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WARFARIN SODIUM tablet
[Bryant Ranch Prepack]


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HUMAN PRESCRIPTION DRUG LABEL Abbreviated New Drug Application
Drug Label Sections

Warfarin sodium can cause major or fatal bleeding. Bleeding is more likely to occur during the starting period and with a higher dose (resulting in a higher INR). Risk factors for bleeding include high intensity of anticoagulation (INR >4.0), age ≥65, highly variable INRs, history of gastrointestinal bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, malignancy, trauma, renal insufficiency, concomitant drugs (see ), and long duration of warfarin therapy. Regular monitoring of INR should be performed on all treated patients. Those at high risk of bleeding may benefit from more frequent INR monitoring, careful dose adjustment to desired INR, and a shorter duration of therapy. Patients should be instructed about prevention measures to minimize risk of bleeding and to report immediately to physicians signs and symptoms of bleeding (see ). BLEEDING WARNING:PRECAUTIONSPRECAUTIONS: Information for Patients

DESCRIPTION

Crystalline warfarin sodium is an anticoagulant which acts by inhibiting vitamin K-dependent coagulation factors. Chemically, it is 3-(α-acetonylbenzyl)-4-hydroxycoumarin sodium salt and is a racemic mixture of the - and -enantiomers. Crystalline warfarin sodium is an isopropanol clathrate. The crystallization of warfarin sodium virtually eliminates trace impurities present in amorphous warfarin. Its empirical formula is C H NaO , and its structural formula may be represented by the following: RS19154

Chemical Structure - Warfarin

Crystalline warfarin sodium occurs as a white, odorless, crystalline powder, is discolored by light and is very soluble in water; freely soluble in alcohol; very slightly soluble in chloroform and in ether.

Warfarin Sodium Tablets, USP for oral use also contain:

All strengths:Anhydrous lactose, corn starch and magnesium stearate
1 mg:D&C red #6 Barium Lake.
2 mg:FD&C blue #2 Aluminum Lake, FD&C red #40 Aluminum Lake.
2.5 mg:FD&C blue #2 Aluminum Lake, D&C yellow #10 Aluminum Lake.
3 mg:FD&C blue #2 Aluminum Lake, FD&C red #40 Aluminum Lake, D&C yellow #10 Aluminum Lake.
4 mg:FD&C blue #1 Aluminum Lake.
5 mg:D&C yellow #10 Aluminum Lake, D&C red #6 Barium Lake.
6 mg:D&C yellow #10 Aluminum Lake, FD&C blue #2 Aluminum Lake.
7.5 mg:D&C yellow #10 Aluminum Lake.
10 mg:Dye Free

CLINICAL PHARMACOLOGY

Warfarin sodium tablets, USP and other coumarin anticoagulants act by inhibiting the synthesis of vitamin K dependent clotting factors, which include Factors II, VII, IX and X, and the anticoagulant proteins C and S. Half-lives of these clotting factors are as follows: Factor II - 60 hours, VII - 4-6 hours, IX - 24 hours, and X - 48-72 hours. The half-lives of proteins C and S are approximately 8 hours and 30 hours, respectively. The resultant effect is a sequential depression of Factor VII, Protein C, Factor IX, Protein S, and Factor X and II activities. Vitamin K is an essential cofactor for the post ribosomal synthesis of the vitamin K dependent clotting factors. The vitamin promotes the biosynthesis of γ-carboxyglutamic acid residues in the proteins which are essential for biological activity. in vivo

Mechanism of Action

Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of the vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K1 epoxide. The degree of depression is dependent upon the dosage administered and, in part, by the patient's VKORC1 genotype. Therapeutic doses of warfarin decrease the total amount of the active form of each vitamin K dependent clotting factor made by the liver by approximately 30% to 50%.

An anticoagulation effect generally occurs within 24 hours after drug administration. However, peak anticoagulant effect may be delayed 72 to 96 hours. The duration of action of a single dose of racemic warfarin is 2 to 5 days. The effects of warfarin sodium tablets, USP may become more pronounced as effects of daily maintenance doses overlap. 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 possibly fatal sequelae.

