Warfarin chemical structure3mg (blue), 5mg (pink) and 1mg (brown) warfarin tablets (UK colours)
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Coumadin

Warfarin (also known under the brand names of Coumadin® and Marevan®) is an anticoagulant medication that is administered orally. It is used for the prophylaxis of thrombosis and embolism in many disorders. Its activity has to be monitored by frequent blood testing for the international normalized ratio (INR). It is named for the Wisconsin Alumni Research Foundation. more...

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Warfarin was originally developed as a rat poison, and is still widely used as such, although warfarin-resistant rats are becoming more common.

Mechanism of action

Normally, vitamin K is converted to vitamin K epoxide in the liver. This epoxide is then reduced by the enzyme epoxide reductase. The reduced form of vitamin K epoxide is necessary for the synthesis of many coagulation factors (II, VII, IX and X, as well as protein C and protein S). Warfarin inhibits the enzyme epoxide reductase in the liver, thereby inhibiting coagulation.

Uses

Medical use

Warfarin is given to people with an excessive tendency for thrombosis. This can prevent growth or embolism (spread) of a thrombus. Common indications for warfarin use are atrial fibrillation, artificial heart valves, deep venous thrombosis and pulmonary embolism.

Therapeutic drug monitoring is required, as warfarin has a very narrow therapeutic index, which means the levels in the blood that are effective are close to the levels that cause bleeding. Dosing of warfarin is further complicated by the fact that it is known to interact with many other medications and other chemicals which may be present in appreciable quantities in food (including caffeine and ascorbic acid). These interactions range from enhancing warfarin's anticoagulation effect to reducing the effect of warfarin.

As a result, it is easy to over- or under-coagulate the patient. Warfarin's effects must be closely monitored: this is done by using the INR. Initially, checking may be as often as twice a week; the intervals can be lengthened if the patient manages stable therapeutic INR levels on a stable warfarin dose.

When initiating warfarin therapy ("warfarinisation"), the doctor will generally decide how strong the anticoagulant therapy needs to be. A common target INR level is 2.0-3.0, though it varies from case to case.

The new oral anticoagulant ximelagatran (Exanta®) does not require INR monitoring, and was expected to replace warfarin to a large degree when introduced; however, it has run into approval problems and as of 2005 it was not clear if or when it will ever become available for general use.

Pesticide use

Warfarin is used as a rodenticide for controlling rats and mice in residential, industrial, and agricultural areas. It is both odorless and tasteless. It is effective when mixed with food bait, because the rodents will return to the bait and continue to feed over a period of days, until a lethal dose is accumulated (considered to be 1 mg/Kg/day over four to five days). It may also be mixed with talc and used as a tracking powder, which accumulates on the animal's skin and fur, and is subsequently consumed during grooming. The use as rat poison is now declining because many rat populations have developed resistance to warfarin.

Read more at Wikipedia.org


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Low-dose coumadin
From Townsend Letter for Doctors and Patients, 8/1/04 by Jule Klotter

Coumadin (warfarin) is a blood thinner that doctors have used for 50 years to prevent blood clots in the legs of patients susceptible to venous thrombosis. Although it does prevent potentially fatal blood clots, the drug also leads to an increased risk of hemorrhagic stroke and other bleeding disorders if taken long-term. Consequently, doctors usually end full-dose coumadin treatment, which maintains an anticoagulant range of 2.0 to 3.0 [international normalized ratio (INR)], after 3 to 12 months. Once treatment ends, however, venous blood clots often recur.

Paul M. Ridker, MD, and colleagues decided to study the effectiveness of long-term, low-dose coumadin treatment. Low-dose coumadin maintains an anticoagulant range of 1.5 to 2.0 (INR). The four-year study followed 508 patients with a history of venous blood clots who had previously received full-dose coumadin for a median of 6 months. Half received low-dose coumadin, the rest were given a placebo. Their progress was monitored through office visits every two months. The researchers reviewed the data at least once a year. After the fourth review the researchers ended the study earlier than intended because the data showed that low-dose coumadin prevents venous blood clots without causing major bleeding episodes.

Results were released in February 24, 2003, and published in the New England Journal of Medicine (10 April 2003). Thirty-seven of the 253 patients receiving the placebo had recurrent venous blood clots, compared to only 14 of the 255 patients in the low-dose coumadin group. Women receiving coumadin showed an 80% reduction in risk of recurrent venous blood clots while men showed a 53% risk reduction. The risk of major hemorrhage in those on low-dose coumadin was very low. Only one confirmed stroke occurred among the low-dose coumadin group, compared to two in the placebo group. Overall, four people in the coumadin group and eight people in the placebo group died during the four-year study. Low-Dose Coumadin is Safe and Effective for Long-Term Prevention of Recurrent Venous Blood Clots. www.coloradohealthsite.org

Winslow, Ron. Blood Thinner at Low Dose Cuts Risks. The Wall Street Journal. 25 February 2003

COPYRIGHT 2004 The Townsend Letter Group
COPYRIGHT 2004 Gale Group

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