COUMADIN Warfarin Sodium 2.5mg Tablet 1's
RXDRUG-DR-3744-1pc
Discreet Packaging
FDA-registered Products
FDA-licensed Pharmacies
Indications/Uses
Prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, thromboembolic complications associated with atrial fibrillation, cardiac valve replacement and as an adjunct in the prophylaxis of systemic embolism after myocardial infarction.
Dosage/Direction for Use
Administration: Must be individualized for each patient according to the particular patient's sensitivity to the drug. The dosage should be adjusted based upon the results of the 1-stage prothrombin time (PT). Different thromboplastin reagents vary substantially in their responsiveness to sodium warfarin-induced effects on PT. To define the appropriate therapeutic regimen, it is important to be familiar with the sensitivity of the thromboplastin reagent used in the laboratory and its relationship to the International Reference Preparation (IRP), a sensitive thromboplastin reagent prepared from human brain.
Early clinical studies of oral anticoagulants, which formed the basis for recommended therapeutic ranges of 1.5-2.5 times control PT, used sensitive human brain thromboplastin. When using the less sensitive rabbit brain thromboplastins commonly employed in PT assays today, adjustments must be made to the targeted PT range that reflect this decrease in sensitivity.
Available clinical evidence indicates that an INR of 2-3 (eg, PT ratio of 1.2-1.5) when measuring with the less sensitive thromboplastin reagents, ISI=2.8 (see table) is sufficient for prophylaxis and treatment of venous thromboembolism and minimizes the risk of hemorrhage associated with higher INRs. Five (5) recent clinical trials evaluated the effects of warfarin in patients with non-valvular atrial fibrillation (AF). Meta-analysis findings of these studies revealed that the effects of warfarin in reducing thromboembolic events including stroke were similar at either moderately high INR (2-4.5) or low INR (1.4-3). There was a significant reduction in minor bleeds at the low INR. Similar data from clinical studies in valvular atrial fibrillation patients are not available. The trials in non-valvular atrial fibrillation support the American College of Chest Physicians (ACCP) recommendation that an INR of 2-3 be used for long-term warfarin therapy in appropriate AF patients. In cases where the risk of thromboembolism is great eg, in patients with recurrent systemic embolism, a higher INR may be required. A PT ratio of >2 appears to provide no additional therapeutic benefit in most patients and is associated with a higher risk of bleeding.
In patients with mechanical heart valve(s), long-term prophylaxis with warfarin to an INR of 2.5-3.5 is recommended. In patients with bioprosthetic heart valve(s), based on limited data, the American College of Chest Physicians recommends warfarin therapy to an INR of 2-3 for 12 weeks after valve insertion. In patients with additional risk factors eg, atrial fibrillation or prior thromboembolism, consideration should be given for longer term therapy.
The proceedings and recommendations of the 1986 National Conference on Antithrombotic Therapy review and evaluate issues related to oral anticoagulant therapy and the sensitivity of thromboplastin reagents and provide additional guidelines for defining the appropriate therapeutic regimen.
The conversion of the INR to PT ratios for the less-intense (INR 2-3) and more intense (INR 2.5-3.5) therapeutic range recommended by the ACCP for thromboplastins over a range of ISI values is shown in the table. (See table.)
Early clinical studies of oral anticoagulants, which formed the basis for recommended therapeutic ranges of 1.5-2.5 times control PT, used sensitive human brain thromboplastin. When using the less sensitive rabbit brain thromboplastins commonly employed in PT assays today, adjustments must be made to the targeted PT range that reflect this decrease in sensitivity.
Available clinical evidence indicates that an INR of 2-3 (eg, PT ratio of 1.2-1.5) when measuring with the less sensitive thromboplastin reagents, ISI=2.8 (see table) is sufficient for prophylaxis and treatment of venous thromboembolism and minimizes the risk of hemorrhage associated with higher INRs. Five (5) recent clinical trials evaluated the effects of warfarin in patients with non-valvular atrial fibrillation (AF). Meta-analysis findings of these studies revealed that the effects of warfarin in reducing thromboembolic events including stroke were similar at either moderately high INR (2-4.5) or low INR (1.4-3). There was a significant reduction in minor bleeds at the low INR. Similar data from clinical studies in valvular atrial fibrillation patients are not available. The trials in non-valvular atrial fibrillation support the American College of Chest Physicians (ACCP) recommendation that an INR of 2-3 be used for long-term warfarin therapy in appropriate AF patients. In cases where the risk of thromboembolism is great eg, in patients with recurrent systemic embolism, a higher INR may be required. A PT ratio of >2 appears to provide no additional therapeutic benefit in most patients and is associated with a higher risk of bleeding.
In patients with mechanical heart valve(s), long-term prophylaxis with warfarin to an INR of 2.5-3.5 is recommended. In patients with bioprosthetic heart valve(s), based on limited data, the American College of Chest Physicians recommends warfarin therapy to an INR of 2-3 for 12 weeks after valve insertion. In patients with additional risk factors eg, atrial fibrillation or prior thromboembolism, consideration should be given for longer term therapy.
