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Warfarin

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warfarin (WOR-fuh-rin)A drug that prevents blood from clotting. It belongs to the family of drugs called anticoagulants (blood thinners). Warfarin is a commonly used oral anticoagulant with anti-vitamin K activity. 

Warfarin tablets, 5, 3 and 1mg
Warfarin tablets, 5, 3 and 1mg
Warfarin
Warfarin

Liver safety of Warfarin

Warfarin therapy is associated with rare instances of idiosyncratic, clinically apparent liver injury that are usually mild and rapidly reversible on stopping.

Mechanism of action of Warfarin

Warfarin (war' far in) was discovered after identification of the hemorrhagic activity that caused toxicity and bleeding in cattle after eating spoiled, sweet clover silage. 

As rodenticide

Once the active component was shown to be bis-hydroxycoumarin, synthetic derivatives were developed and found to be effective rodenticides.  Only thereafter were coumarin derivatives shown to be useful as Anticoagulants in humans, and only with careful monitoring.  Importantly, coumarin itself does not have anticoagulant activity but is used as an antineoplastic agent, and has different effects and side effects than its derivatives. 

Coumarin derivatives

Coumarin derivatives include warfarin, dicumarol, phenprocoumon and acenocoumarol. 

Mechanism of action of Warfarin

These compounds act by blocking the enzymatic reduction of vitamin K to its active form, which is responsible for the final steps of synthesis of several clotting factors (Factors II, VII, IX and X). 

Indications

Right leg affected by warfarin necrosis
Right leg affected by warfarin necrosis

The coumarin derivatives cause a prolongation of the prothrombin time which is beneficial in preventing progression or recurrence of deep vein thrombosis and pulmonary embolism.  Oral anticoagulation is also used to prevent arterial or venous embolization after acute myocardial infarction, atrial fibrillation and prosthetic heart value placement. 

FDA approval information for Warfarin

Warfarin, a first generation coumarin anticoagulant.
Warfarin, a first generation coumarin anticoagulant.

Warfarin was approved for use in the United States in 1961 and remains in wide use with more than 30 million prescriptions filled yearly.  The typical dose is 5 mg daily for 2 to 4 days followed by 2 to 10 mg daily, based upon measurements of prothrombin time aiming at an international normalized ratio (INR) value of 2 to 3.  Monitoring of the INR is essential during warfarin therapy, because bleeding is a common side effect and can be life-threatening and fatal. 

Side effects of Warfarin

Side effects not directly attributable to the anticoagulant activity of warfarin are not common, but can include nausea, abdominal discomfort, diarrhea, anorexia, fever, alopecia, skin necrosis and bluish discoloration.  Finally, warfarin is very sensitive to drug-drug interactions involving its metabolism or function and great care must be given to starting or stopping concurrent medications in patients on warfarin therapy.  Severe bleeding episodes can be caused by administration of another medication that prolongs its half-life or activity.

Warfarin resistance

Some people develop tolerance to warfarin called warfarin resistance, either partial or complete, that hinders their ability to use warfarin.

Brand names

US brand names include Coumadin®, Jantoven®

Overdose

Symptoms of overdose may include the following:

  • bloody or red, or tarry bowel movements
  • spitting or coughing up blood
  • heavy bleeding with your menstrual period
  • pink, red, or dark brown urine
  • coughing up or vomiting material that looks like coffee grounds
  • small, flat, round red spots under the skin
  • unusual bruising or bleeding
  • continued oozing or bleeding from minor cuts

Latest research

PubMed
  1. Therapeutic warfarin use and the extrahepatic functions of vitamin K-dependent proteins.

Donaldson CJ, Harrington DJ.Br J Biomed Sci. 2017 Oct;74(4):163-169. doi: 10.1080/09674845.2017.1336854. Epub 2017 Jun 28. Whilst some studies do link warfarin use to an increase in osteoporosis and fracture risk others have not. Learn more.

  1. Interactions of warfarin with drugs and food.

Wells PS, Holbrook AM, Crowther NR, Hirsh J. Ann Intern Med. 1994 Nov 1;121(9):676-83. doi: 10.7326/0003-4819-121-9-199411010-00009.

Of 86 different drugs and foods appraised, 43 had level 1 evidence. Of these, 26 drugs and foods did interact with 'warfarinWarfarin''s anticoagulant effect was potentiated by 6 antibiotics (cotrimoxazole, erythromycin, fluconazole, isoniazid, metronidazole, learn more...

  1. Systematic overview of warfarin and its drug and food interactions.

Inter-rater agreement was excellent, with weighted kappa values of 0.84 to 1.00. Of all reports, 72% described a potentiation of 'warfarin''s effect and 84% were of poor quality, 86% of which were single case reports. Learn more...

  1. Clinical pharmacokinetics and pharmacodynamics of warfarin. Understanding the dose-effect relationship.

Clin Pharmacokinet. 1986 Nov-Dec;11(6):483-504. doi: 10.2165/00003088-198611060-00005.

Prothrombin complex synthesis is inhibited 50% at a warfarin concentration of about 1.5 mg/L. Warfarin concentrations associated with therapeutic anticoagulation are of similar magnitude. ...On average it will take 3 days for the anticoagulant effect of warfarin. Learn more

  1. Review on mechanisms and interactions in concomitant use of herbs and warfarin therapy.

The effectiveness of warfarin, an oral anticoagulant originally derived from a plant, is strongly affected by patient's characteristics such as the age, presence of comorbidities, and concomitant use of another drug. Learn more...

Cost and Coupons - Warfarin

Reviews for Warfarin

Learn more about Warfarin

Latest research (Pubmed)

PubMed
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