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Warfarin Sodium

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Overview

What is Warfarin Sodium?

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 CHNaO, and its structural formula may be represented by the following:

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:



What does Warfarin Sodium look like?



What are the available doses of Warfarin Sodium?

Sorry No records found.

What should I talk to my health care provider before I take Warfarin Sodium?

Sorry No records found

How should I use Warfarin Sodium?

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.

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.


What interacts with Warfarin Sodium?

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.


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.


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.


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What are the warnings of Warfarin Sodium?

Prolonged use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses.

The most serious risks associated with anticoagulant therapy with warfarin sodium are hemorrhage in any tissue or organ (see ) and, less frequently (
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.

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.

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:

Lactation:

Severe to moderate hepatic or renal insufficiency.

Infectious diseases or disturbances of intestinal fora:

Trauma

Surgery or trauma

Indwelling catheters.

Severe to moderate hypertension.

Known or suspected deficiency in protein C mediated anticoagulant response:

Miscellaneous:


What are the precautions of Warfarin Sodium?

Periodic determination of PT/INR is essential. (see

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.

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:

EXOGENOUS FACTORS:

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

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

ENDOGENOUS FACTORS:

EXOGENOUS FACTORS:

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

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.

blood dyscrasias -  see cancercollagen vascular diseasecongestive heart failurediarrheaelevated temperaturehepatic disorders  infectious hepatitis  jaundicehyperthyroidismpoor nutritional statesteatorrheavitamin K deficiency
5-lipoxygenase InhibitorAdrenergic Stimulants, CentralAlcohol Abuse Reduction  PreparationsAnalgesicsAnesthetics, InhalationAntiandrogenAntiarrhythmics†Antibiotics†  Aminoglycosides (oral)  Cephalosporins, parenteral  Macrolides  Miscellaneous  Penicillins, intravenous,    high dose  Quinolones    (fluoroquinolones)  Sulfonamides, long acting  TetracyclinesAnticoagulantsAnticonvulsants†Antidepressants†Antimalarial AgentsAntineoplastics†Antiparasitic/AntimicrobialsAntiplatelet Drugs/EffectsAntithyroid Drugs†Beta-Adrenergic BlockersCholelitholytic AgentsDiabetes Agents, OralDiuretics†Fungal Medications,  Intravaginal, Systemic†Gastric Acidity and Peptic  Ulcer Agents†Gastrointestinal  Prokinetic Agents  Ulcerative Colitis AgentsGout Treatment AgentsHemorrheologic AgentsHepatotoxic DrugsHyperglycemic AgentsHypertensive Emergency  AgentsHypnotics†Hypolipidemics†  Bile Acid-Binding Resins†  Fibric Acid Derivatives  HMG-CoA Reductase    Inhibitors†Leukotriene Receptor  AntagonistMonoamine Oxidase  InhibitorsNarcotics, prolongedNonsteroidal Anti-  Inflammatory AgentsProton Pump InhibitorsPsychostimulantsPyrazolonesSalicylatesSelective Serotonin  Reuptake InhibitorsSteroids, Adrenocortical†Steroids, Anabolic (17-Alkyl  Testosterone Derivatives)ThrombolyticsThyroid DrugsTuberculosis Agents†Uricosuric AgentsVaccinesVitamins†
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.
