Trade Names:Coumadin- Tablets 1 mg- Tablets 2 mg- Tablets 2.5 mg- Tablets 3 mg- Tablets 4 mg- Tablets 5 mg- Tablets 6 mg- Tablets 7.5 mg- Tablets 10 mg- Powder for Injection, lyophilized 2 mg/mL
Trade Names:Jantoven- Tablets 1 mg- Tablets 2 mg- Tablets 2.5 mg- Tablets 3 mg- Tablets 4 mg- Tablets 5 mg- Tablets 6 mg- Tablets 7.5 mg- Tablets 10 mgApo-Warfarin (Canada)Gen-Warfarin (Canada)Taro-Warfarin (Canada)
Interferes with hepatic synthesis of vitamin K–dependent clotting factors, resulting in in-vivo depletion of clotting factors II, VII, IX, and X, and proteins C and S.
It is completely absorbed. T max is 4 h.
Vd is about 0.14 L/kg. It is about 99% bound to plasma protein.
The elimination of warfarin is almost entirely by metabolism. It is metabolized by CYP-450 to inactive hydroxylated metabolites (predominant route) and by reductases to reduced metabolites (warfarin alcohols).
Metabolites are principally excreted into urine and to a lesser extent into the bile. The t ½ after a single dose is about 1 wk; however, the effective t ½ ranges from 20 to 60 h. The Cl of R-warfarin is 50% that of S-warfarin. The t ½ of R-warfarin is about 37 to 89 h and S-warfarin about is 21 to 43 h. About 92% of orally administered doses are recovered in urine.
No dosage adjustment is needed.Hepatic Function Impairment
Hepatic function impairment can potentiate the response to warfarin through impaired synthesis of clotting factors and decreased metabolism of warfarin.Elderly
Patients 60 yr of age and older appear to exhibit greater than expected PT/INR response to warfarin. As a patient's age increases, a lower dose is usually required to produce a therapeutic level of anticoagulation.Race
Asian patients may require lower initiation and maintenance doses.Pharmacogenetics
About 55% of the variability in warfarin dose can be explained by polymorphisms in the vitamin K epoxide reductase (VKORC1) and CYP2C9 genotypes.
Prophylaxis and treatment of pulmonary embolism, and venous thrombosis and its extension; prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation and cardiac valve replacement; reduction of risk of death, recurrent MI, and thromboembolic events such as stroke or systemic embolism after MI.
Pregnancy; hemorrhagic tendencies or blood dyscrasias; recent or contemplated surgery of the CNS, eye, or traumatic surgery resulting in large open surfaces; bleeding tendencies associated with active ulceration or overt bleeding of GI, GU, or respiratory tracts; cerebrovascular hemorrhage; cerebral or dissecting aorta aneurysms; pericarditis and pericardial effusions; bacterial endocarditis; threatened abortion, eclampsia, and preeclampsia; spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrolled bleeding; major regional, lumbar block anesthesia; malignant hypertension; inadequate laboratory facilities; unsupervised patients with senility; hypersensitivity to any component of the product.
PO 2 to 5 mg/day initially; adjust daily dose according to PT or INR determinations. Usual maintenance dose is 2 to 10 mg/day. Lower dosages are recommended in patients with genetic variations in CYP2C9 and VKORC1 enzymes as well as in elderly and/or debilitated patients.Adults
IV Provides an alternative administration route for patients who cannot receive oral drugs. The IV dosages would be the same as those that would be used orally. Administer as a slow bolus injection over 1 to 2 min in a peripheral vein.
Store at 59° to 86°F. Protect from light. After reconstitution, store IV solution at 59° to 86°F and use within 4 h. Do not refrigerate.
Decreased anticoagulant effect of warfarin.Acetaminophen, amiodarone, androgens, azithromycin, azole antifungal agents, capecitabine, carboplatin, cefamandole, cefazolin, cefoperazone, cefotetan, cefoxitin, ceftriaxone, chloramphenicol, cimetidine, ciprofloxacin, clarithromycin, cranberry juice, cyclophosphamide, danshen, dextrothyroxine, disulfiram, dong quai, doxycycline, erythromycin, etoposide, fenofibrate, fluorouracil, gefitinib, gemcitabine, gemfibrozil, ginkgo biloba, ginseng, glucagon, HMG-Co reductase inhibitors, levamisole, levofloxacin, methimazole, metronidazole, miconazole, moxifloxacin, nalidixic acid, norfloxacin, NSAIDs, ofloxacin, paclitaxel, phenylbutazone, propylthiouracil, quinidine, quinine, salicylates, sulfinpyrazone, sulfonamides, telithromycin, thyroid hormones, ticarcillin, tramadol, tricyclic antidepressants, and vitamin E
Increased anticoagulant effect of warfarin.Hydantoins
Serum hydantoin concentration may be elevated, increasing risk of toxicity.
Oral anticoagulants may cause red-orange discoloration of alkaline urine, interfering with some laboratory tests.
Angina syndrome; hypotension; syncope; vasculitis.
Asthenia; dizziness; fatigue; headache; lethargy; loss of consciousness; malaise; paresthesia (including feeling cold and chills).
Alopecia; dermatitis (including bullous eruptions); necrosis of skin; pallor; pruritus; rash; urticaria.
Abdominal pain (including cramping); bloating; diarrhea; flatulence; nausea; taste perversion; vomiting.
Anemia; bleeding; hemorrhagic complication (including difficulty breathing or swallowing; dizziness; headache; hypotension; pain in the abdomen, chest, joint, or muscle; paralysis; paresthesia; shortness of breath; unexplained shock; unexplained swelling; weakness).
Cholestatic hepatic injury; elevated liver enzymes; hepatitis; jaundice.
Allergic/hypersensitivity reactions (including anaphylactic reactions); chest pain; cold intolerance; coma; edema; fever; purple toe syndrome; systemic cholesterol microembolism; pain.
Major or fatal bleeding can occur. Risk factors include INR greater than 4, 65 yr of age and older, highly variable INRs, history of GI bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, malignancy, trauma, renal function impairment, concomitant drugs (see Interactions), and long duration of warfarin therapy.
Regularly monitor INR in all patients. Individualize treatment based on PT or INR.
Category X .
Safety and efficacy not established in children younger than 18 yr of age.
May be more sensitive to effects.
Reactions range from mild to life-threatening. Symptoms may be dermatologic (eg, erythema, eczematous rash, exfoliative dermatitis, exudative erythema multiforme, alopecia), hematologic (eg, eosinophilia, leukopenia, thrombocytopenia), renal (eg, nephropathy, nephritis, oliguria), GI (eg, enanthema, severe stomatitis), or hepatic (eg, mixed hepatocellular damage, cholestasis, jaundice). If signs or symptoms occur, discontinue therapy.
There is increased risk associated with using warfarin in patients with trauma, infection, renal function impairment, dietary insufficiency, uncontrolled hypertension, polycythemia vera, vasculitis, indwelling catheters. Evaluate benefits of therapy vs risks.
Discontinue therapy if patient develops signs and symptoms of adrenal insufficiency.
Hereditary, familial, or clinical protein C deficiency has been associated with necrosis following warfarin therapy. If warfarin is the suspected cause of necrosis, discontinue administration.
Systemic cholesterol microembolization from release of atheromatous plaque emboli. Discontinue therapy.
Adjust dose to maintain PT or INR at low end of therapeutic range for patients who must be anticoagulated during dental or surgical procedures.
Hematuria, excessive menstrual bleeding, melena, oozing from superficial injuries, petechiae.
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