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Warfarin sodium
Warfarin sodium (Coumadin)
Warfarin sodium
(WAR-far-in)
Pregnancy Category: X Coumadin Warfilone (Rx)

Classification: Anticoagulant

Action/Kinetics: Interferes with synthesis of vitamin K-dependent clotting factors resulting in depletion of clotting factors II, VII, IX, and X. Has no direct effect on an established thrombus although therapy may prevent further extension of a formed clot as well as secondary thromboembolic problems. Well absorbed from the GI tract although food affects the rate (but not the extent) of absorption. Suitable for parenteral administration. Peak activity: 1.5-3 days; duration: 2-5 days. t1/2: 1-2.5 days. Highly bound to plasma proteins. Metabolized in the liver and inactive metabolites are excreted through the urine and feces.

Uses: Prophylaxis and treatment of venous thrombosis and its extension. Prophylaxis and treatment of atrial fibrillation with embolization. Prophylaxis and treatment of pulmonary embolism. Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation. Investigational: Adjunct to treat small cell carcinoma of the lung with chemotherapy and radiation. Prophylaxis of recurrent transient ischemic attacks and to reduce the risk of recurrent MI. In combination with aspirin to reduce risk of a second MI.

Contraindications: Lactation. IM use. Use of a large loading dose (30 mg) is not recommended due to increased risk of hemorrhage and lack of more rapid protection.

Special Concerns: Geriatric clients may be more sensitive. Anticoagulant use in the following clients leads to increased risk: trauma, infection, renal insufficiency, sprue, vitamin K deficiency, severe to moderate hypertension, polycythemia vera, severe allergic disorders, vasculitis, indwelling catheters, severe diabetes, anaphylactic disorders, surgery or trauma resulting in large exposed raw surfaces. Use with caution in impaired hepatic and renal function. Safety and efficacy have not been determined in children less than 18 years of age. Careful monitoring and dosage regulation are required during dentistry and surgery.

Side Effects: CV: Hemorrhage is the main side effect and may occur from any tissue or organ. Symptoms of hemorrhage include headache, paralysis; pain in the joints, abdomen, or chest; difficulty in breathing or swallowing; SOB, unexplained swelling or shock. GI: N&V;, diarrhea, sore mouth, mouth ulcers, anorexia, abdominal cramping, paralytic ileus, intestinal obstruction (due to intramural or submucosal hemorrhage). Hepatic: Hepatotoxicity, cholestatic jaundice. Dermatologic: Dermatitis, exfoliative dermatitis, urticaria, alopecia, necrosis or gangrene of the skin and other tissues (due to protein C deficiency). Miscellaneous: Pyrexia, red-orange urine, priapism, leukopenia, systemic cholesterol microembolization (``purple toes'' syndrome), hypersensitivity reactions, compressive neuropathy secondary to hemorrhage adjacent to a nerve (rare).

Laboratory Test Alterations: False levels of serum theophylline determined by Schack and Waxler UV method (warfarin and dicumarol). Metabolites of indanedione derivatives may color alkaline urine red; color disappears upon acidification.

Overdose Management: Symptoms: Early symptoms include melena, petechiae, microscopic hematuria, oozing from superficial injuries (e.g., nicks from shaving, excessive bruising, bleeding from gums after teeth brushing), excessive menstrual bleeding. Treatment: Discontinue therapy. Administer oral or parenteral phytonadione (e.g., 2.5-10 mg PO or 5-25 mg parenterally). In emergency situations, 200-250 mL fresh frozen plasma or commercial factor IX complex. Fresh whole blood may be needed in clients unresponsive to phytonadione.