acetaminophenalcohol†allopurinolaminosalicylic acidamiodarone HClargatrobanaspirinatenololatorvastatin†azithromycinbivalirudincapecitabinecefamandolecefazolincefoperazonecefotetancefoxitinceftriaxonecelecoxibcerivastatinchenodiolchloramphenicolchloral hydrate†chlorpropamidecholestyramine†cimetidineciprofloxacincisaprideclarithromycinclofibratecyclophosphamide†danazoldextrandextrothyroxinediazoxidediclofenacdicumaroldiflunisaldisulfiramdoxycyclineerythromycinesomeprazoleethacrynic acidezetimibefenofibratefenoprofenfluconazolefluorouracilfluoxetineflutamidefluvastatinfluvoxaminegefitinibgemifibrozilglucagonhalothaneheparinibuprofenifosfamideindomethacininfluenza virus vaccineitraconazoleketoprofenketorolaclansoprazolelepirudinlevamisolelevofloxacinlevothyroxineliothyroninelovastatinmefenamic acidmethimazole†methyldopamethylphenidatemethylsalicylate  ointment (topical)metronidazolemiconazole  (intravaginal, oral,    systemic)moricizine  hydrochloride†nalidixic acidnaproxenneomycinnorfloxacinofloxacinolsalazineomeprazoleoxandroloneoxaprozinoxymetholonepantoprazoleparoxetinepenicillin G,  intravenouspentoxifyllinephenylbutazonephenytoin†piperacillinpiroxicampravastatin†prednisone†propafenonepropoxyphenepropranololpropylthiouracil†quinidinequininerabeprazoleranitidine†rofecoxibsertralinesimvastatinstanozololstreptokinasesulfamethizolesulfamethoxazolesulfinpyrazonesulfisoxazolesulindactamoxifentetracyclinethyroidticarcillinticlopidinetissue plasminogen  activator (t-PA)tolbutamidetramadoltrimethoprim/  sulfamethoxazoleurokinasevaldecoxibvalproatevitamin Ewarfarin overdosezafirlukastzileuton
edemahereditary coumarin resistancehyperlipemiahypothyroidismnephrotic syndrome
Adrenal Cortical Steroid  InhibitorsAntacidsAntianxiety AgentsAntiarrhythmics†Antibiotics†Anticonvulsants†Antidepressants†AntihistaminesAntineoplastics†Antipsychotic MedicationsAntithyroid Drugs†BarbituratesDiuretics†Enteral Nutritional  SupplementsFungal Medications, Systemic†Gastric Acidity and Peptic  Ulcer Agents†Hypnotics†Hypolipidemics†  Bile Acid-Binding Resins†  HMG-CoA Reductase Inhibitors†ImmunosuppressivesOral Contraceptives, Estrogen  ContainingSelective Estrogen Receptor  ModulatorsSteroids, Adrenocortical†Tuberculosis Agents†Vitamins†
also: diet high in vitamin K        unreliable PT/INR determinations†Increased and decreased PT/INR responses have been reported.
alcohol†aminoglutethimideamobarbitalatorvastatin†azathioprinebutabarbitalbutalbitalcarbamazepinechloral hydrate†chlordiazepoxidechlorthalidonecholestyramine†clozapinecorticotropincortisonecyclophosphamide†dicloxacillinethchlorvynolglutethimidegriseofulvinhaloperidolmeprobamate6-mercaptopurinemethimazole†moricizine hydrochloride†nafcillinparaldehydepentobarbitalphenobarbitalphenytoin†pravastatin†prednisone†primidonepropylthiouracil†raloxifeneranitidine†rifampinsecobarbitalspironolactonesucralfatetrazodonevitamin C (high dose)vitamin Kwarfarin underdosage


Botanical (Herbal) Medicines





      Caution should be exercised when botanical medicines (botanicals) are taken concomitantly with warfarin. Few adequate, well-controlled studies exist evaluating the potential for metabolic and/or pharmacologic interactions between botanicals and warfarin. Due to a lack of manufacturing standardization with botanical medicinal preparations, the amount of active ingredients may vary. This could further confound the ability to assess potential interactions and effects on anticoagulation. It is good practice to monitor the patient's response with additional PT/INR determinations when initiating or discontinuing botanicals.

      Specific botanicals reported to affect warfarin therapy include the following:

      Some botanicals may cause bleeding events when taken alone (e.g., garlic and Ginkgo biloba) and may have anticoagulant, antiplatelet, and/or fibrinolytic properties. These effects would be expected to be additive to the anticoagulant effects of warfarin. Conversely, other botanicals may have coagulant properties when taken alone or may decrease the effects of warfarin.