The proceedings and recommendations of the 1986 National Conference on Antithrombotic Therapy review and evaluate issues related to oral anticoagulant therapy and the sensitivity of thromboplastin reagents and provide additional guidelines for defining the appropriate therapeutic regimen.
The conversion of the INR to PT ratios for the less-intense (INR 2-3) and more intense (INR 2.5-3.5) therapeutic range recommended by the ACCP for thromboplastins over a range of ISI values is shown in the table. (See table.)
Initial Dosage: The dosing of Coumadin must be individualized according to patient's sensitivity to the drug as indicated by the INR and/or PT ratio.
Use of a large loading dose may increase the incidence of hemorrhage and other complications, does not offer more rapid protection against thrombi formation, and is not recommended. Low initiation doses are recommended for elderly and/or debilitated patients and patients with increased sensitivity to Coumadin (see Precautions).
It is recommended that Coumadin therapy be initiated with a dose of 2-5 mg/day with dosage adjustments based on the results of INR and/or PT ratio determinations.
Maintenance: Most patients are satisfactorily maintained at a dose of 2-10 mg daily. Flexibility of dosage is provided by breaking scored-tablets in half. The individual dose and interval should be gauged by the patient's prothrombin response.
Duration of Therapy: The duration of therapy in each patient should be individualized. In general, anticoagulant therapy should be continued until the danger of thrombosis and embolism has passed.
Laboratory Control: The PT reflects the depression of vitamin K-dependent Factors VII, IX, X and II. There are several modifications of the 1-stage PT and the physician should become familiar with the specific method used in his laboratory. The degree of anticoagulation indicated by any range of PTs may be altered by the type of thromboplastin used; the appropriate therapeutic range must be based on the experience of each laboratory. The PT should be determined daily after the administration of the initial dose until PT results stabilize in the therapeutic range. Intervals between subsequent PT determinations should be based upon the physicians' judgment of the patient's reliability and response to Coumadin in order to maintain the individual within the therapeutic range. Acceptable intervals for PT determinations are normally within the range of 1-4 weeks after a stable dosage has been determined. To ensure adequate control, it is recommended that additional PT tests are done when other warfarin products are interchanged with Coumadin and also if other medications are co-administered with it (see Precautions).
Treatment During Dentistry and Surgery: The management of patients who undergo dental and surgical procedures requires close liaison between attending physicians, surgeons and dentists. In patients who must be anticoagulated prior to, during or immediately following dental or surgical procedures, adjusting the dosage of Coumadin to maintain the PT at the low end of the therapeutic range, may safely allow for continued anticoagulation. The operative site should be sufficiently limited and accessible to permit the effective use of local procedures for hemostasis. Under these conditions, dental and surgical procedures may be performed without undue risk of hemorrhage.
Conversion from Heparin Therapy: Since the onset of the Coumadin effect is delayed, heparin is preferred initially for rapid anticoagulation. Conversion to Coumadin may begin concomitantly with heparin therapy or may be delayed 3-6 days. As heparin may affect the PT, patients receiving both heparin and Coumadin should have blood for PT determination, drawn at least: 5 hrs after the last IV bolus dose of heparin; or 4 hrs after cessation of a continuous IV infusion of heparin; or 24 hrs after the last SC heparin injection.
When Coumadin has produced the desired therapeutic range or prothrombin activity, heparin may be discontinued.
Overdosage
Symptoms: Suspected or overt abnormal bleeding (ie, appearance of blood in stools or urine, hematuria, excessive menstrual bleeding, melena, petechiae, excessive bruising or persistent oozing from superficial injuries) are early manifestations of anticoagulation beyond a safe and satisfactory level.
Treatment: Excessive anticoagulation, with or without bleeding, may be controlled by discontinuing Coumadin therapy and if necessary, by administration of oral or parenteral vitamin K1. (See recommendations accompanying vitamin K1 preparations prior to use.)
Such use of vitamin K1 reduces response to subsequent Coumadin therapy. Patients may return to a pre-treatment thrombotic status following the rapid reversal of a prolonged PT. Resumption of Coumadin administration reverses the effect of vitamin K1 and a therapeutic PT can again be obtained by careful dosage adjustment. If rapid anticoagulation is indicated, heparin may be preferable for initial therapy.
If minor bleeding progresses to major bleeding, give 5-25 mg (rarely up to 50 mg) parenteral vitamin K1. In emergency situations of severe hemorrhage, clotting factors can be returned to normal by administering 200-500 mL of fresh whole blood or fresh frozen plasma, or by giving commercial Factor IX complex. A risk of hepatitis and other viral diseases is associated with the use of these blood products; Factor IX complex is also associated with an increased risk of thrombosis. Therefore, these preparations should be used only in exceptional or life-threatening bleeding episodes secondary to Coumadin overdosage.
Purified Factor IX preparations should not be used because they cannot increase the levels of prothrombin, Factor VII and Factor X which are also depressed along with the levels of Factor IX as a result of Coumadin treatment.
Packed red blood cells may also be given if significant blood loss has occurred. Infusions of blood or plasma should be monitored carefully to avoid precipitating pulmonary edema in elderly patients or patients with heart disease.
Treatment: Excessive anticoagulation, with or without bleeding, may be controlled by discontinuing Coumadin therapy and if necessary, by administration of oral or parenteral vitamin K1. (See recommendations accompanying vitamin K1 preparations prior to use.)
