Unifarin

N/A

Warfarin is indicated in the following conditions- Prophylaxis and/or treatment of thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement Indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction ... Read moreWarfarin is indicated in the following conditions- Prophylaxis and/or treatment of thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement Indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction Prophylaxis and treatment of venous thrombosis and pulmonary embolism Transient ischaemic attacks.

N/A

Warfarin can not be administered in the following cases; Actual or potential hemorrhagic conditions, eg. Peptic ulcer, or to patients with uncontrolled hypertension Severe hepatic or renal disease Pregnancy Known hypersensitivity to warfarin Bacterial endocarditis Its use within 24 hours following surgery or labor should be undertaken with caution, if at all.

Warfarin is a [vitamin K] antagonist which acts to inhibit the production of vitamin K by vitamin K epoxide reductase. The reduced form of vitamin K, vitamin KH2 is a cofactor used in the γ-carboxylation of coagulation factors VII, IX, X, and thrombin. Carboxylation induces a conformational change allowing the factors to bind Ca2+ and to phospholipid surfaces. Uncarboxylated factors VII, IX, X, and thrombin are biologically inactive and therefore serve to interrupt the coagulation cascade. The endogenous anticoagulation proteins C and S also require γ-carboxylation to function. This is particularly true in the case of thrombin which must be activated in order to form a thrombus. vitamin KH2 is converted to vitamin K epoxide as part of the γ-carboxylation reaction catalyzed by γ-glutamyl carboxylase. Vitamin K epoxide is then converted to vitamin K1 by vitamin K epoxide reductase then back to vitamin KH2 by vitamin K reductase. Warfarin binds to vitamin K epoxide reductase complex subunit 1 and irreversibly inhibits the enzyme thereby stopping the recycling of vitamin K by preventing the conversion of vitamin K epoxide to vitamin K1. This process creates a hypercoagulable state for a short time as proteins C and S degrade first with half lives of 8 and 24 hours, with the exception of factor VII which has a half life of 6 hours. Factors IX, X, and finally thrombin degrade later with half lives of 24, 36, and 50 hours resulting in a dominant anticoagulation effect. In order to reverse this anticoagulation vitamin K must be supplied, either exogenously or by removal of the vitamin K epoxide reductase inhibition, and time allowed for new coagulation factors to be synthesized. It takes approximately 2 days for new coagulation factors to be synthesized in the liver. Vitamin K2, functionally identical to vitamin K1, is synthesized by gut bacteria leading to interactions with antibiotics as elimination of these bacteria can reduce vitamin K2

Oral anticoagulants have a greater potential for clinically significant drug interactions. Warn all patients about potential hazards and instruct against taking or withdrawing any drug, including non-prescription products, without the advice of a physician.

Hemorrhage is the principal adverse effect of oral anticoagulants. Other adverse reactions include nausea, vomiting, diarrhea, hypersensitivity, rash, alopecia, and unexplained drop in haematocrit, "purple toes", skin necrosis, jaundice, and hepatic dysfunction.

If hemorrhage occurs or a potential bleeding state arises, excessive depression of the coagulation activity can be corrected by temporary withdrawal of warfarin accompanied, if necessary, by infusion of fresh-frozen plasma or whole blood. Vitamin K, 5 mg to 10 mg orally or intravenously, may be required to supplement specific treatment with co-factor concentrates.

Warfarin is contraindicated in the first trimester of pregnancy because of the risk of teratogenicity. It should not be used in women who are or may become pregnant because the drug passes through the placental barrier and may cause fatal hemorrhage to the fetus. Warfarin appears in the milk of nursing mothers in an inactive form. Infants nursed by mothers treated with Warfarin had no change in prothrombin times. Effects in premature infants have not been evaluated.

Periodic determination of prothrombin time (PT)/international normalized ratio (INR) or other suitable coagulation test is essential. Numerous factors, alone or in combination, including travel, changes in diet, environment, physical state and medication may influence response of the patient to anticoagulants. It is generally good practice to monitor the patient's response with additional PT/INR determination in the period immediately after discharge from the hospital, and whenever other medications are initiated, discontinued or taken irregularly. The following factors may exaggerate the effects of warfarin and necessitate a reduction in dosage; loss of weight, elderly subject, acute illness, deficient renal function, decreased dietary intake of vitamin K, administration of certain drugs (see drug interaction). Factors which may call for an increase in maintenance dosage include weight gain, diarrhea and vomiting, increased intake of vitamin K, fats and oils, and the administration of certain drugs. Careful additional laboratory control is necessary if the patient is to be changed from one formulation to another. Reversal of warfarin anticoagulation by vitamin K takes several days. In emergency situations fresh frozen plasma should be given.