Generic Name : - warfarin (WAR far in) Dosage Form : - Tablets
Brand Names : - Coumadin, Jantoven

INTRODUCTION :    Warfarin is an anticoagulant (blood thinner). Warfarin reduces the formation of blood clots by blocking the formation of certain clotting factors. Warfarin is used to prevent heart attacks, strokes, and blood clots in veins and arteries. Warfarin may also be used for purposes other than those listed in this medication guide. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood. Instead, it acts on the liver to decrease the quantity of a few key proteins in blood that allow blood to clot. It was initially marketed as a pesticide against rats and mice and is still popular for this purpose, although more potent poisons such as brodifacoum have since been developed. A few years after its introduction, warfarin was found to be effective and relatively safe for preventing thrombosis and embolism (abnormal formation and migration of blood clots) in many disorders. It was approved for use as a medication in the early 1950s and has remained popular ever since; warfarin is the most widely prescribed oral anticoagulant drug in North America.


 IUPAC name :- (RS)-4-hydroxy- 3-(3- oxo- 1-phenylbutyl)- 2H- chromen- 2-one  Formula :C19H16O4  Mol. mass :308.33 g/mol  Melting point :- fffC Warfarin is a synthetic derivative of dicoumarol, a 4-hydroxycoumarin-derived mycotoxin anticoagulant. Dicoumarol, in turn, is derived from coumarin, a sweet-smelling but coagulationinactive chemical.

Excreted principally in urine as metabolites and to a lesser extent in bile Half-life : . Warfarin inhibits epoxide reductase[44] (specifically the VKORC1 subunit). within 24 hours).g. 1A2. 2C8. PIVKA-II). Elimination Route :. they are collectively referred to as PIVKAs (proteins induced [by] vitamin K absence/antagonism).MECHANISM OF ACTION : Warfarin inhibits the vitamin K-dependent synthesis of biologically active forms of the calciumdependent clotting factors II.Approximately 99%.Effective half-life averages 40 hours (range: 20–60 hours). As the body's stores of previously-produced active factors degrade (over several days) and are replaced by inactive factors.    . The end result of warfarin use. The enzyme that carries out the carboxylation of glutamic acid is gamma-glutamyl carboxylase. the drug has not been detected in human breast milk. is to diminish blood clotting in the patient. however. as well as the regulatory factors protein C. IX and X. Depletion of circulating functional coagulation factors must occur before therapeutic effects of the drug become apparent. protein S.The apparent volume of distribution is about 0. but have decreased functionality due to undercarboxylation. the anticoagulation effect becomes apparent. and protein Z. VII.  PHARMACOKINETICS :  Bioavailability :.2–5 days after a single dose. The precursors of these factors require carboxylation of their glutamic acid residues to allow the coagulation factors to bind to phospholipid surfaces inside blood vessels. which inhibits the carboxylation activity of the glutamyl carboxylase. and individual coagulation factors as PIVKA-number (e. Metabolism :.g.Almost entirely in the liver. the coagulation factors are no longer carboxylated at certain glutamic acid residues. thereby diminishing available vitamin K and vitamin K hydroquinone in the tissues.. When this occurs. but not extent. The coagulation factors are produced. and 3A4 involved to a lesser degree. Food :. Onset :. the vitamin K epoxide reductase (VKOR).    Distribution :. Principally by CYP2C9. The vitamin K epoxide is in turn recycled back to vitamin K and vitamin K hydroquinone by another enzyme.  Plasma Protein Binding :. Crosses the placental barrier. The carboxylation reaction will proceed only if the carboxylase enzyme is able to convert a reduced form of vitamin K (vitamin K hydroquinone) to vitamin K epoxide at the same time. on the vascular endothelium. Duration :. of absorption in the presence of food. and are incapable of binding to the endothelial surface of blood vessels.Decreased rate. therefore.Synthesis of vitamin K-dependent coagulation factors is affected soon after absorption (e. CYP2C19.Essentially completely absorbed after oral administration. and are thus biologically inactive.14 L/kg. 2C18.