Pharmacokinetics

Warfarin sodium tablets, USP is a racemic mixture of the - and -enantiomers. The -enantiomer exhibits 2-5 times more anticoagulant activity than the -enantiomer in humans, but generally has a more rapid clearance. RSSR

CLINICAL TRIALS

INDICATIONS AND USAGE

Warfarin sodium tablets, USP are indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism.

Warfarin sodium tablets, USP are indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement.

Warfarin sodium tablets, USP are indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction.

CONTRAINDICATIONS

Anticoagulation is contraindicated in any localized or general physical condition or personal circumstance in which the hazard of hemorrhage might be greater than the potential clinical benefits of anticoagulation, such as:

Pregnancy

Warfarin sodium tablets, USP are contraindicated in women who are or may become pregnant because the drug passes through the placental barrier and may cause fatal hemorrhage to the fetus . Furthermore, there have been reports of birth malformations in children born to mothers who have been treated with warfarin during pregnancy. in utero

Embryopathy characterized by nasal hypoplasia with or without stippled epiphyses (chondrodysplasia punctata) has been reported in pregnant women exposed to warfarin during the first 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 have been observed. Mental retardation, blindness, and other central nervous system abnormalities have been reported in association with second and third trimester exposure. Although rare, teratogenic reports following exposure to warfarin include urinary tract anomalies such as single kidney, asplenia, anencephaly, spina bifida, cranial nerve palsy, hydrocephalus, cardiac defects and congenital heart disease, polydactyly, deformities of toes, diaphragmatic hernia, corneal leukoma, cleft palate, cleft lip, schizencephaly, and microcephaly. in utero

Spontaneous abortion and stillbirth are known to occur and a higher risk of fetal mortality is associated with the use of warfarin. Low birth weight and growth retardation have also been reported.

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.

(1) central nervous system; (2) eye; (3) traumatic surgery resulting in large open surfaces. Recent or contemplated surgery of:

(1) gastrointestinal, genitourinary or respiratory tracts; (2) cerebrovascular hemorrhage; (3) aneurysms-cerebral, dissecting aorta; (4) pericarditis and pericardial effusions; (5) bacterial endocarditis. Bleeding tendencies associated with active ulceration or overt bleeding of:

eclampsia and preeclampsia. Threatened abortion,

Inadequate laboratory facilities.

alcoholism, psychosis or other lack of patient cooperation. Unsupervised patients with senility,

and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding. Spinal puncture

major regional, lumbar block anesthesia, malignant hypertension and known hypersensitivity to warfarin or to any other components of this product. Miscellaneous:

WARNINGS

The most serious risks associated with anticoagulant therapy with warfarin sodium are hemorrhage in any tissue or organ (see ) and, less frequently (<0.1%), necrosis and/or gangrene of skin and other tissues. 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. See below for 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. 12BLACK BOX WARNING

It cannot be emphasized too strongly that treatment of each patient is a highly individualized matter. Warfarin sodium, a narrow therapeutic range (index) drug, may be affected by factors such as other drugs and dietary vitamin K. Dosage should be controlled by periodic determinations of prothrombin time (PT)/International Normalized Ratio (INR). Determinations of whole blood clotting and bleeding times are not effective measures for control of therapy. Heparin prolongs the one-stage PT. When heparin and warfarin are administered concomitantly, refer below to for recommendations. Conversion From Heparin Therapy

Increased caution should be observed when warfarin is administered in the presence of any predisposing condition where added risk of hemorrhage, necrosis, and/or gangrene is present.

Anticoagulation therapy with warfarin 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 warfarin 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 simulating 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.

