An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Waran is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Waran is also used as a rodenticide. .

Waran - Pharmacology:

Waran inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.

Waran Interactions

Drugs may interact with COUMADIN through pharmacodynamic or pharmacokinetic mechanisms. Pharmacodynamic mechanisms for drug interactions with COUMADIN 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 COUMADIN 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


blood dyscrasias — diarrhea hyperthyroidism
see CONTRAINDICATIONS elevated temperature poor nutritional state
cancer hepatic disorders steatorrhea
collagen vascular disease infectious hepatitis vitamin K deficiency
congestive heart failure jaundice  


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

Classes of Drugs
5-lipoxygenase Inhibitor Antiparasitic/Antimicrobials HMG-CoA Reductase
Adrenergic Stimulants, Central Antiplatelet Drugs/Effects Inhibitors
Alcohol Abuse Reduction Antithyroid Drugs Leukotriene Receptor Antagonist
Preparations Beta-Adrenergic Blockers Monoamine Oxidase Inhibitors
Analgesics Cholelitholytic Agents Narcotics,prolonged
Anesthetics, Inhalation Diabetes Agents, Oral Nonsteroidal Anti-Inflammatory
Antiandrogen Diuretics Agents
Antiarrhythmics Fungal Medications, Intravaginal, Psychostimulants
Antibiotics Systemic Pyrazolones
Aminoglycosides (oral) Gastric Acidity and Peptic Salicylates
Cephalosporins, parenteral Ulcer Agents Selective Serotonin
Macrolides Gastrointestinal Reuptake Inhibitors
Miscellaneous Prokinetic Agents Steroids, Adrenocortical
Penicillins, intravenous, Ulcerative Colitis Agents Steroids, Anabolic (17-Alkyl
high dose Gout Treatment Agents Testosterone Derivatives)
Quinolones (fluoroquinolones) Hemorrheologic Agents Thrombolytics
Sulfonamides, long acting Hepatotoxic Drugs Thyroid Drugs
Tetracyclines Hyperglycemic Agents Tuberculosis Agents
Anticoagulants Hypertensive Emergency Agents Uricosuric Agents
Anticonvulsants Hypnotics Vaccines
Antidepressants Hypolipidemics Vitamins
Antimalarial Agents Bile Acid-Binding Resins  
Antineoplastics Fibric Acid Derivatives  
Specific Drugs Reported
acetaminophen fluconazole penicillin G,intravenous
alcohol fluorouracil pentoxifylline
allopurinol fluoxetine phenylbutazone
aminosalicylic acid flutamide phenytoin
amiodarone HCl fluvastatin piperacillin
aspirin fluvoxamine piroxicam
atorvastatin gemfibrozil pravastatin
azithromycin glucagon prednisone
capecitabine halothane propafenone
cefamandole heparin propoxyphene
cefazolin ibuprofen propranolol
cefoperazone ifosfamide propylthiouracil
cefotetan indomethacin quinidine
cefoxitin influenza virus vaccine quinine
ceftriaxone itraconazole ranitidine
celecoxib ketoprofen rofecoxib
cerivastatin ketorolac sertraline
chenodiol levamisole simvastatin
chloramphenicol levofloxacin stanozolol
chloral hydrate levothyroxine streptokinase
chlorpropamide liothyronine sulfamethizole
cholestyramine lovastatin sulfamethoxazole
cimetidine mefenamic acid sulfinpyrazone
ciprofloxacin methimazole sulfisoxazole
cisapride methyldopa sulindac
clarithromycin methylphenidate tamoxifen
clofibrate methylsalicylate ointment tetracycline
COUMADIN overdose (topical) thyroid
cyclophosphamide metronidazole ticarcillin
danazol miconazole ticlopidine
dextran (intravaginal,systemic) tissue plasminogen
dextrothyroxine moricizine hydrochloride activator (t-PA)
diazoxide nalidixic acid tolbutamide
diclofenac naproxen tramadol
dicumarol neomycin trimethoprim/sulfamethoxazole
diflunisal norfloxacin urokinase
disulfiram ofloxacin valproate
doxycycline olsalazine vitamin E
erythromycin omeprazole zafirlukast
ethacrynic acid oxaprozin zileuton
fenofibrate oxymetholone  
fenoprofen paroxetine  

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.

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


edema hypothyroidism
hereditary coumarin resistance nephrotic syndrome


Potential drug interactions with COUMADIN (Waran Sodium) are listed below by drug class and by specific drugs.