a IV Administration : . the incidence of birth defects in infants exposed to warfarin. warfarin use during pregnancy is commonly associated with spontaneous abortion. stillbirth. IM administration not recommended. and to reduce the risk of pulmonary embolism. Administer orally. When warfarin (or another 4-hydroxycoumarin derivative) is given during the first trimester— particularly between the sixth and ninth weeks of pregnancy—a constellation of birth defects known variously as fetal warfarin syndrome (FWS).   Coumarins (such as warfarin) are also teratogens.   DOSAGE AND ADMINISTRATION :          Coumadin may be taken with or without food. Protime results help doctors adjust medication dose to avoid excessive blood thinning and risk of bleeding. Coumadin is also used in preventing blood clot closure of coronary artery stents. Coumadin is also used in patients with atrial fibrillation and artificial heart valves to reduce the risk of strokes. Oral Administration : . warfarin embryopathy. Reconstitution : . Compatibility under Stability. that is.Inject slowly (over 1–2 minutes) into a peripheral vein. they cause birth defects.For solution and drug compatibility information. as it passes through the placental barrier and may cause bleeding in the fetus. or coumarin embryopathy can occur. and preterm birth. CONTRAINDICATIONS :Anticoagulation in pregnancy :Warfarin is contraindicated in pregnancy. It is also helpful in preventing blood clot formation in certain orthopedic surgeries such as knee or hip replacements. daily dose.7 mL of sterile water for injection to a final concentration of 2 mg/mL. . Since Coumadin is metabolized by the liver and excreted by the kidneys. Administer by IV injection when a coumarin derivative is indicated and oral therapy is not feasible.INDICATIONS AND USAGE : Coumadin is used in treating patients with blood clots in the lower extremities to prevent extension of the clot. neonatal death. dosages need to be lowered in patients with liver and kidney dysfunction. Frequent blood tests are performed to measure blood clotting time (protime) during Coumadin treatment. Rate of Administration :.Administer orally in a single. Patients with pulmonary embolism are treated with Coumadin to prevent further blood clot emboli.Reconstitute powder for injection with 2.

A few examples of such medications include Aspirin.The only common side effect of warfarin is hemorrhage (bleeding). cimetidine (Tagamet). or if you have any other allergies. risk of maternal hemorrhage and other complications is still increased. WARNINGS & PRECAUTIONS : Before taking warfarin. it should be given in the arm. With heparin. bleeding from nose or gums. aspirin. but heparins do not cross the placental barrier and therefore do not cause birth defects. or other nonsteroidal anti-inflammatory drugs. If you must have an injection into a muscle (for example. a flu shot). Before using this medication. tell your doctor or pharmacist your medical history. can affect the anticoagulant action of Coumadin. Usually. which can cause allergic reactions or other problems. . This medication may cause stomach bleeding. This way. tell your doctor or pharmacist if you are allergic to it. Birth defects and fetal bleeding have been reported. and a low molecular weight heparin such as enoxaparin is substituted. frequent falls/injuries. mental/mood disorders (including memory problems). This product may contain inactive ingredients. ibuprofen (Motrin). certain vitamins. PREGNANCY :.Coumadin should be avoided by pregnant women or women who may become pregnant. The risk may also be increased in elderly patients and in patients on hemodialysis. Daily use of alcohol while using this medicine will increase your risk for stomach bleeding and may also affect how this medication works. oxandrolone (Oxandrin). both prescription and nonprescription (OTC). acetaminophen (Tylenol and others). hemophilia). excessive bruising. Avoid getting injections into the muscles.     DRUG INTERACTIONS :   Many drugs. alcohol use. and antibiotics. it will be easier to check for bleeding and/or apply pressure bandages. Some medications can enhance the action of Coumadin and cause excessive blood thinning and lifethreatening bleeding. bleeding problems (such as bleeding of the stomach/intestines. liver disease. alcohol. warfarin is avoided in the first trimester. recent major injury/surgery. Limit or avoid alcoholic beverages. blood vessel disorders (such as aneurysms).  The risks of bleeding is increased when warfarin is combined with antiplatelet drugs such as clopidogrel. especially of: blood disorders (such as anemia. The risk of severe bleeding is small but and may cause hemoptysis (coughing up blood). bleeding in the brain). ADVERSE REACTIONS :-a) Hemorrhage :. or blood in urine or stool.It is important that all your doctors and dentists know that you take warfarin.

This condition is thought to result from small deposits of cholesterol breaking loose and flowing into the blood vessels in the skin of the feet. c) Osteoporosis :.b) Warfarin necrosis :. contact a poison control center or emergency room immediately. which occurs more frequently shortly after commencing treatment in patients with a deficiency of protein C. unusual/prolonged bleeding.After initial reports that warfarin could reduce bone mineral density. OVERDOSAGE :  If overdose is suspected. STORAGE :     Store at room temperature away from light and moisture. but it affects other parts of the feet as well. d) Purple toe syndrome :. several studies have demonstrated a link between warfarin use and osteoporosis-related fracture.  It is typically thought to affect the big toe. Do not store in the bathroom.A rare but serious complication resulting from treatment with warfarin is warfarin necrosis. Taro .tablet & I. Symptoms of overdose may include: bloody/black/tarry stools. Keep all medications away from children and pets. pink/dark urine. which causes a blueish purple color and may be painful. Sandoz. The occurrence of purple toe syndrome may require discontinuation of warfarin. Properly discard this product when it is expired or no longer needed.V injections PROTECT FROM LIGHT & Moisture :. including the bottom of the foot (plantar surface). Product information   FORM : .yes MANUFACTURERS :o o Bristol-Myers Squibb Barr. Do not flush medications down the toilet or pour them into a drain unless instructed to do so.Another rare complication that may occur early during warfarin treatment (usually within 3 to 8 weeks of commencement) is purple toe syndrome.

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