Warfarin should be used with caution in patients with heparin-induced thrombocytopenia and deep venous thrombosis. Cases of venous limb ischemia, necrosis, and gangrene have occurred in patients with heparin-induced thrombocytopenia and deep venous thrombosis when heparin treatment was discontinued and warfarin therapy was started or continued. In some patients sequelae have included amputation of the involved area and/or death . 13

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:

Based on very limited published data, warfarin has not been detected in the breast milk of mothers treated with warfarin. The same limited published data report that some breast-fed infants, whose mothers were treated with warfarin, had prolonged prothrombin times, although not as prolonged as those of the mothers. The decision to breast-feed should be undertaken only after careful consideration of the available alternatives. Women who are breast-feeding and anticoagulated with warfarin should be very carefully monitored so that recommended PT/INR values are not exceeded. It is prudent to perform coagulation tests and to evaluate vitamin K status in infants before advising women taking warfarin to breast-feed. Effects in premature infants have not been evaluated. Lactation:

Severe to moderate hepatic or renal insufficiency.

sprue, antibiotic therapy. Infectious diseases or disturbances of intestinal fora:

which may result in internal bleeding. Trauma

resulting in large exposed raw surfaces. Surgery or trauma

Indwelling catheters.

Severe to moderate hypertension.

Hereditary or acquired deficiencies of protein C or its cofactor, protein S, have been associated with tissue necrosis following warfarin administration. Not all patients with these conditions develop necrosis, and tissue necrosis occurs in patients without these deficiencies. Inherited resistance to activated protein C has been described in many patients with venous thromboembolic disorders but has not yet been evaluated as a risk factor for tissue necrosis. The risk associated with these conditions, both for recurrent thrombosis and for adverse reactions, is difficult to evaluate since it does not appear to be the same for everyone. Decisions about testing and therapy must be made on an individual basis. It has been reported that concomitant anticoagulation therapy with heparin for 5 to 7 days during initiation of therapy with warfarin may minimize the incidence of tissue necrosis. Warfarin therapy should be discontinued when warfarin is suspected to be the cause of developing necrosis, and heparin therapy may be considered for anticoagulation. Known or suspected deficiency in protein C mediated anticoagulant response:

polycythemia vera, vasculitis, and severe diabetes. Miscellaneous:

PRECAUTIONS

.) Periodic determination of PT/INR is essential. (see DOSAGE AND ADMINISTRATION: Laboratory Control

Numerous factors, alone or in combination including changes in diet, medications, botanicals, and genetic variations in the CYP2C9 and VKORC1 enzymes (see ) may influence the response of the patient to warfarin. CLINICAL PHARMACOLOGY: Pharmacogenomics

Drug-Drug and Drug-Disease Interactions

It is generally good practice to monitor the patient's response with additional PT/INR determinations in the period immediately after discharge from the hospital, and whenever other medications, including botanicals, are initiated, discontinued or taken irregularly. The following factors are listed for reference; however, other factors may also affect the anticoagulant response.

Drugs may interact with warfarin through pharmacodynamic or pharmacokinetic mechanisms. Pharmacodynamic mechanisms for drug interactions with warfarin are synergism (impaired hemostasis, reduced clotting factor synthesis), competitive antagonism (vitamin K), and altered physiologic control loop for vitamin K metabolism (hereditary resistance). Pharmacokinetic mechanisms for drug interactions with warfarin are mainly enzyme induction, enzyme inhibition, and reduced plasma protein binding. It is important to note that some drugs may interact by more than one mechanism.

The following factors, alone or in combination, may be responsible for INCREASED PT/INR response:

ENDOGENOUS FACTORS:

blood dyscrasias - see cancer collagen vascular disease congestive heart failure
CONTRAINDICATIONS


diarrhea elevated temperature hepatic disorders infectious hepatitis jaundice



hyperthyroidism poor nutritional state steatorrhea vitamin K deficiency


EXOGENOUS FACTORS:

Potential drug interactions with warfarin sodium are listed below by drug class and by specific drugs.

