Warfarin

General

• Type: anticoagulant
• Dosage Forms: oral
• Common Trade Names: Coumadin

Adult Dosing

• Day 1: 5 - 7.5mg oral at bedtime (to ensure absorption on empty stomach)
• Day 2 and beyond: 2.5 - 7.5mg daily (usually 5mg)
• INR increase of >0.3 - 0.4 per day requires dose reduction
• Response also influenced by congestive heart failure, liver disease, Vitamin K deficiency, many drugs

Target Range of INR

• 2.5 - 3.5: Mechanical prosthetic valves or recurrent thromboembolism
• 2.0 - 3.0: All other indications

Pediatric Dosing

Safety and efficacy not well-established, though it is sometimes used in pediatrics for VTE treatment

Special Populations

• Pregnancy Rating: Contraindicated (Category D)
• Lactation risk: infant risk minimal
• Renal Dosing: caution advised
• Hepatic Dosing: consider decreased dose

Contraindications

• Allergy to class/drug
• Active bleeding or tendency to bleed

Adverse Reactions

• Bleeding
  • Risk increased when INR >3
  • Exponential increase when INR >5
  • Avoid giving NSAIDs, sulfas, macrolidies (azithromycin ok), fluoroquinolones
• Skin necrosis
  • Usually in patient with protein C deficiency
  • Occurs 3 - 8 days after starting treatment
• Treatment: see Warfarin (Coumadin) Reversal

Pharmacology

• Half-life: 20-60h (anticoagulant effect)
  • Of note, half-life highly variable based on rate of clotting factor catabolism
• Metabolism: Liver
• Excretion: Urine 92%, bile
• Mechanism of Action:
  • Blocks activation of vitamin K dependent prothrombotic factors II, VII, IX, X
  • Blocks synthesis of vitamin K dependent antithrombotic proteins C and S
• Albumin bound

Comments

• Because of differing factor half-lives, can cause transient (24-36 hour) prothrombosis at start of therapy
  • Bridge with heparin for 1-2 days until INR is in desired range

See Also

• Warfarin (Coumadin) Reversal
• Coagulopathy (Main)