Such use of vitamin K1 reduces response to subsequent Coumadin therapy. Patients may return to a pre-treatment thrombotic status following the rapid reversal of a prolonged PT. Resumption of Coumadin administration reverses the effect of vitamin K1 and a therapeutic PT can again be obtained by careful dosage adjustment. If rapid anticoagulation is indicated, heparin may be preferable for initial therapy.
If minor bleeding progresses to major bleeding, give 5-25 mg (rarely up to 50 mg) parenteral vitamin K1. In emergency situations of severe hemorrhage, clotting factors can be returned to normal by administering 200-500 mL of fresh whole blood or fresh frozen plasma, or by giving commercial Factor IX complex. A risk of hepatitis and other viral diseases is associated with the use of these blood products; Factor IX complex is also associated with an increased risk of thrombosis. Therefore, these preparations should be used only in exceptional or life-threatening bleeding episodes secondary to Coumadin overdosage.
Purified Factor IX preparations should not be used because they cannot increase the levels of prothrombin, Factor VII and Factor X which are also depressed along with the levels of Factor IX as a result of Coumadin treatment.
Packed red blood cells may also be given if significant blood loss has occurred. Infusions of blood or plasma should be monitored carefully to avoid precipitating pulmonary edema in elderly patients or patients with heart disease.
Administration
May be taken with or without food.
Contraindications
Anticoagulation is contraindicated in any localized or general physical condition or personal circumstance in which the hazard of hemorrhage might be greater than its potential clinical benefits eg, pregnancy. Pregnancy: Women who are or may become pregnant because the drug passes through the placental barrier and may cause fatal hemorrhage to the fetus in utero. Furthermore, there have been reports of birth malformations in children born to mothers who have been treated with warfarin during pregnancy.
Embryopathy characterized by nasal hypoplasia with or without stippled epiphyses (chondrodysplasia punctata) has been reported in pregnant women exposed to warfarin during the 1st trimester. Central nervous system abnormalities also have been reported, including dorsal midline dysplasia characterized by agenesis of the corpus callosum, Dandy-Walker malformation, and midline cerebellar atrophy. Ventral midline dysplasia, characterized by optic atrophy and eye abnormalities has been observed. Mental retardation, blindness, and other central nervous system abnormalities have been reported in association with 2nd and 3rd trimester exposure. Although rare, teratogenic reports following in utero exposure to warfarin include urinary tract anomalies eg, single kidney, asplenia, anencephaly, spina bifida, cranial nerve palsy, hydrocephalus, cardiac defects and congenital heart disease, polydactyly, deformities of toes, diaphragmatic hernia, and corneal leukoma.
Spontaneous abortion and stillbirth are known to occur and a higher risk of fetal mortality is associated with the use of warfarin.
Women of childbearing potential who are candidates for anticoagulant therapy should be carefully evaluated and the indications critically reviewed with the patient. If the patient becomes pregnant while taking this drug, she should be apprised of the potential risks to the fetus, and the possibility of termination of the pregnancy should be discussed in light of those risks.
Hemorrhagic tendencies or blood dyscrasias.
Recent or contemplated surgery of the central nervous system, eye, or traumatic surgery resulting in large open surfaces.
Bleeding tendencies associated with active ulceration or overt bleeding of the gastrointestinal, genitourinary or respiratory tracts; cerebrovascular hemorrhage; aneurysms-cerebral, dissecting aorta; pericarditis, pericardial effusions and bacterial endocarditis.
Threatened abortion, eclampsia and preeclampsia.
Inadequate laboratory facilities or unsupervised senility, alcoholism, psychosis or lack of patient cooperation.
Spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding.
Miscellaneous: Major regional, lumbar block anesthesia and malignant hypertension.
Embryopathy characterized by nasal hypoplasia with or without stippled epiphyses (chondrodysplasia punctata) has been reported in pregnant women exposed to warfarin during the 1st trimester. Central nervous system abnormalities also have been reported, including dorsal midline dysplasia characterized by agenesis of the corpus callosum, Dandy-Walker malformation, and midline cerebellar atrophy. Ventral midline dysplasia, characterized by optic atrophy and eye abnormalities has been observed. Mental retardation, blindness, and other central nervous system abnormalities have been reported in association with 2nd and 3rd trimester exposure. Although rare, teratogenic reports following in utero exposure to warfarin include urinary tract anomalies eg, single kidney, asplenia, anencephaly, spina bifida, cranial nerve palsy, hydrocephalus, cardiac defects and congenital heart disease, polydactyly, deformities of toes, diaphragmatic hernia, and corneal leukoma.
Spontaneous abortion and stillbirth are known to occur and a higher risk of fetal mortality is associated with the use of warfarin.
Women of childbearing potential who are candidates for anticoagulant therapy should be carefully evaluated and the indications critically reviewed with the patient. If the patient becomes pregnant while taking this drug, she should be apprised of the potential risks to the fetus, and the possibility of termination of the pregnancy should be discussed in light of those risks.
Hemorrhagic tendencies or blood dyscrasias.
Recent or contemplated surgery of the central nervous system, eye, or traumatic surgery resulting in large open surfaces.