Classes of Drugs
5-lipoxygenase Inhibitor Adrenergic Stimulants, Central Alcohol Abuse Reduction Preparations Analgesics Anesthetics, Inhalation Antiandrogen Antiarrhythmics† Antibiotics† Aminoglycosides (oral) Cephalosporins, parenteral Macrolides Miscellaneous Penicillins, intravenous, high dose Quinolones (fluoroquinolones) Sulfonamides, long acting Tetracyclines Anticoagulants Anticonvulsants† Antidepressants† Antimalarial Agents Antineoplastics† Antiparasitic/Antimicrobials























Antiplatelet Drugs/Effects Antithyroid Drugs† Beta-Adrenergic Blockers Cholelitholytic Agents Diabetes Agents, Oral Diuretics† Fungal Medications, Intravaginal, Systemic† Gastric Acidity and Peptic Ulcer Agents† Gastrointestinal Prokinetic Agents Ulcerative Colitis Agents Gout Treatment Agents Hemorrheologic Agents Hepatotoxic Drugs Hyperglycemic Agents Hypertensive Emergency Agents Hypnotics† Hypolipidemics† Bile Acid-Binding Resins† Fibric Acid Derivatives HMG-CoA Reductase Inhibitors†























Leukotriene Receptor Antagonist Monoamine Oxidase Inhibitors Narcotics, prolonged Nonsteroidal Anti- Inflammatory Agents Proton Pump Inhibitors Psychostimulants Pyrazolones Salicylates Selective Serotonin Reuptake Inhibitors Steroids, Adrenocortical† Steroids, Anabolic (17-Alkyl Testosterone Derivatives) Thrombolytics Thyroid Drugs Tuberculosis Agents† Uricosuric Agents Vaccines Vitamins†




















Specific Drugs Reported
also: other medications affecting blood elements which may modify hemostasis dietary deficiencies prolonged hot weather unreliable PT/INR determinations †Increased and decreased PT/INR responses have been reported.



acetaminophen alcohol† allopurinol aminosalicylic acid amiodarone HCl argatroban aspirin atenolol atorvastatin† azithromycin bivalirudin capecitabine cefamandole cefazolin cefoperazone cefotetan cefoxitin ceftriaxone celecoxib cerivastatin chenodiol chloramphenicol chloral hydrate† chlorpropamide cholestyramine† cimetidine ciprofloxacin cisapride clarithromycin clofibrate cyclophosphamide† danazol dextran dextrothyroxine diazoxide

































diclofenac dicumarol diflunisal disulfiram doxycycline erythromycin esomeprazole ethacrynic acid ezetimibe fenofibrate fenoprofen fluconazole fluorouracil fluoxetine flutamide fluvastatin fluvoxamine gefitinib gemifibrozil glucagon halothane heparin ibuprofen ifosfamide indomethacin influenza virus vaccine itraconazole ketoprofen ketorolac lansoprazole lepirudin levamisole levofloxacin levothyroxine liothyronine

































lovastatin mefenamic acid methimazole† methyldopa methylphenidate methylsalicylate ointment (topical) metronidazole miconazole (intravaginal, oral, systemic) moricizine hydrochloride† nalidixic acid naproxen neomycin norfloxacin ofloxacin olsalazine omeprazole oxandrolone oxaprozin oxymetholone pantoprazole paroxetine penicillin G, intravenous pentoxifylline phenylbutazone phenytoin† piperacillin piroxicam pravastatin† prednisone† propafenone

































propoxyphene propranolol propylthiouracil† quinidine quinine rabeprazole ranitidine† rofecoxib sertraline simvastatin stanozolol streptokinase sulfamethizole sulfamethoxazole sulfinpyrazone sulfisoxazole sulindac tamoxifen tetracycline thyroid ticarcillin ticlopidine tissue plasminogen activator (t-PA) tolbutamide tramadol trimethoprim/ sulfamethoxazole urokinase valdecoxib valproate vitamin E warfarin overdose zafirlukast zileuton

































The following factors, alone or in combination, may be responsible for DECREASED PT/INR response:

ENDOGENOUS FACTORS:

edema hereditary coumarin resistance hyperlipemia

hypothyroidism nephrotic syndrome

EXOGENOUS FACTORS:

Potential drug interactions with warfarin sodium are listed below by drug class and by specific drugs.

