute to the anticoagulant effect of warfarin by increasing the metabolism of vitamin K-dependent clotting factors. Monitor for changes in prothrombin time and anticoagulant effects if levothyroxine is initiated, discontinued or dose changed.

LiothyronineLiothyronine may contribute to the anticoagulant effect of warfarin by increasing the metabolism of vitamin K-dependent clotting factors. Monitor for changes in prothrombin time and anticoagulant effects if liothyronine is initiated, discontinued or dose changed.

LiotrixLiotrix may contribute to the anticoagulant effect of warfarin by increasing the metabolism of vitamin K-dependent clotting factors. Monitor for changes in prothrombin time and anticoagulant effects if liotrix is initiated, discontinued or dose changed.

Lomitapide Warfarin plasma concentrations may increase by lomitapide by 30%.. INR levels may increase by 22%. Regular INR monitoring is required.

Lovastatin Lovastatin may increase the anticoagulant effect warfarin. Monitor for changes in the therapeutic and adverse effects of warfarin if lovastatin is initiated, discontinued or dose changed .

Lumiracoxib Lumiracoxib may increase the anticoagulant effect of warfarin.

Meclofenamic acid The antiplatelet effects of meclofenamic acid may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.

Medroxyprogesterone

Medroxyprogesterone may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if medroxyprogesterone is initiated, discontinued or dose changed.

Mefenamic acidMefenamic acid, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. The antiplatelet effect of mefenamic acid may also increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if mefenamic acid is initiated, discontinued or dose changed.

Mefloquine Mefloquine may increase the anticoagulant effect of warfarin.

Meloxicam The antiplatelet effects of meloxicam may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.

Mercaptopurine Mercaptopurine may decrease the anticoagulant effect of warfarin.

Mestranol Mestranol may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if mestranol is initiated, discontinued or dose changed.

Methimazole Methimazole may decrease the anticoagulant effect of warfarin. Monitor for changes in the therapeutic and adverse effects of warfarin if methimazole is initiated, discontinued or dose changed.

Methohexital Methohexital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if methohexital is initiated, discontinued or dose changed.

MetronidazoleMetronidazole may increase the serum concentration of warfarin by decreasing its metabolism. Consider alternate therapy or a dose reduction in warfarin. Monitor for changes in prothrombin time and therapeutic and adverse effects of warfarin if metronidazole is initiated, discontinued or dose changed.

Miconazole Miconazole, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if miconazole is initiated, discontinued or dose changed.

Minocycline The tetracycline, minocycline, may increase the anticoagulant effect of warfarin.

Mirabegron Mirabegron increased Cmax and AUC of S- and R-warfarin. Monitor concomitant therapy closely.

Mitotane Mitotane may decrease the anticoagulant effect of warfarin.

Moxifloxacin The quinolone antibiotic, moxifloxacin, may increase the anticoagulant effect of warfarin.

Nabumetone The antiplatelet effects of nabumetone may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.

Nafcillin Nafcillin may increase the anticoagulant effect of warfarin increasing the risk of bleeding. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if nafcillin is initiated, discontinued or dose changed.

Nalidixic Acid The quinolone antibiotic, nalidixic acid, may increase the anticoagulant effect of warfarin.

Nandrolone decanoate

Nandrolone may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if nandrolone is initiated, discontinued or dose changed.

Nandrolone phenpropionate

Nandrolone may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if nandrolone is initiated, discontinued or dose changed.

Naproxen The antiplatelet effects of naproxen may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.

Nelfinavir The protease inhibitor, nelfinavir, may increase the anticoagulant effect of warfarin.

Nevirapine Nevirapine may decrease the anticoagulant effect of warfarin by increasing metabolism of R-warfarin via CYP3A4.

Nicardipine Nicardipine, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if nicardipine is initiated, discontinued or dose changed.

Norethindrone Norethindrone may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if norethindrone is initiated, discontinued or dose changed.

Norfloxacin The quinolone antibiotic, norfloxacin, may increase the anticoagulant effect of warfarin.

Norgestimate Norgestimate may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if norgestimate is initiated, discontinued or dose changed.

Ofloxacin The quinolone antibiotic, ofloxacin, may increase the anticoagulant effect of warfarin.

Orlistat Orlistat may increase the anticoagulant effect of warfarin.

Oxandrolone Oxandrolone may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if oxandrolone is initiated, discontinued or dose changed.

Oxaprozin The antiplatelet effects of oxaprozin may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.

oxymetholone Oxymetholone may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if oxymetholone is initiated, discontinued or dose changed.

Oxyphenbutazone The NSAID, oxyphenbutazone, may increase the anticoagulant effect of warfarin.

Paroxetine The SSRI, paroxetine, increases the effect of the anticoagulant, warfarin.

Pentobarbital Pentobarbital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if pentobarbital is initiated, discontinued or dose changed.