Drug Interactions: Warfarin is responsible for more adverse drug interactions than any other group. Clients on anticoagulant therapy must be monitored carefully each time a drug is added or withdrawn. Monitoring usually involves determination of PT or INR. In general, a lengthened PT or INR means potentiation of the anticoagulant. Since potentiation may mean hemorrhages, a lengthened PT or INR warrants reduction of the dosage of the anticoagulant.However, the anticoagulant dosage must again be increased when the second drug is discontinued. A shortened PT or INR means inhibition of the anticoagulant and may require an increase in dosage. Acetaminophen / Anticoagulant effect Alcohol, ethyl / Chronic use warfarin effect Aminoglutethimide / Warfarin effect R/T liver breakdown Aminoglycoside antibiotics / Warfarin effect R/T interference with vitamin K Amiodarone / Warfarin effect R/T liver breakdown Androgens / Warfarin effect Ascorbic acid / Warfarin effect by unknown mechanism Barbiturates / Warfarin effect R/T liver breakdown Beta-adrenergic blockers / Warfarin effect Bromelain / Tendency for bleeding Capecitabine / Risk of bleeding and altered coagulation Carbamazepine / Warfarin effect R/T liver breakdown Celecoxib / PT Cephalosporins / Warfarin effect R/T effects on platelet function Chloral hydrate / Warfarin effect R/T plasma protein binding Chloramphenicol / Warfarin effect R/T liver breakdown Cholestyramine / Anticoagulant effect R/T binding and absorption from GI tract Cimetidine / Anticoagulant effect R/T liver breakdown Cinchona bark / Anticoagulant effect Clarithromycin / Warfarin effect R/T liver metabolism Clofibrate / Anticoagulant effect Contraceptives, oral / Anticoagulant effect R/T activity of certain clotting factors (VII and X); rarely, the opposite effect of risk of thromboembolism Contrast media containing iodine / Warfarin effect by PT Corticosteroids / Warfarin effect; also risk of GI bleeding R/T steroids ulcerogenic effect Cyclophosphamide / Anticoagulant effect Dextrothyroxine / Warfarin effect Dicloxacillin / Warfarin effect Diflunisal / Anticoagulant effect and risk of bleeding R/T effect on platelet function and GI irritation Disulfiram / Warfarin effect Dong quai / Potential for anticoagulant effects Erythromycin / Warfarin effect R/T liver metabolism Estrogens / Anticoagulant response by activity of certain clotting factors; rarely, the opposite effect of risk of thromboembolism Etretinate / Warfarin effect R/T liver breakdown Evening primrose oil / Potential to platelet aggregation Feverfew / Potential to platelet aggregation Fluconazole / Warfarin effect Garlic / Potential to platelet aggregation Gemfibrozil / Warfarin effect Ginger / Potential to platelet aggregation Ginkgo biloba / Potential to platelet aggregation Ginseng, panax / Potential to platelet aggregation Glucagon / Warfarin effect Glutethimide / Warfarin effect R/T liver breakdown Grapeseed extract / Potential to platelet aggregation Griseofulvin / Warfarin effect Hydantoins / Warfarin effect; also, hydantoin serum levels Hypoglycemics, oral / Warfarin effect R/T plasma protein binding; also, effect of sulfonylureas Ifosfamide / Warfarin effect R/T liver breakdown and displacement from protein binding sites Indomethacin / Warfarin effect R/T effect on platelet function; also, indomethacin is ulcerogenic GI hemorrhage Isoniazid / Warfarin effect Ketoconazole / Warfarin effect Loop diuretics / Warfarin effect by displacement from protein binding sites Lovastatin / Warfarin effect R/T liver breakdown Metronidazole / Warfarin effect R/T liver breakdown Miconazole / Warfarin effect Mineral oil / Hypoprothrombinemia by absorption of vitamin K from GI tract; also mineral oil may absorption of warfarin from GI tract Moricizine / Warfarin effect Nafcillin / Warfarin effect Nalidixic acid / Warfarin effect R/T displacement from protein binding sites Nonsteroidal anti-inflammatory agents / Warfarin effect; risk of bleeding R/T effects on platelet function and GI irritation Omeprazole / Warfarin effect R/T liver breakdown Penicillins / Warfarin effect &arrowrt; risk of bleeding R/T effects on platelet function Propafenone / Warfarin effect R/T liver breakdown Propoxyphene / Warfarin effect Quinidine, quinine / Warfarin effect R/T liver breakdown Quinolones / Warfarin effect Rifampin / Anticoagulant effect R/T liver breakdown Ritonavir / Possible anticoagulant effect St. John's wort / Possible warfarin plasma levels R/T metabolism Salicylates / Warfarin effect and risk of bleeding R/T effect on platelet function and GI irritation Spironolactone / Warfarin effect R/T hemoconcentration of clotting factors due to diuresis Streptokinase / Warfarin effect Sucralfate / Warfarin effect Sulfamethoxazole and Trimethoprim / Warfarin effect R/T liver breakdown Sulfinpyrazone / Anticoagulant effect R/T liver breakdown and inhibition of platelet aggregation Sulfonamides / Sulfonamide effects Sulindac / Warfarin effect Tamoxifen / Warfarin effect Tetracyclines / Warfarin effect R/T interference with vitamin K Thiazide diuretics / Warfarin effect R/T hemoconcentration of clotting factors due to diuresis Thioamines / Warfarin effect Thiopurines / Warfarin effect R/T synthesis or activation of prothrombin Thyroid hormones / Anticoagulant effect Trazodone / Warfarin effect Troglitazone / Possible warfarin effect R/T liver breakdown or displacement from plasma proteins Urokinase / Warfarin effect Vitamin E / Warfarin effect R/T interference with vitamin K Vitamin K / Warfarin effect

How Supplied: Powder for injection: 5 mg; Tablet: 1 mg, 2 mg, 2.5 mg, 4 mg, 5 mg, 6 mg, 7.5 mg, 10 mg

Dosage
•Tablets, IV Induction.
Adults, initial: 5-10 mg/day for 2-4 days; then, adjust dose based on prothrombin or INR determinations. A lower dose should be used in geriatric or debilitated clients or clients with increased sensitivity. Dosage has not been established for children.
Maintenance.
Adults: 2-10 mg/day, based on prothrombin or INR.
Prevent blood clots with prosthetic heart valve replacement.
2-5 mg daily.