Classes of Drugs
Adrenal Cortical Steroid Inhibitors Antacids Antianxiety Agents Antiarrhythmics† Antibiotics† Anticonvulsants† Antidepressants† Antihistamines Antineoplastics†








Antipsychotic Medications Antithyroid Drugs† Barbiturates Diuretics† Enteral Nutritional Supplements Fungal Medications, Systemic† Gastric Acidity and Peptic Ulcer Agents† Hypnotics†








Hypolipidemics† Bile Acid-Binding Resins† HMG-CoA Reductase Inhibitors† Immunosuppressives Oral Contraceptives, Estrogen Containing Selective Estrogen Receptor Modulators Steroids, Adrenocortical† Tuberculosis Agents† Vitamins†









Specific Drugs Reported
also: diet high in vitamin K unreliable PT/INR determinations †Increased and decreased PT/INR responses have been reported.

alcohol† aminoglutethimide amobarbital atorvastatin† azathioprine butabarbital butalbital carbamazepine chloral hydrate† chlordiazepoxide chlorthalidone









cholestyramine† clozapine corticotropin cortisone cyclophosphamide† dicloxacillin ethchlorvynol glutethimide griseofulvin haloperidol meprobamate









6-mercaptopurine methimazole† moricizine hydrochloride† nafcillin paraldehyde pentobarbital phenobarbital phenytoin† pravastatin† prednisone† primidone









propylthiouracil† raloxifene ranitidine† rifampin secobarbital spironolactone sucralfate trazodone vitamin C (high dose) vitamin K warfarin underdosage









Because a patient may be exposed to a combination of the above factors, the net effect of warfarin sodium on PT/INR response may be unpredictable. More frequent PT/INR 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/INR monitoring is advisable.

It has been reported that concomitant administration of warfarin and ticlopidine may be associated with cholestatic hepatitis.

Information for Patients

The objective of anticoagulant therapy is to decrease the clotting ability of the blood 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. Patients should be advised: Strict adherence to prescribed dosage schedule is necessary. Do not take or discontinue any other medication, including salicylates (e.g., aspirin and topical analgesics), other over-the-counter medications and botanical (herbal) products except on advice of the physician. Avoid alcohol consumption. Do not take warfarin during pregnancy and do not become pregnant while taking it (see ). Avoid any activity or sport that may result in traumatic injury. Prothrombin time tests and regular visits to physician or clinic are needed to monitor therapy. Carry identification stating that warfarin is being taken. If the prescribed dose of warfarin is forgotten, notify the physician immediately. Take the dose as soon as possible on the same day but do not take a double dose of warfarin the next day to make up for missed doses. The amount of vitamin K in food may affect therapy with warfarin. Eat a normal, balanced diet maintaining a consistent amount of vitamin K. Avoid drastic changes in dietary habits, such as eating large amounts of green leafy vegetables. You should also avoid intake of cranberry juice or any other cranberry products. Notify your health care provider if any of these products are part of your normal diet. Contact physician to report any illness, such as diarrhea, infection or fever. Notify physician immediately if any unusual bleeding or symptoms occur. Signs and symptoms of bleeding include: pain, swelling or discomfort, prolonged bleeding from cuts, increased menstrual flow or vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or dark brown urine, red or tar black stools, headache, dizziness, or weakness. If therapy with warfarin is discontinued, patients should be cautioned that the anticoagulant effects of warfarin may persist for about 2 to 5 days. A Medication Guide should be available to patients when their prescriptions for warfarin sodium are issued CONTRAINDICATIONSPatients should be informed that all warfarin sodium, USP, products represent the same medication, and should not be taken concomitantly, as overdosage may result.14

