indication

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

pharmacology

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.

toxicity

LD₅₀=374 (orally in mice)

biotransformation

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.

absorption

Rapidly absorbed following oral administration with considerable interindividual variations. Also absorbed percutaneously.

half life

R-warfarin t_1/2=37-89 hours; S-warfarin t_1/2=21-43 hours.

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.

drug interactions

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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