Pentoxifylline Pentoxifylline may increase the anticoagulant effect of warfarin.

Phenobarbital Phenobarbital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if phenobarbital is initiated, discontinued or dose changed.

Phenylbutazone The NSAID, phenylbutazone, may increase the anticoagulant effect of warfarin.

PhenytoinWarfarin may increase the serum concentration of phenytoin possibly by competing for CYP2C9 metabolism. Phenytoin may increase the anticoagulant effect of warfarin. Monitor phenytoin levels, prothrombin time, and therapeutic and adverse effects of both agents during concomitant therapy.

Phytonadione Phytonadione (vitamin K) may antagonize the anticoagulant effects of warfarin. Monitor for changes in prothrombin time if phytonadione intake (either via supplements or vitamin K-rich foods) is increased or decreased.

PiroxicamPiroxicam, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. The antiplatelet effect of piroxicam may also increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if piroxicam is initiated, discontinued or dose changed.

Prasugrel Coadministration with warfarin may increase the risk of bleeding.

Prednisolone The corticosteroid, prednisolone, alters the anticoagulant effect of warfarin.

Prednisone The corticosteroid, prednisone, alters the anticoagulant effect of warfarin.

Primidone The barbiturate, primidone, decreases the anticoagulant effect of warfarin.

Propafenone Propafenone may increase the anticoagulant effect of warfarin.

Propoxyphene Propoxyphene may increase the anticoagulant effect of warfarin.

Propylthiouracil Propylthiouracil may decrease the anticoagulant effect of warfarin. Monitor for changes in the therapeutic and adverse effects of warfarin if propylthiouracil is initiated, discontinued or dose changed.

Quinidine Quinidine may increase the anticoagulant effect of warfarin.

Quinine Quinine, a moderate CYP2C9 inhibitor, may increase the serum concentration of S-warfarin by decreasing its metabolism via CYP2C9.

Ranitidine Ranitidine may increase the anticoagulant effect of warfarin. (Conflicting evidence)

Rifabutin Rifabutin may decrease the anticoagulant effect of warfarin by increasing its metabolism.

Rifampin Rifampin may decrease the anticoagulant effect of warfarin by increasing its metabolism.

S-Adenosylmethionine Additive anticoagulant effects increase the risk of bleeding. Concomitant therapy should be avoided.

Salicylate-sodium The antiplatelet effects of sodium salicylate may increase the bleed risk associated with warfarin.

Secobarbital Secobarbital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if secobarbital is initiated, discontinued or dose changed.

SitaxentanSitaxentan, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Warfarin doses should be decreased by 80% upon initiated of concomitant therapy. Monitor for changes in the therapeutic and adverse effects of warfarin if sitaxentan is initiated, discontinued or dose changed.

St. John's WortSt. John's Wort may decrease the serum concentration of warfarin by increasing its metabolism. Concomitant therapy should be avoided. Monitor for changes in the therapeutic and adverse effects of warfarin if St. John's Wort is initiated, discontinued or dose changed.

Sucralfate Sucralfate may reduce the absorption of warfarin. Warfarin should be administered at least 2 hours before or 6 hours after sucralfate administration. Monitor for changes in prothrombin time if sucralfate is initiated, discontinued or dose changed.

Sulfadiazine Sulfadiazine, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if sulfadiazine is initiated, discontinued or dose changed.

Sulfamethoxazole Sulfamethoxazole may increase the anticoagulant effect of warfarin by decreasing its metabolism. Consider alternate therapy or monitor for changes in prothrombin time if sulfamethoxazole is initiated, discontinued or dose changed.

Sulfinpyrazone Sulfinpyrazone may increase the anticoagulant effect of warfarin by decreasing its metabolism and protein binding.

Sulfisoxazole Sulfisoxazole, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if sulfisoxazole is initiated, discontinued or dose changed.

Sulindac The antiplatelet effects of sulindac may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.

Tamoxifen Tamoxifen, a CYP2C9 inhibitor, may increase the serum concentration of warfarin by decreasing its metabolism. Concomitant therapy is contraindicated due to significant increase in bleed risk.

Telithromycin Telithromycin may increase the anticoagulant effect of Warfarin. INR should be monitored and Warfarin dose adjusted accordingly during concomitant therapy.

Tenoxicam The NSAID, tenoxicam, may increase the anticoagulant effect of warfarin.

Testolactone Testolactone may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if testolactone is initiated, discontinued or dose changed.

Testosterone Testosterone may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if testosterone is initiated, discontinued or dose changed.

Testosterone Propionate

The androgen, Testosterone, may incrase the anticoagulant effect of the Vitamin K antagonist, Warfarin. Monitor for changes in the therapeutic effect of Warfarin if Testosterone is initiated, discontinued or dose changed.

