Warfarin is an anticoagulant drug used to prevent blood clots. It is a synthetic derivative of dicoumarol that was developed by the Wisconsin Alumni Research Foundation. Warfarin works by inhibiting vitamin K epoxide reductase and preventing the recycling of vitamin K, which is necessary for blood clotting. It exists as a white crystalline powder and is available in oral tablet forms of 1mg, 3mg, and 5mg doses. Warfarin is used to prevent embolisms in conditions like atrial fibrillation and after inserting prosthetic heart valves, but has contraindications like peptic ulcers and should be used cautiously in hepatic or renal impairment.

1. WARFARIN
Darya Osman Hussein
Nile College
May, 2014

2. BRIEF INTRODUCTION AND HISTORY
• Anticoagulant
• Used in prevention of thrombosis and thromboembolism
• Synthetic derivative of dicoumarol (a 4-hydroxycoumarin derived
mycotoxin anticoagulant)
• Name comes from acronym of organization that funded the
research and discovery of the drug (Wisconsin Alumni Research
Foundation – WARF and –arin to indicate its link with coumarin)

3. SYNTHESIS OF WARFARIN

4. MOLECULAR STRUCTURE
• A cyclic tautomer (left) and cyclic hemiketal
tautomer (right)

5. GENERAL PROPERTIES
• Appearance
• White or almost white crystalline powder
• Solubility
• Very soluble in water, freely soluble in ethanol, soluble in
acetone, very slightly soluble in methylene chloride
• Appearance and pH of Solution
• clear colourless solution with pH of 7.6 – 8.6

6. WARFARIN SODIUM & WARFARIN SODIUM
CLATHRATE

7. • Pure Warfarin Sodium or mixture, in form of clathrate (i.e. salt) , of
Warfarin Sodium and Propan-2-ol in molecular proportions2:1
• Clathrate salt should contain approximately 98 – 102% warfarin
sodium
• Assay method – Infrared absorption spectrophotometry

8. ASSAY PROCEDURE
• Dissolve 0.100 g in 0.01M NaOH and dilute to 100.0 mls with the
same solvent.
• Dilute 10.0 mls of solution to 100.0 ml with 0.01M NaOH (X2)
• Measure absorbance at absorption maximum of308nm
• Using specific absorbance of 431, calculate the percent content

9. IMPURITIES
• Three main impurities can be found:
• (5RS)-3-(2-hydroxyphenyl)-5-phenylcyclohex-2-enone
• 4-hydroxy-2H-1-benzopyran-2-one (4-hydroxycoumarin)
• (3E)-4-phenylbut-3-en-2-one (benzalacetone)

10. DOSAGE FORM
• Oral Tablet
• Available in 1mg, 3mg and 5mg doses
• Usually coloured to ease identification
• Can contain Warfarin Sodium or Warfarin
Sodium Clathrate
• Content % = 95 – 105% of stated amount

11. PHYSIOLOGICAL ACTION
• Warfarin decrease blood coagulation by inhibiting vitamin K epoxide
reductase, an enzyme that recycles oxidized vitamin K1 to its reduced
form after it has participated in the carboxylation of several blood
coagulation proteins, mainly prothrombin and factor VII
• Despite being labeled a vitamin K antagonist, warfarin does not
antagonize the action of vitamin K1
• Warfarin antagonizes vitamin K1 recycling, depleting active vitamin K1
and the pharmacologic action may always be reversed by fresh vitamin
K1

12. CONTRA-INDICATIONS
• Indications:
• Prophylaxis of embolization in rheumatic heart disease and atrial
fibrillation
• Prophylaxis after insertion of prosthetic heart valve
• Prophylaxis and treatment of venous thrombosis and pulmonary
embolism
• Transient ischemic attacks
• Contra-indications:
• Peptic ulcer

13. ADDITIONAL INFORMATION
• Hepatic impairment:
• Should be avoided in severe impairment
• Renal Impairment:
• Should be used with caution in mild to moderate impairment
and avoided in severe impairment
• Should be used with prophylactic vitamin K for the infant

14. PREGNANCY AND BREASTFEEDING
• Pregnancy:
• Teratogenic (should not be given in first trimester)
• Can cross placenta and causes congenital malformations,
placental fetal or neonatal haemorrhage
• Breastfeeding:
• Not present in significant amounts and appears safe