Bleeding tendencies associated with active ulceration or overt bleeding of the gastrointestinal, genitourinary or respiratory tracts; cerebrovascular hemorrhage; aneurysms-cerebral, dissecting aorta; pericarditis, pericardial effusions and bacterial endocarditis.
Threatened abortion, eclampsia and preeclampsia.
Inadequate laboratory facilities or unsupervised senility, alcoholism, psychosis or lack of patient cooperation.
Spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding.
Miscellaneous: Major regional, lumbar block anesthesia and malignant hypertension.
Warnings
The most serious risks associated with anticoagulant therapy with warfarin sodium are hemorrhage in any tissue or organ and, less frequently, necrosis and/or gangrene of skin and other tissues. The risk of hemorrhage is related to the level of intensity and the duration of anticoagulant therapy. Hemorrhage and necrosis have, in some cases, been reported to result in death or permanent disability. Necrosis appears to be associated with local thrombosis and usually appears within a few days of the start of anticoagulant therapy. In severe cases of necrosis, treatment through debridement or amputation of the affected tissue, limb, breast or penis has been reported. Careful diagnosis is required to determine whether necrosis is caused by an underlying disease. Warfarin therapy should be discontinued when warfarin is suspected to be the cause of developing necrosis and heparin therapy may be considered for anticoagulation. Although various treatments have been attempted, no treatment for necrosis has been considered uniformly effective. The following information on predisposing conditions. These and other risks associated with anticoagulant therapy must be weighed against the risk of thrombosis or embolization in untreated cases.
It cannot be emphasized too strongly that treatment of each patient is a highly individualized matter. Dosage should be controlled by periodic determinations of prothrombin time (PT) or other suitable coagulation tests. Determinations of whole blood clotting and bleeding times are not effective measures for control of therapy. Heparin prolongs the 1-stage PT. When heparin and Coumadin are administered concomitantly, refer to conversion from heparin therapy for recommendations.
Caution should be observed when Coumadin is administered in any situation or in the presence of any predisposing condition where added risk of hemorrhage or necrosis is present.
Anticoagulation therapy with Coumadin may enhance the release of atheromatous plaque emboli, thereby increasing the risk of complications from systemic cholesterol microembolization, including the "purple toes syndrome." Discontinuation of Coumadin therapy is recommended when such phenomena are observed.
Systemic atheroemboli and cholesterol microemboli can present with a variety of signs and symptoms including purple toes syndrome, livedo reticularis, rash, gangrene, abrupt and intense pain in the leg, foot or toes, foot ulcers, myalgia, penile gangrene, abdominal pain, flank or back pain, hematuria, renal insufficiency, hypertension, cerebral ischemia, spinal cord infarction, pancreatitis, symptoms stimulating polyarteritis, or any other sequelae of vascular compromise due to embolic occlusion. The most commonly involved visceral organs are the kidneys followed by the pancreas, spleen and liver. Some cases have progressed to necrosis or death.
Purple toes syndrome is a complication of oral anticoagulation characterized by a dark, purplish or mottled color of the toes, usually occurring between 3-10 weeks, or later, after the initiation of therapy with warfarin or related compounds. Major features of this syndrome include purple color of plantar surfaces and sides of the toes that blanches on moderate pressure and fades with elevation of the legs; pain and tenderness of the toes; waxing and waning of the color over time. While the purple toes syndrome is reported to be reversible, some cases progress to gangrene or necrosis which may require debridement of the affected area or may lead to amputation.
The decision to administer anticoagulants in the following conditions must be based upon clinical judgment in which the risks of anticoagulant therapy are weighed against the benefits.
Use in lactation: Coumadin appears in the milk of nursing mothers in an inactive form. Infants nursed by Coumadin-treated mothers had no change in prothrombin times (PTs). Effects in premature infants have not been evaluated.
Severe to moderate hepatic or renal insufficiency.
Infectious diseases or disturbances of gastrointestinal flora (sprue, antibiotic therapy).
Trauma which may result in internal bleeding.
Surgery or trauma resulting in large exposed raw surfaces.
Indwelling catheters.
Severe to moderate hypertension.
Known or Suspected Deficiency in Protein C: This hereditary or acquired condition, which should be suspected if there is a history of recurrent episodes of thromboembolic disorders in the patient or in the family, has been associated with an increased risk of developing necrosis following warfarin administration. Tissue necrosis may occur in the absence of protein C deficiency. It has been reported that concurrent anticoagulation therapy with heparin for 5-7 days during initiation of therapy with Coumadin may minimize the incidence of this reaction. Warfarin therapy should be discontinued when warfarin is suspected to be the cause of developing necrosis and heparin therapy may be considered for anticoagulation.
Miscellaneous: Polycythemia vera, vasculitis, severe diabetes, severe allergic and anaphylactic disorders.
Patients with congestive heart failure may become more sensitive to Coumadin, thereby requiring more frequent laboratory monitoring and reduced doses of Coumadin.
Concurrent use of anticoagulants with streptokinase or urokinase is not recommended and may be hazardous. (Please note recommendations accompanying these preparations.)