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity and mutagenicity studies have not been performed with warfarin. The reproductive effects of warfarin have not been evaluated. The use of warfarin during pregnancy has been associated with the development of fetal malformations in humans (see ). CONTRAINDICATIONS

Use in Pregnancy

Pregnancy Category X - See . CONTRAINDICATIONS

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 18 have not been established in randomized, controlled clinical trials. However, the use of warfarin in pediatric patients is well-documented for the prevention and treatment of thromboembolic events. Difficulty achieving and maintaining therapeutic PT/INR ranges in the pediatric patient has been reported. More frequent PT/INR determinations are recommended because of possible changing warfarin requirements.

Geriatric Use

Patients 60 years or older appear to exhibit greater than expected PT/INR response to the anticoagulant effects of warfarin (see ). Warfarin is contraindicated in any unsupervised patient with senility. Caution should be observed with administration of warfarin sodium to elderly patients in any situation or physical condition where added risk of hemorrhage is present. Lower initiation and maintenance doses of warfarin are recommended for elderly patients (see ). CLINICAL PHARMACOLOGYDOSAGE AND ADMINISTRATION

ADVERSE REACTIONS

Potential adverse reactions to warfarin may include:

  • Fatal or nonfatal hemorrhage from any tissue or organ. This is a consequence of the anticoagulant effect. The signs, symptoms, and severity will vary according to the location and degree or extent of the bleeding. Hemorrhagic complications may present as paralysis; paresthesia; headache, chest, abdomen, joint, muscle or other pain; dizziness; shortness of breath, difficult breathing or swallowing; unexplained swelling; weakness; hypotension; 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 PT/INR. (See ) . OVERDOSAGE-Treatment
  • Bleeding which occurs when the PT/INR is within the therapeutic range warrants diagnostic investigation since it may unmask a previously unsuspected lesion, e.g., tumor, ulcer, etc.
  • Necrosis of skin and other tissues. (See .) WARNINGS
  • Adverse reactions reported infrequently include: hypersensitivity/allergic reactions, including anaphylactic reactions, systemic cholesterol microembolization, purple toes syndrome, hepatitis, cholestatic hepatic injury, jaundice, elevated liver enzymes, hypotension, vasculitis, edema, anemia, pallor, fever, rash, dermatitis, including bullous eruptions, urticaria, angina syndrome, chest pain, abdominal pain including cramping, flatulence/bloating, fatigue, lethargy, malaise, asthenia, nausea, vomiting, diarrhea, pain, headache, dizziness, loss of consciousness, syncope, coma, taste perversion, pruritus, alopecia, cold intolerance, and paresthesia including feeling cold and chills.

Rare events of tracheal or tracheobronchial calcification have been reported in association with long-term warfarin therapy. The clinical significance of this event is unknown.

Priapism has been associated with anticoagulant administration, however, a causal relationship has not been established.

OVERDOSAGE

DOSAGE AND ADMINISTRATION

The dosage and administration of warfarin sodium tablets, USP must be individualized for each patient according to the particular patient's PT/INR response to the drug. The dosage should be adjusted based upon the patient's PT/INR. 15,16,17,18,19The best available information supports the following recommendations for dosing of warfarin sodium tablets.

REFERENCES

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Mfd. by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel 26110 Marketed/Packaged for: GSMS, Inc. Camarillo, CA 93012

MEDICATION GUIDE

Warfarin Sodium Tablets, USP Crystalline

Read this Medication Guide before you start taking Warfarin Sodium (WARFARIN) and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. You and your healthcare provider should talk about WARFARIN when you start taking it and at regular checkups.

What is the most important information I should know about WARFARIN?