Classes of Drugs
Adrenal Cortical Steroid Inhibitors Antithyroid Drugs HMG-CoA Reductase Inhibitors
Antacids Barbiturates Immunosuppressives
Antianxiety Agents Diuretics Oral Contraceptives,
Antiarrhythmics Enteral Nutritional Supplements Estrogen Containing
Antibiotics Fungal Medications, Systemic Selective Estrogen Receptor
Anticonvulsants Gastric Acidity and Modulators
Antidepressants Peptic Ulcer Agents Steroids, Adrenocortical
Antihistamines Hypnotics Tuberculosis Agents
Antineoplastics Hypolipidemics Vitamins
Antipsychotic Medications Bile Acid-Binding Resins  
Specific Drugs Reported
alcohol COUMADIN underdosage phenytoin
aminoglutethimide cyclophosphamide pravastatin
amobarbital dicloxacillin prednisone
atorvastatin ethchlorvynol primidone
azathioprine glutethimide propylthiouracil
butabarbital griseofulvin raloxifene
butalbital haloperidol ranitidine
carbamazepine meprobamate rifampin
chloral hydrate 6-mercaptopurine secobarbital
chlordiazepoxide methimazole spironolactone
chlorthalidone moricizine hydrochloride sucralfate
cholestyramine nafcillin trazodone
clozapine paraldehyde vitamin C (high dose)
corticotropin pentobarbital vitamin K
cortisone phenobarbital  

also: diet high in vitamin K unreliable PT/INR determinations

Increased and decreased PT/INR responses have been reported.

Because a patient may be exposed to a combination of the above factors, the net effect of COUMADIN 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.

Botanical (Herbal) Medicines

Caution should be exercised when botanical medicines (botanicals) are taken concomitantly with COUMADIN. Few adequate, well-controlled studies exist evaluating the potential for metabolic and/or pharmacologic interactions between botanicals and COUMADIN. 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 COUMADIN therapy include the following:

• Bromelains, danshen, dong quai (Angelica sinensis), garlic, Ginkgo biloba, and ginseng are associated most often with an INCREASE in the effects of COUMADIN.

• Coenzyme Q10 (ubidecarenone) and St. John’s wort are associated most often with a DECREASE in the effects of COUMADIN.

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

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.

Botanticals that contain coumarins with potential anticoagulant effects:
Alfalfa Celery Parsley
Angelica (Dong Quai) Chamomile Passion Flower
Aniseed (German and Roman) Prickly Ash (Northern)
Arnica Dandelion3 Quassia
Asa Foetida Fenugreek Red Clover
Bogbean1 Horse Chestnut Sweet Clover
Boldo Horseradish Sweet Woodruff
Buchu Licorice3 Tonka Beans
Capsicum2 Meadowsweet1 Wild Carrot
Cassia3 Nettle Wild Lettuce
Miscellaneous botanticals with anticoagulant properties:
Bladder Wrack (Fucus) Pau d’arco  
Botanicals that contain salicylate and/or have antiplatelet properties:
Agrimony4 Dandelion3 Meadowsweet1
Aloe Gel Feverfew Onion5
Aspen Garlic5 Policosanol
Black Cohosh German Sarsaparilla Poplar
Black Haw Ginger Senega
Bogbean1 Ginkgo Biloba Tamarind
Cassia3 Ginseng (Panax)5 Willow
Clove Licorice3 Wintergreen
Botanticals with fibrinolytic properties:
Bromelains Garlic5 Inositol Nicotinate
Capsicum2 Ginseng (Panax)5 Onion5
Botanticals with coagulant properties:
Agrimony4 Mistletoe Yarrow
1 Contains coumarins and salicylate.
2 Contains coumarins and has fibrinolytic properties.
3 Contains coumarins and has antiplatelet properties.
4 Contains salicylate and has coagulant properties.
5 Has antiplatelet and fibrinolytic properties.

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.

Special Risk Patients

COUMADIN (Waran Sodium) is a narrow therapeutic range (index) drug, and caution should be observed when warfarin sodium is administered to certain patients such as the elderly or debilitated or when administered in any situation or physical condition where added risk of hemorrhage is present.

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 COUMADIN (or warfarin) is administered concomitantly with nonsteroidal antiinflammatory 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.

Acquired or inherited warfarin resistance should be suspected if large daily doses of COUMADIN are required to maintain a patient’s PT/INR within a normal therapeutic range.


Potential adverse reactions to COUMADIN 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.

• 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.

• Adverse reactions reported infrequently include: hypersensitivity/allergic reactions, systemic cholesterol microembolization, purple toes syndrome, hepatitis, cholestatic hepatic injury, jaundice, elevated liver enzymes, vasculitis, edema, fever, rash, dermatitis, including bullous eruptions, urticaria, abdominal pain including cramping, flatulence/bloating, fatigue, lethargy, malaise, asthenia, nausea, vomiting, diarrhea, pain, headache, dizziness, 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.


Waran 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:


COUMADIN is 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 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 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,a nd other central nervous system abnormalities have been reported in association with second and third trimester exposure. Although rare, teratogenic reports following in utero 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.

Hemorrhagic tendencies or blood dyscrasias.

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

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

Threatened abortion, eclampsia and preeclampsia.

Inadequate laboratory facilities.

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

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

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

Generic name, Overdose, Half Life Waran, Food Interactions, Chemical, etc..

Waran see also


Chemical structure:
O O O O H H H H H H H H H H H H H H H H C19H16O4 2D chemical structure C19H16O4 SVG | 2D structure Warfarin | 4-Hydroxy-3-[(1s)-3-Oxo-1-Phenylbutyl]-2h-Chromen-2-One | chemical names, chemical properties, classification C19H16O4