It cannot be emphasized too strongly that treatment of each patient is a highly individualized matter. Dosage should be controlled by periodic determinations of prothrombin time (PT) or other suitable coagulation tests. Determinations of whole blood clotting and bleeding times are not effective measures for control of therapy. Heparin prolongs the 1-stage PT. When heparin and Coumadin are administered concomitantly, refer to conversion from heparin therapy for recommendations.
Caution should be observed when Coumadin is administered in any situation or in the presence of any predisposing condition where added risk of hemorrhage or necrosis is present.
Anticoagulation therapy with Coumadin may enhance the release of atheromatous plaque emboli, thereby increasing the risk of complications from systemic cholesterol microembolization, including the "purple toes syndrome." Discontinuation of Coumadin therapy is recommended when such phenomena are observed.
Systemic atheroemboli and cholesterol microemboli can present with a variety of signs and symptoms including purple toes syndrome, livedo reticularis, rash, gangrene, abrupt and intense pain in the leg, foot or toes, foot ulcers, myalgia, penile gangrene, abdominal pain, flank or back pain, hematuria, renal insufficiency, hypertension, cerebral ischemia, spinal cord infarction, pancreatitis, symptoms stimulating polyarteritis, or any other sequelae of vascular compromise due to embolic occlusion. The most commonly involved visceral organs are the kidneys followed by the pancreas, spleen and liver. Some cases have progressed to necrosis or death.
Purple toes syndrome is a complication of oral anticoagulation characterized by a dark, purplish or mottled color of the toes, usually occurring between 3-10 weeks, or later, after the initiation of therapy with warfarin or related compounds. Major features of this syndrome include purple color of plantar surfaces and sides of the toes that blanches on moderate pressure and fades with elevation of the legs; pain and tenderness of the toes; waxing and waning of the color over time. While the purple toes syndrome is reported to be reversible, some cases progress to gangrene or necrosis which may require debridement of the affected area or may lead to amputation.
The decision to administer anticoagulants in the following conditions must be based upon clinical judgment in which the risks of anticoagulant therapy are weighed against the benefits.
Use in lactation: Coumadin appears in the milk of nursing mothers in an inactive form. Infants nursed by Coumadin-treated mothers had no change in prothrombin times (PTs). Effects in premature infants have not been evaluated.
Severe to moderate hepatic or renal insufficiency.
Infectious diseases or disturbances of gastrointestinal flora (sprue, antibiotic therapy).
Trauma which may result in internal bleeding.
Surgery or trauma resulting in large exposed raw surfaces.
Indwelling catheters.
Severe to moderate hypertension.
Known or Suspected Deficiency in Protein C: This hereditary or acquired condition, which should be suspected if there is a history of recurrent episodes of thromboembolic disorders in the patient or in the family, has been associated with an increased risk of developing necrosis following warfarin administration. Tissue necrosis may occur in the absence of protein C deficiency. It has been reported that concurrent anticoagulation therapy with heparin for 5-7 days during initiation of therapy with Coumadin may minimize the incidence of this reaction. Warfarin therapy should be discontinued when warfarin is suspected to be the cause of developing necrosis and heparin therapy may be considered for anticoagulation.
Miscellaneous: Polycythemia vera, vasculitis, severe diabetes, severe allergic and anaphylactic disorders.
Patients with congestive heart failure may become more sensitive to Coumadin, thereby requiring more frequent laboratory monitoring and reduced doses of Coumadin.
Concurrent use of anticoagulants with streptokinase or urokinase is not recommended and may be hazardous. (Please note recommendations accompanying these preparations.)
Special Precautions
Periodic determination of PT or other suitable coagulation test is essential.
Numerous factors, alone or in combination, including travel, changes in diet, environment, physical state and medication may influence response of the patient to anticoagulants. It is generally good practice to monitor the patient's response with additional PT determinations in the period immediately after discharge from the hospital, and whenever other medications are initiated, discontinued or taken haphazardly. The following factors are listed for reference; however, other factors may also affect the anticoagulant response.
The following factors, alone or in combination, may be responsible for increased PT response: Endogenous Factors: Cancer; collagen disease; congestive heart failure; diarrhea; elevated temperature; hepatic disorders (infectious hepatitis, jaundice); hyperthyroidism; poor nutritional state; steatorrhea and vitamin K deficiency.
Exogenous Factors: Acetaminophen, alcohol*; allopurinol; aminosalicylic acid; amiodarone HCl; anabolic steroids; anesthetics (inhalation), antibiotics; bromelains; chenodiol, chloral hydrate*; chlorpropamide; chymotrypsin; cimetidine; clofibrate; Coumadin overdosage; dextran; dextrothyroxine; diazoxide; diflunisal; diuretics*; disulfiram; ethacrynic acid; fenoprofen; fluoroquinolone antibiotics, glucagon; hepatotoxic drugs; ibuprofen, indomethacin; influenza virus vaccine; lovastatin, mefenamic acid; methyldopa; methylphenidate; metronidazole, miconazole; MAOIs; moricizine HCl*; nalidixic acid; naproxen; pentoxifylline; phenylbutazone; phenytoin; prolonged narcotics; propafenone, pyrazolones, quinidine, quinine; ranitidine*; salicylates; sulfinpyrazone; long-acting sulfonamides; sulindac; tamoxifen, thyroid drugs; tolbutamide; trimethoprim/sulfamethoxazole; also, other medications affecting blood elements which may modify hemostasis; dietary deficiencies; prolonged hot weather, unreliable PT determinations.