  • (See ). Take your WARFARIN exactly as prescribed to lower the chance of blood clots forming in your body."What is WARFARIN?"
  • To benefit from WARFARIN and also lower your chance for bleeding problems, you must: Warfarin is very important for your health, but it can cause serious and life-threatening bleeding problems.
    • . This blood test is called a PT/INR test. The PT/INR test checks to see how fast your blood clots. Your healthcare provider will decide what PT/INR numbers are best for you. Your dose of WARFARIN will be adjusted to keep your PT/INR in a target range for you. Get your regular blood test to check for your response to WARFARIN
    • Call your healthcare provider right away if you get any of the following signs or symptoms of bleeding problems:
      • pain, swelling or discomfort
      • headaches, dizziness, or weakness
      • unusual bruising (bruises that develop without known cause or grow in size)
      • nose bleeds
      • bleeding gums
      • bleeding from cuts takes a long time to stop
      • menstrual bleeding or vaginal bleeding that is heavier than normal
      • pink or brown urine
      • red or black stools
      • coughing up blood
      • vomiting blood or material that looks like coffee grounds
  • Many other medicines, including prescription and non-prescription medicines, vitamins and herbal supplements can interact with WARFARIN and:Tell your healthcare provider about all the medicines, vitamins and herbal supplements you take. Do not stop medicines or take anything new unless you have talked to your healthcare provider. Keep a list of your medicines with you at all times to show your healthcare provider and pharmacist.
    • affect the dose you need, or
    • increase WARFARIN side effects.
  • Do not take other medicines that contain warfarin. . Warfarin is the active ingredient in WARFARIN
  • Some foods can interact with WARFARIN and affect your treatment and dose.
    • Talk to your doctor before you make any diet changes. Leafy green vegetables contain Vitamin K. Certain vegetable oils also contain large amounts of Vitamin K. Too much Vitamin K can lower the effect of WARFARIN. Eat a normal, balanced diet.Do not eat large amounts of leafy green vegetables.
    • Avoid drinking cranberry juice or eating cranberry products.
    • Avoid drinking alcohol.
  • Always tell all of your healthcare providers that you take WARFARIN.
  • Wear or carry information that you take WARFARIN.

What is WARFARIN?

WARFARIN is an anticoagulant medicine. It is used to lower the chance of blood clots forming in your body. Blood clots can cause a stroke, heart attack, or other serious conditions such as blood clots in the legs or lungs.

Who should not take WARFARIN?

Do not take WARFARIN if:

  • . Your healthcare provider will decide if WARFARIN is right for you. Talk to your healthcare provider about all of your health conditions. your chance of having bleeding problems is higher than the possible benefit of treatment
  • WARFARIN can cause death or birth defects to an unborn baby. Use effective birth control if you can get pregnant. you are pregnant or plan to become pregnant.
  • . you are allergic to warfarin or to anything else in WARFARIN

What should I tell my healthcare provider before starting WARFARIN?

Tell your healthcare provider about all of your health conditions, including if you:

  • have bleeding problems
  • fall often
  • have liver or kidney problems
  • have high blood pressure
  • have a heart problem called congestive heart failure
  • have diabetes
  • . Alcohol can affect your WARFARIN dose and should be avoided. drink alcohol or have problems with alcohol abuse
  • . See " " are pregnant or planning to become pregnantWho should not take WARFARIN?
  • . Warfarin Sodium Tablets may increase bleeding in your baby. Talk to your doctor about the best way to feed your baby. If you choose to breastfeed while taking WARFARIN, both you and your baby should be carefully monitored for bleeding problems. are breastfeeding

See Tell your healthcare provider about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements."What is the most important information I should know about WARFARIN?"

How should I take WARFARIN?

  • Your healthcare provider will adjust your dose from time to time depending on your response to WARFARIN. Take WARFARIN exactly as prescribed.
  • You must have regular blood tests and visits with your healthcare provider to monitor your condition.
  • You can take WARFARIN either with food or on an empty stomach. Take WARFARIN at the same time every day.
  • . Take the dose as soon as possible on the same day. Do not take a double dose of WARFARIN the next day to make up for a missed dose. If you miss a dose of WARFARIN, call your healthcare provider
  • Call your healthcare provider right away if you take too many WARFARIN.
  • Call your healthcare provider if you are sick with diarrhea, an infection, or have a fever.
  • Your WARFARIN may have to be stopped for a short time or you may need your dose adjusted. Tell your healthcare provider about any planned surgeries, medical or dental procedures.
  • . Your healthcare provider may need to check you. Call your healthcare provider right away if you fall or injure yourself, especially if you hit your head

What should I avoid while taking WARFARIN?