      Some botanicals that may affect coagulation are listed below for reference; however, this list should not be considered all-inclusive. Many botanicals have several common names and scientific names. The most widely recognized common botanical names are listed.

      Botanicals that contain coumarins with potential anticoagulant effects:
      Agrimony AlfalfaAngelica (Dong Quai)AniseedArnicaAsafoetidaBogbean BoldoBuchuCapsicum Cassia CeleryChamomile (German and Roman)Dandelion FenugreekHorse ChestnutHorseradishLicorice Meadowsweet NettleParsleyPassion FlowerPrickly Ash (Northern)QuassiaRed CloverSweet CloverSweet WoodruffTonka BeansWild CarrotWild Lettuce
         
      Miscellaneous botanicals with anticoagulant properties:
      Bladder Wrack Pau d'arco
         
      Botanicals that contain salicylate and/or have antiplatelet properties:
      Agrimony Aloe GelAspenBlack CohoshBlack HawBogbean Cassia CloveDandelion FeverfewGarlic German SarsaparillaGingerGinkgo BilobaGinseng Licorice Meadowsweet Onion PolicosanolPoplarSenegaTamarindWillowWintergreen
         
      Botanicals with fibrinolytic properties:
      BromelainsCapsicum Garlic Ginseng Inositol NicotinateOnion
         
      Botanicals with coagulant properties:
      Agrimony Mistletoe
      GoldensealYarrow


      Effect on Other Drugs

      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.

      Considerations for Increased Bleeding Risk

      Warfarin sodium is a narrow therapeutic range (index) drug, and additional caution should be observed when warfarin sodium is administered to certain patients. Reported 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. Identification of risk factors for bleeding and certain genetic variation in CYP2CP and VKORC1 in a patient may increase the need for more frequent INR monitoring and the use of lower warfarin doses (see and ). Bleeding is more likely to occur during the starting period and with a higher dose of warfarin sodium (resulting in a higher INR).

      Intramuscular (I.M.) 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 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/INR, 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 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

      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 ).

      Use in Pregnancy

      Pregnancy Category X - See

      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 ).


      What are the side effects of Warfarin Sodium?

      Potential adverse reactions to warfarin may include:

      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.

      • 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 )
      • 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 .)
      • 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.



      What should I look out for while using Warfarin Sodium?

      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:

      The most serious risks associated with anticoagulant therapy with warfarin sodium are hemorrhage in any tissue or organ (see ) and, less frequently (
      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.

      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.

      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:

      Lactation:

      Severe to moderate hepatic or renal insufficiency.

      Infectious diseases or disturbances of intestinal fora:

      Trauma

      Surgery or trauma

      Indwelling catheters.

      Severe to moderate hypertension.

      Known or suspected deficiency in protein C mediated anticoagulant response:

      Miscellaneous:


      What might happen if I take too much Warfarin Sodium?


      How should I store and handle Warfarin Sodium?

      Sorry No Records found


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      Clinical Information

      Chemical Structure

      No Image found
      Clinical Pharmacology

      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.

      Non-Clinical Toxicology
      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:

      The most serious risks associated with anticoagulant therapy with warfarin sodium are hemorrhage in any tissue or organ (see ) and, less frequently (
      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.

      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.

      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:

      Lactation:

      Severe to moderate hepatic or renal insufficiency.

      Infectious diseases or disturbances of intestinal fora:

      Trauma

      Surgery or trauma

      Indwelling catheters.

      Severe to moderate hypertension.

      Known or suspected deficiency in protein C mediated anticoagulant response:

      Miscellaneous:

      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:

      EXOGENOUS FACTORS:

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

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

      ENDOGENOUS FACTORS:

      EXOGENOUS FACTORS:

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

      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.

      Periodic determination of PT/INR is essential. (see

      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.

      Potential adverse reactions to warfarin may include:

      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.

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      Reference

      This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
      "https://dailymed.nlm.nih.gov/dailymed/"

      While we update our database periodically, we cannot guarantee it is always updated to the latest version.

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      Professional

      Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72
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      Interactions

      Interactions

      A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).