*Increased and decreased PT responses have been reported.
The following factors, alone or in combination, may be responsible for decreased PT response: Endogenous Factors: Edema; hereditary coumarin resistance; hyperlipemia; hypothyroidism.
Exogenous Factors: Adrenocortical steroids; alcohol*; aminoglutethimide, antacids; antihistamines; barbiturates; carbamazepine; chloral hydrate*; chlordiazepoxide; cholestyramine; Coumadin underdosage; diuretics*; ethchlorvynol; glutethimide; griseofulvin; haloperidol; meprobamate; moricizine HCl*, nafcillin, oral contraceptives; paraldehyde; primidone; ranitidine*; rifampin; sucralfate, trazodone, vitamin C; also, diet high in vitamin K; unreliable PT determinations.
*Increased and decreased PT responses have been reported.
Because a patient may be exposed to a combination of the previously mentioned factors, the net effect of Coumadin on PT response may be unpredictable. More frequent PT monitoring is therefore advisable.
Medications of unknown interaction with coumarins are best regarded with caution when these medications are started or stopped, more frequent PT monitoring is advisable.
Coumarins may also affect the action of other drugs. Hypoglycemic agents (chlorpropamide and tolbutamide) and anticonvulsants (phenytoin and phenobarbital) may accumulate in the body as a result of interference with either their metabolism or excretion.
It has been reported that concomitant administration of warfarin and ticlopidine may be associated with cholestatic hepatitis.
Special Risk Patients: Caution should be observed when warfarin sodium is administered to certain patients eg, the elderly or debilitated or when administered in any situation or physical condition where added risk of hemorrhage is present.
Intramuscular (IM) injections of concomitant medications should be confined to the upper extremities which permits easy access for manual compression, inspections for bleeding and use of pressure bandages.
Caution should be observed when Coumadin (or warfarin) is administered concomitantly with nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, to be certain that no change in anticoagulation dosage is required. In addition to specific drug interactions that might affect PT, NSAIDs, including aspirin, can inhibit platelet aggregation and can cause gastrointestinal bleeding, peptic ulceration and/or perforation.
Information for Patients: The objective of anticoagulant therapy is to control the coagulation mechanism so that thrombosis is prevented while avoiding spontaneous bleeding. Effective therapeutic levels with minimal complications are in part dependent upon cooperative and well-instructed patients who communicate effectively with their physician. Various Coumadin patient educational guides are available to physicians on request.
Patients should be advised: Strict adherence to prescribed dosage schedule is necessary. Do not take or discontinue any other medication, except on advice of physician. Avoid alcohol, salicylates (eg, aspirin and topical analgesics), large amounts of green leafy vegetables and/or drastic changes in dietary habits, which may affect Coumadin therapy. Coumadin may cause a red-orange discoloration of alkaline urine. The patient should notify the physician if any illness eg, diarrhea, infection or fever develops or if any unusual symptoms eg, pain, swelling or discomfort appear or if prolonged bleeding from cuts, increased menstrual flow or vaginal bleeding, nosebleeds or bleeding of gums from brushing, unusual bleeding or bruising, red or dark brown urine, red or tar black stools or diarrhea occurs.
Carcinogenicity, Mutagenicity & Impairment of Fertility: Carcinogenicity and mutagenicity studies have not been performed with Coumadin. The reproductive effects of Coumadin have not been evaluated.
Use in pregnancy: Pregnancy Category X: See Contraindications.
Use in children: Safety and effectiveness in children <18 years have not been established.
Numerous factors, alone or in combination, including travel, changes in diet, environment, physical state and medication may influence response of the patient to anticoagulants. It is generally good practice to monitor the patient's response with additional PT determinations in the period immediately after discharge from the hospital, and whenever other medications are initiated, discontinued or taken haphazardly. The following factors are listed for reference; however, other factors may also affect the anticoagulant response.
The following factors, alone or in combination, may be responsible for increased PT response: Endogenous Factors: Cancer; collagen disease; congestive heart failure; diarrhea; elevated temperature; hepatic disorders (infectious hepatitis, jaundice); hyperthyroidism; poor nutritional state; steatorrhea and vitamin K deficiency.
Exogenous Factors: Acetaminophen, alcohol*; allopurinol; aminosalicylic acid; amiodarone HCl; anabolic steroids; anesthetics (inhalation), antibiotics; bromelains; chenodiol, chloral hydrate*; chlorpropamide; chymotrypsin; cimetidine; clofibrate; Coumadin overdosage; dextran; dextrothyroxine; diazoxide; diflunisal; diuretics*; disulfiram; ethacrynic acid; fenoprofen; fluoroquinolone antibiotics, glucagon; hepatotoxic drugs; ibuprofen, indomethacin; influenza virus vaccine; lovastatin, mefenamic acid; methyldopa; methylphenidate; metronidazole, miconazole; MAOIs; moricizine HCl*; nalidixic acid; naproxen; pentoxifylline; phenylbutazone; phenytoin; prolonged narcotics; propafenone, pyrazolones, quinidine, quinine; ranitidine*; salicylates; sulfinpyrazone; long-acting sulfonamides; sulindac; tamoxifen, thyroid drugs; tolbutamide; trimethoprim/sulfamethoxazole; also, other medications affecting blood elements which may modify hemostasis; dietary deficiencies; prolonged hot weather, unreliable PT determinations.
