药品详细

Warfarin(华法林)

基本信息
剂型规格
适应症
药理
临床
理化性质
相互作用
文档
专利
Pathway
文献
序列

化学结构式图

中文名

华法林

英文名

Warfarin

分子式

C₁₉H₁₆O₄

化学名

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

分子量

Average: 308.3279
Monoisotopic: 308.104859

CAS号

81-81-2

ATC分类

B01A 抗血栓药

药物类型

small molecule

阶段

approved

商品名

同义名

基本介绍

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.

生产厂家

Abbott laboratories pharmaceutical products div
Barr laboratories inc
Bristol myers squibb pharma co
Mylan pharmaceuticals inc
Pharmaceutical research assoc inc
Pliva inc
Sandoz inc
Taro pharmaceuticals inc
Usl pharma inc
Watson laboratories inc
Zydus pharmaceuticals usa inc

封装厂家

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

参考

Synthesis Reference

Not Available

General Reference

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. Pubmed
Whitlon DS, Sadowski JA, Suttie JW: Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. Biochemistry. 1978 Apr 18;17(8):1371-7. Pubmed
Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW: Identification of the gene for vitamin K epoxide reductase. Nature. 2004 Feb 5;427(6974):541-4. Pubmed
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. Nature. 2004 Feb 5;427(6974):537-41. Pubmed
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
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
Macina, Orest T.; Schardein, James L. (2007). “Warfarin”. Human Developmental Toxicants. Boca Raton: CRC Taylor & Francis. pp. 193–4
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
Freedman MD: Oral anticoagulants: pharmacodynamics, clinical indications and adverse effects. J Clin Pharmacol. 1992 Mar;32(3):196-209. Pubmed
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.

剂型

规格

化合物类型

Type	small molecule

Classes

Not Available

Substructures

Not Available

适应症

药理

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. Also absorbed percutaneously.

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 contact us.

Substrate	Enzymes	Product
Warfarin	Cytochrome P450 2C9	S-6-Hydroxywarfarin	Details
Warfarin	Cytochrome P450 2C8 Cytochrome P450 2C18 Cytochrome P450 2C19	S-4'-Hydroxywarfarin	Details
Warfarin	Cytochrome P450 2C9 Cytochrome P450 2C18	R-4'-Hydroxywarfarin	Details
Warfarin	Cytochrome P450 2C19 Cytochrome P450 1A1 Cytochrome P450 1A2	R-6-Hydroxywarfarin	Details
Warfarin	Cytochrome P450 3A4	R-10-Hydroxywarfarin	Details
Warfarin	Cytochrome P450 1A1 Cytochrome P450 1A2 Cytochrome P450 2C19	R-8-Hydroxywarfarin	Details
Warfarin	Cytochrome P450 1A1 Cytochrome P450 1A2 Cytochrome P450 2C8	R-7-Hydroxywarfarin	Details
Warfarin		dehydrowarfarin	Details

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 t_1/2=37-89 hours; S-warfarin t_1/2=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	SMPDB ID
	Warfarin Pathway	SMP00268

理化性质

Properties

State

solid

Experimental Properties

Property	Value	Source
melting point	161 °C	PhysProp
water solubility	17 mg/L (at 20 °C)	TOMLIN,C (1997)
logP	2.70	HANSCH,C ET AL. (1995)
logS	-3.89	ADME Research, USCD
Caco2 permeability	-4.68	ADME Research, USCD
pKa	5.08	Not Available

Predicted Properties

Property	Value	Source
water solubility	4.72e-02 g/l	ALOGPS
logP	2.41	ALOGPS
logP	2.74	ChemAxon
logS	-3.8	ALOGPS
pKa (strongest acidic)	6.33	ChemAxon
pKa (strongest basic)	-6.6	ChemAxon
physiological charge	-1	ChemAxon
hydrogen acceptor count	3	ChemAxon
hydrogen donor count	1	ChemAxon
polar surface area	63.6	ChemAxon
rotatable bond count	4	ChemAxon
refractivity	86.86	ChemAxon
polarizability	31.98	ChemAxon

药物相互作用

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.
Capecitabine	Capecitabine 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. Subsequent cycles of 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. Increases serum 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.
Flurbiprofen	Flurbiprofen, 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.
Glutethimide	Glutethimide 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.
Homoharringtonine	Avoid 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.
Ibuprofen	Ibuprofen, 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.
Indomethacin	Indomethacin, 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.
Levothyroxine	Levothyroxine 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.
Liothyronine	Liothyronine 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.
Liotrix	Liotrix 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 acid	Mefenamic 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.
Metronidazole	Metronidazole 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.
Phenytoin	Warfarin 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.
Piroxicam	Piroxicam, 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.
Sitaxentan	Sitaxentan, 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 Wort	St. 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.
Triflusal	The 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.

食物相互作用

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.

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