indication

For decreasing blood clotting. Often used along with heparin for treatment of deep vein thrombosis.

pharmacology

Dicumarol is an coumarin-like compound found in sweet clover. It is used as an oral anticoagulant and acts by inhibiting the hepatic synthesis of vitamin K-dependent coagulation factors (prothrombin and factors VII, IX, and X). It is also used in biochemical experiments as an inhibitor of reductases.

mechanism of action

Dicumarol 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 decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.

toxicity

LD₅₀=233 mg/kg (orally in mice); LD₅₀=250 mg/kg (orally in rats)

drug interactions

Acetaminophen: Acetaminophen may increase the anticoagulant effect of dicumarol. Monitor for changes in the therapeutic and adverse effects of dicumarol if acetaminophen is initiated, discontinued or dose changed.

Acetohexamide: Dicumarol may increase the effect of sulfonylurea, acetohexamide.

Acetylsalicylic acid: Acetylsalicylic acid increases effect of the anticoagulant, dicumarol.

Allopurinol: Allopurinol may increase the anticoagulant effect of dicumarol.

Aminoglutethimide: Aminoglutethimide may decrease the anticoagulant effect of dicumarol.

Amiodarone: Amiodarone may increase the anticoagulant effect of dicumarol.

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

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

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

Azathioprine: Azathioprine may decrease the anticoagulant effect of dicumarol.

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

Betamethasone: The corticosteroid, betamethasone, alters the anticoagulant effect of dicumarol.

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

Capecitabine: Capecitabine may increase the anticoagulant effect of dicumarol by increasing its serum concentration.

Carbamazepine: Carbamazepine may decrease the anticoagulant effect of dicumarol by decreasing its serum concentration.

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

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

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

Celecoxib: Celecoxib may increase the anticoagulant effect of dicumarol.

Chlorpropamide: Dicumarol may increase the effect of sulfonylurea, chlorpropamide.

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

Cimetidine: Cimetidine may increase the anticoagulant effect of dicumarol.

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

Cisapride: Cisapride may increase the anticoagulant effect of dicumarol.

Citalopram: The SSRI, citalopram, increases the effect of anticoagulant, dicumarol.

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

Clofibrate: The fibrate increases the anticoagulant effect

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

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

Danazol: The androgen, danazol, may increase the anticoagulant effect of dicumarol.

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

Dexamethasone: The corticosteroid, dexamethasone, alters the anticoagulant effect of dicumarol.

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

Diclofenac: The NSAID, diclofenac, may increase the anticoagulant effect of dicumarol.

Dicloxacillin: Dicloxacillin may decrease the anticoagulant effect of dicumarol.

Diflunisal: The NSAID, diflunisal, may increase the anticoagulant effect of dicumarol.

Disulfiram: Disulfiram may increase the anticoagulant effect of dicumarol.

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

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

Ethchlorvynol: Ethchlorvynol may decrease the anticoagulant effect of dicumarol.

Ethinyl Estradiol: Increased thrombotic risk due to estrogen

Etodolac: The NSAID, etodolac, may increase the anticoagulant effect of dicumarol.

Etoricoxib: Etoricoxib may increase the anticoagulant effect of dicumarol.

Fenofibrate: Fenofibrate may increase the anticoagulant effect of dicumarol.

Fenoprofen: The NSAID, fenoprofen, may increase the anticoagulant effect of dicumarol.

Fluconazole: Fluconazole may increase the serum concentration of dicumarol by decreasing its metabolism.

Fludrocortisone: The corticosteroid, fludrocortisone, alters the anticoagulant effect of dicumarol.

Fluorouracil: The antineoplasic agent, fluorouracil, may increase the anticoagulant effect of dicumarol.

Fluoxetine: The SSRI, fluoxetine, increases the effect of anticoagulant, dicumarol.

Fluoxymesterone: The androgen, fluoxymesterone, may increase the anticoagulant effect of dicumarol.

Flurbiprofen: The NSAID, flurbiprofen, may increase the anticoagulant effect of dicumarol.

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

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

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

Fosphenytoin: Increased hydantoin levels and risk of bleeding

Gefitinib: Gefitinib may increase the anticoagulant effect of dicumarol.

Gemcitabine: Gemcitabine may increase the anticoagulant effect of dicumarol.

Gemfibrozil: Gemfibrozil may increase the anticoagulant effect of dicumarol.

Gliclazide: Dicumarol may increase the effect of sulfonylurea, gliclazide.

Glutethimide: Glutethimide may decrease the anticoagulant effect of dicumarol.