*Increased and decreased PT responses have been reported.
The following factors, alone or in combination, may be responsible for decreased PT response: Endogenous Factors: Edema; hereditary coumarin resistance; hyperlipemia; hypothyroidism.
Exogenous Factors: Adrenocortical steroids; alcohol*; aminoglutethimide, antacids; antihistamines; barbiturates; carbamazepine; chloral hydrate*; chlordiazepoxide; cholestyramine; Coumadin underdosage; diuretics*; ethchlorvynol; glutethimide; griseofulvin; haloperidol; meprobamate; moricizine HCl*, nafcillin, oral contraceptives; paraldehyde; primidone; ranitidine*; rifampin; sucralfate, trazodone, vitamin C; also, diet high in vitamin K; unreliable PT determinations.
*Increased and decreased PT responses have been reported.
Because a patient may be exposed to a combination of the previously mentioned factors, the net effect of Coumadin on PT response may be unpredictable. More frequent PT monitoring is therefore advisable.
Medications of unknown interaction with coumarins are best regarded with caution when these medications are started or stopped, more frequent PT monitoring is advisable.
Coumarins may also affect the action of other drugs. Hypoglycemic agents (chlorpropamide and tolbutamide) and anticonvulsants (phenytoin and phenobarbital) may accumulate in the body as a result of interference with either their metabolism or excretion.
It has been reported that concomitant administration of warfarin and ticlopidine may be associated with cholestatic hepatitis.
Special Risk Patients: Caution should be observed when warfarin sodium is administered to certain patients eg, the elderly or debilitated or when administered in any situation or physical condition where added risk of hemorrhage is present.
Intramuscular (IM) injections of concomitant medications should be confined to the upper extremities which permits easy access for manual compression, inspections for bleeding and use of pressure bandages.
Caution should be observed when Coumadin (or warfarin) is administered concomitantly with nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, to be certain that no change in anticoagulation dosage is required. In addition to specific drug interactions that might affect PT, NSAIDs, including aspirin, can inhibit platelet aggregation and can cause gastrointestinal bleeding, peptic ulceration and/or perforation.
Information for Patients: The objective of anticoagulant therapy is to control the coagulation mechanism so that thrombosis is prevented while avoiding spontaneous bleeding. Effective therapeutic levels with minimal complications are in part dependent upon cooperative and well-instructed patients who communicate effectively with their physician. Various Coumadin patient educational guides are available to physicians on request.
Patients should be advised: Strict adherence to prescribed dosage schedule is necessary. Do not take or discontinue any other medication, except on advice of physician. Avoid alcohol, salicylates (eg, aspirin and topical analgesics), large amounts of green leafy vegetables and/or drastic changes in dietary habits, which may affect Coumadin therapy. Coumadin may cause a red-orange discoloration of alkaline urine. The patient should notify the physician if any illness eg, diarrhea, infection or fever develops or if any unusual symptoms eg, pain, swelling or discomfort appear or if prolonged bleeding from cuts, increased menstrual flow or vaginal bleeding, nosebleeds or bleeding of gums from brushing, unusual bleeding or bruising, red or dark brown urine, red or tar black stools or diarrhea occurs.
Carcinogenicity, Mutagenicity & Impairment of Fertility: Carcinogenicity and mutagenicity studies have not been performed with Coumadin. The reproductive effects of Coumadin have not been evaluated.
Use in pregnancy: Pregnancy Category X: See Contraindications.
Use in children: Safety and effectiveness in children <18 years have not been established.
Use In Pregnancy & Lactation
Use in pregnancy: Pregnancy Category X: See Contraindications.
Use in lactation: Coumadin appears in the milk of nursing mothers in an inactive form. Infants nursed by Coumadin-treated mothers had no change in prothrombin times (PTs). Effects in premature infants have not been evaluated.
Use in lactation: Coumadin appears in the milk of nursing mothers in an inactive form. Infants nursed by Coumadin-treated mothers had no change in prothrombin times (PTs). Effects in premature infants have not been evaluated.
Adverse Reactions
Potential adverse reactions to Coumadin may include:
Hemorrhage from any tissue or organ. This is a consequence of the anticoagulant effect. The signs and symptoms will vary according to the location and degree or extent of the bleeding. Hemorrhagic complications may present as paralysis; headache, chest, abdomen, joint or other pain; shortness of breath, difficult breathing or swallowing; unexplained swelling; or unexplained shock. Therefore, the possibility of hemorrhage should be considered in evaluating the condition of any anticoagulated patient with complaints which do not indicate an obvious diagnosis. Bleeding during anticoagulant therapy does not always correlate with prothrombin activity (see Treatment under Overdosage).
Bleeding which occurs when the PT is within the therapeutic range warrants diagnostic investigation since it may unmask a previously unsuspected lesion eg, tumor, ulcer, etc.