  • Do not start, stop, or change any medicine without talking with your healthcare provider.
  • Do not make changes in your diet, such as eating large amounts of green, leafy vegetables.
  • Do not change your weight by dieting, without first checking with your healthcare provider.
  • Avoid drinking alcohol.
  • Do not do any activity or sport that may cause a serious injury.

What are the possible side effects of WARFARIN?

  • WARFARIN is very important for your health, but it can cause serious and life-threatening bleeding problems. See "What is the most important information I should know about WARFARIN?"
  • Serious side effects of WARFARIN also include:
    • . This can happen soon after starting WARFARIN. It happens because blood clots form and block blood flow to an area of your body. Call your healthcare provider right away if you have pain, color, or temperature change to any area of your body. You may need medical care right away to prevent death or loss (amputation) of your affected body part. death of skin tissue (skin necrosis or gangrene)
    • . Call your healthcare provider right away if you have pain in your toes and they look purple in color or dark in color. "purple toes syndrome"

allergic reactions, liver problems, low blood pressure, swelling, low red blood cells, paleness, fever, and rash. Call your healthcare provider if you have any side effect that bothers you. Other side effects with WARFARIN include

These are not all of the side effects of WARFARIN. For more information, ask your healthcare provider or pharmacist.

How should I store WARFARIN?

  • Store WARFARIN at room temperature between 68 and 77 F. Protect from light.
  • Keep WARFARIN and all medicines out of the reach of children.

General Information about WARFARIN

Medicines are sometimes prescribed for purposes not mentioned in a Medication Guide. Do not use WARFARIN for a condition for which it was not prescribed. Do not give WARFARIN to other people, even if they have the same condition. It may harm them.

This Medication Guide summarizes the most important information about WARFARIN. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about WARFARIN that was written for healthcare professionals.

If you would like more information, call 1-800-544-1449.

Rx only

Mfd. by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel 26110

Marketed/Packaged by: GSMS, Inc. Camarillo, CA 93012

This Medication Guide has been approved by the U.S. Food and Drug Administration.

January 2009

Warfarin Sodium 5 mg Tablet

Label Image
WARFARIN SODIUM 
warfarin sodium tablet
Product Information
Product TypeHUMAN PRESCRIPTION DRUG LABELItem Code (Source)NDC:63629-2548(NDC:51672-4032)
Route of AdministrationORALDEA Schedule    
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
WARFARIN SODIUM (WARFARIN) WARFARIN SODIUM5 mg
Inactive Ingredients
Ingredient NameStrength
ANHYDROUS LACTOSE 
STARCH, CORN 
MAGNESIUM STEARATE 
D&C YELLOW NO. 10 
D&C RED NO. 6 
Product Characteristics
Colororange (peach) Score2 pieces
ShapeOVALSize11mm
FlavorImprint Code 5;WARFARIN;TARO
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:63629-2548-1100 in 1 BOTTLE
2NDC:63629-2548-230 in 1 BOTTLE
3NDC:63629-2548-345 in 1 BOTTLE
4NDC:63629-2548-460 in 1 BOTTLE
5NDC:63629-2548-515 in 1 BOTTLE
6NDC:63629-2548-690 in 1 BOTTLE
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA04030107/15/1999
Labeler - Bryant Ranch Prepack (171714327)
Registrant - Bryant Ranch Prepack (171714327)
Establishment
NameAddressID/FEIBusiness Operations
Bryant Ranch Prepack171714327REPACK(63629-2548), RELABEL(63629-2548)

Revised: 7/2014
 
Bryant Ranch Prepack

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