Tetracycline Tetracycline may increase the anticoagulant effect of warfarin.

Thiopental Thiopental may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if thiopental is initiated, discontinued or dose changed.

Tiaprofenic acid The antiplatelet effects of tiaprofenic acid may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.

Ticlopidine Increased bleeding risk. Monitor INR.

Tigecycline Tigecycline may increase the serum concentration of warfarin.

Tolbutamide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if tolbutamide is initiated, discontinued or dose changed.

Tolmetin The antiplatelet effects of tolmetin may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.

transdermal testosterone gel

The androgen, Testosterone, may incrase the anticoagulant effect of the Vitamin K antagonist, Warfarin. Monitor for changes in the therapeutic effect of Warfarin if Testosterone is initiated, discontinued or dose changed.

Treprostinil The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the anticoagulant, Warfarin. Monitor for increased bleeding during concomitant thearpy.

Triamcinolone The corticosteroid, triamcinolone, alters the anticoagulant effect of warfarin.

TriflusalThe metabolite of triflusal, 2-hydroxy-4-trifluoro-methyl-benzoic acid (HTB), impairs the serum protein binding of warfarin to the same extent as acetylsalisylic acid. Thus, the free fraction of glisentide may be increased. A dosage reduction may be required if used in combination.

Trimetrexate The anticoagulant effect of Warfarin, 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.

Trisalicylate-choline The antiplatelet effects of trisalicylate-choline may increase the bleed risk associated with warfarin.

Vemurafenib Vemurafenib increases the AUC of S-warfarin (CYP2C9 substrate). Monitor concomitant therapy closely.

Vilazodone Increased risk of bleeding with concomitant use of warfarin and vilazodone.

Food Interactions

Avoid alcohol. Avoid drastic changes in dietary habit. Avoid St. John's Wort. Consult your doctor before ingesting large amounts of dietary Vitamin K (e.g. from green leafy vegetables). Limit garlic, ginger, gingko, and horse chestnut.

dentification

Name Ethyl biscoumacetate

Accession Number DB08794

Type small molecule

Groups

Description Ethyl biscoumacetate is a courmarin that is used as an anticoagulant. It has actions similar to those of Warfarin. (From Martindale, The Extra Pharmacopoeia, 30th ed, p226)

Structure

 Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure 

Synonyms Pelentan

Tromexan

Salts Not Available

Brand names Not Available

Brand mixtures Not Available

Categories Anticoagulants

CAS number 548-00-5

Weight Average: 408.3576Monoisotopic: 408.084517488

Chemical Formula C22H16O8

InChI Key InChIKey=SEGSDVUVOWIWFX-UHFFFAOYSA-N

InChIInChI=1S/C22H16O8/c1-2-28-20(25)15(16-18(23)11-7-3-5-9-13(11)29-21(16)26)17-19(24)12-8-4-6-10-14(12)30-22(17)27/h3-10,15,26-27H,2H2,1H3Plain Text

IUPAC Name ethyl 2,2-bis(2-hydroxy-4-oxo-4H-chromen-3-yl)acetate

SMILES CCOC(=O)C(C1=C(O)OC2=CC=CC=C2C1=O)C1=C(O)OC2=CC=CC=C2C1=OPlain Text

Mass Spec Not Available

Taxonomy

Kingdom Not Available

Classes Not Available

Substructures Not Available

Pharmacology

Indication Not Available

Pharmacodynamics Not Available

Mechanism of action Not Available

Absorption Not Available

Volume of distribution Not Available

Protein binding Not Available

Metabolism Not Available

Route of elimination Not Available

Half life Not Available

Clearance Not Available

Toxicity Not Available

Affected organisms Not Available

Pathways Not Available

Pharmacoeconomics

Manufacturers Not Available

Packagers Not Available

Dosage forms Not Available

Prices Not Available

Patents Not Available

Properties

State solid

Experimental Properties

Property Value Source

melting point 154 °C PhysProp

water solubility 153 mg/L (at 20 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)

Predicted Properties

Property Value

water solubility 8.61e-02 g/l

logP 2.18

logP 3.22

logS -3.7

pKa (strongest acidic) 7.13

pKa (strongest basic) -5.2

physiological charge 0

hydrogen acceptor count 7

hydrogen donor count 2

polar surface area 119.36

rotatable bond count 5

refractivity 123.2

polarizability 39.96

References

Synthesis Reference Not Available

General Reference Not Available

External Links

Resource Link

ChemSpider 10579  

ChEBI 231177  

ChEMBL 231177  

Wikipedia http://en.wikipedia.org/wiki/Ethyl_biscoumacetate  

ATC Codes B01AA08

AHFS Codes Not Available

PDB Entries Not Available

FDA label Not Available

MSDS Not Available

Interactions

Drug Interactions Not Available

Food Interactions Not Available