Necrosis of skin and other tissues (see Warnings).
Other adverse reactions are infrequent and consist of alopecia, urticaria, dermatitis, fever, nausea, diarrhea, abdominal cramping, systemic cholesterol microembolization, purple toes syndrome, cholestatic hepatic injury and hypersensitivity reactions.
Priapism has been associated with anticoagulant administration; however, a causal relationship has not been established.
Hemorrhage from any tissue or organ. This is a consequence of the anticoagulant effect. The signs and symptoms will vary according to the location and degree or extent of the bleeding. Hemorrhagic complications may present as paralysis; headache, chest, abdomen, joint or other pain; shortness of breath, difficult breathing or swallowing; unexplained swelling; or unexplained shock. Therefore, the possibility of hemorrhage should be considered in evaluating the condition of any anticoagulated patient with complaints which do not indicate an obvious diagnosis. Bleeding during anticoagulant therapy does not always correlate with prothrombin activity (see Treatment under Overdosage).
Bleeding which occurs when the PT is within the therapeutic range warrants diagnostic investigation since it may unmask a previously unsuspected lesion eg, tumor, ulcer, etc.
Necrosis of skin and other tissues (see Warnings).
Other adverse reactions are infrequent and consist of alopecia, urticaria, dermatitis, fever, nausea, diarrhea, abdominal cramping, systemic cholesterol microembolization, purple toes syndrome, cholestatic hepatic injury and hypersensitivity reactions.
Priapism has been associated with anticoagulant administration; however, a causal relationship has not been established.
Drug Interactions
Antiarrhythmics, oral aminoglycosides, parenteral cephalosporins, macrolides, high-dose IV penicillins, quinolones, long-acting sulfonamides, tetracyclines, anticonvulsants, antidepressants, antineoplastics, antithyroid drugs, diuretics, systemic fungal medications, gastric acidity & peptic ulcer agents, hypnotics, bile acid binding resins, adrenocortical steroids, TB agents, vit. Bromelains, danshen, dong quai (Angelica sinensis), garlic, Ginkgo biloba, ginseng, cranberry products; co-enzyme Q10 & St. John's wort.
Storage
Store at controlled room temperature (59-86°F, 15-30°C). Protect from light. Dispense in a tight, light-resistant container as defined in the USP.
Action
Pharmacotherapeutic Group: Anticoagulant.
Pharmacology: Coumadin and other coumarin anticoagulants act by inhibiting the synthesis of vitamin K-dependent coagulation factors. The resultant in vivo effect is a sequential depression of Factors VII, IX, X and II activities. The degree of depression is dependent upon the dosage administered. Anticoagulants have no direct effect on an established thrombus, nor do they reverse ischemic tissue damage. However, once a thrombus has occurred, the goal of anticoagulant treatment is to prevent further extension of the formed clot and prevent secondary thromboembolic complications which may result in serious and possible fatal sequelae.
Pharmacokinetics: After oral administration of Coumadin, absorption is essentially complete, and maximal plasma concentrations (Cmax) are reached in 1-9 hrs. Approximately 97% is bound to albumin within the plasma. An anticoagulant effect generally occurs within 24 hrs. However, peak anticoagulant effect may be delayed 72-96 hrs and its duration of action may persist for 4-5 days, thus producing a smooth and long-lasting response curve. Coumadin is metabolized by hepatic microsomal enzymes to inactive metabolites that are excreted into the bile, reabsorbed and excreted into the urine.
Coumadin is a potent drug with a t½ of 2½ days; therefore its effects may become more pronounced as daily maintenance doses overlap.
Pharmacology: Coumadin and other coumarin anticoagulants act by inhibiting the synthesis of vitamin K-dependent coagulation factors. The resultant in vivo effect is a sequential depression of Factors VII, IX, X and II activities. The degree of depression is dependent upon the dosage administered. Anticoagulants have no direct effect on an established thrombus, nor do they reverse ischemic tissue damage. However, once a thrombus has occurred, the goal of anticoagulant treatment is to prevent further extension of the formed clot and prevent secondary thromboembolic complications which may result in serious and possible fatal sequelae.
Pharmacokinetics: After oral administration of Coumadin, absorption is essentially complete, and maximal plasma concentrations (Cmax) are reached in 1-9 hrs. Approximately 97% is bound to albumin within the plasma. An anticoagulant effect generally occurs within 24 hrs. However, peak anticoagulant effect may be delayed 72-96 hrs and its duration of action may persist for 4-5 days, thus producing a smooth and long-lasting response curve. Coumadin is metabolized by hepatic microsomal enzymes to inactive metabolites that are excreted into the bile, reabsorbed and excreted into the urine.
Coumadin is a potent drug with a t½ of 2½ days; therefore its effects may become more pronounced as daily maintenance doses overlap.
MedsGo Class
Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)
Features
Brand
Coumadin
Full Details
Dosage Strength
2.5 mg
Drug Ingredients
- Warfarin
Drug Packaging
Tablet 1's
Generic Name
Warfarin Sodium Clathrate
Dosage Form
Tablet
Registration Number
DR-3744
Drug Classification
Prescription Drug (RX)
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