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
  • Lactation risk: infant risk minimal
  • Renal Dosing: caution advised
    • Adult
    • Pediatric
  • Hepatic Dosing: consider decreased dose
    • Adult
    • Pediatric

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

References