Glyburide: Dicumarol may increase the effect of sulfonylurea, glibenclamide.

Griseofulvin: Griseofulvin may decrease the anticoagulant effect of dicumarol.

Hydrocortisone: The corticosteroid, hydrocortisone, alters the anticoagulant effect of dicumarol.

Ibuprofen: The NSAID, ibuprofen, may increase the anticoagulant effect of dicumarol.

Imatinib: Imatinib may increase the anticoagulant effect of dicumarol.

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

Indomethacin: The NSAID, indomethacin, may increase the anticoagulant effect of dicumarol.

Isoniazid: Isoniazid may increase the anticoagulant effect of dicumarol.

Itraconazole: Itraconazole may increase the anticoagulant effect of dicumarol.

Ketoconazole: Ketoconazole may increase the anticoagulant effect of dicumarol.

Ketoprofen: The NSAID, ketoprofen, may increase the anticoagulant effect of dicumarol.

Ketorolac: The NSAID, ketorolac, may increase the anticoagulant effect of dicumarol.

Leflunomide: Leflunomide may increase the anticoagulant effect of dicumarol.

Levamisole: Levamisole may increase the anticoagulant effect of dicumarol.

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

Levothyroxine: The thyroid hormone, levothyroxine, increase the anticoagulant effect of dicumarol.

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

Lumiracoxib: Lumiracoxib may increase the anticoagulant effect of dicumarol.

Medroxyprogesterone: Medroxyprogesterone may increase the anticoagulant effect of dicumarol.

Mefenamic acid: The NSAID, mefanamic acid, may increase the anticoagulant effect of dicumarol.

Mefloquine: Mefloquine may increase the anticoagulant effect of dicumarol.

Meloxicam: Meloxicam may increase the anticoagulant effect of dicumarol.

Mercaptopurine: Mercaptopurine may decrease the anticoagulant effect of dicumarol.

Methimazole: The antithyroid agent, methimazole, may decrease the anticoagulant effect of dicumarol.

Metronidazole: Metronidazole may increase the anticoagulant effect of dicumarol.

Miconazole: Miconazole may increase the serum concentration of dicumarol by decreasing its metabolism.

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

Mitotane: Mitotane may decrease the anticoagulant effect of dicumarol.

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

Nabumetone: The NSAID, nabumetone, may increase the anticoagulant effect of dicumarol.

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

Naproxen: The NSAID, naproxen, may increase the anticoagulant effect of dicumarol.

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

Nevirapine: Nevirapine may decrease the anticoagulant effect of dicumarol.

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

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

Orlistat: Orlistat may increase the anticoagulant effect of dicumarol.

Oxaprozin: The NSAID, oxaprozin, may increase the anticoagulant effect of dicumarol.

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

Paroxetine: The SSRI, paroxetine, increases the effect of anticoagulant, dicumarol.

Pentoxifylline: Pentoxifylline may increase the anticoagulant effect of dicumarol.

Phenobarbital: The barbiturate, phenobarbital, decreases the anticoagulant effect, dicumarol.

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

Phenytoin: Increased hydantoin levels and risk of bleeding

Piroxicam: The NSAID, piroxicam, may increase the anticoagulant effect of dicumarol.

Prednisolone: The corticosteroid, prednisolone, alters the anticoagulant effect of dicumarol.

Prednisone: The corticosteroid, prednisone, alters the anticoagulant effect of dicumarol.

Primidone: The barbiturate, primidone, decreases the anticoagulant effect, dicumarol.

Propafenone: Propafenone may increase the anticoagulant effect of dicumarol.

Propoxyphene: Propoxyphene may increase the anticoagulant effect of dicumarol.

Propylthiouracil: The anti-thyroid agent, propylthiouracil, may decrease the anticoagulant effect of dicumarol.

Quinidine: Quinidine may increase the anticoagulant effect of dicumarol.

Quinine: Quinine may increase the anticoagulant effect of dicumarol.

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

Rifabutin: Rifabutin may decrease the anticoagulant effect of dicumarol.

Rifampin: Rifampin may decrease the anticoagulant effect of dicumarol.

Telithromycin: Telithromycin may increase the anticoagulant effect of dicumarol.

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

Testosterone: The androgen may increase the anticoagulant effect of dicumarol.

Tetracycline: Tetracycline may increase the anticoagulant effect of dicumarol.

Tigecycline: Tigecycline may increase the anticoagulant effect of dicumarol.

Triamcinolone: The corticosteroid, triamcinolone, alters the anticoagulant effect of dicumarol.