fbpx

Warfarin

This post is under review 25/07/24

CLASS

  • anticoagulant

INDICATIONS

  • Venous or arterial thromboembolism prophylaxis or treatment
  • Thrombophilia: e.g. Factor V Leiden, Anti-phospholipid Syndrome
  • Atrial Fibrillation
  • Valve replacements

MECHANISM OF ACTION

  • Inhibits
  • prevents the synthesis of vitamin K dependent clotting factors
  • II, VII, IX & X in liver
  • prevents the reduction of vitamin K 2, 3-epoxide -> vitamin K

PHARMACEUTICS

  • tablets: 0.5, 1, 3 & 5mg
  • racemic mixture of warfarin sodium
  • **Important note** Marevan and Coumadin ARE NOT interchangeable

DOSE

  • 0.2mg/kg to load with in paediatrics
  • load with 5, 5, 5mg
  • maximum effect at 24-72hrs

INR Targets

  • DVT and PE: 2.0-3.0
  • Atrial fibrillation: 2.0-3.0
  • Bioprosthetic heart valves: 2.0-3.0
  • Mechanical heart valves: 2.5-3.5

ADVERSE EFFECTS

  • procoagulant effect with initiation of treatment (due to protein C and S depletion)
  • bleeding
  • teratogenic in pregnancy
  • Hypersensitivity

INTERACTIONS
Increase INR: Liver enzyme inhibition, Highly protein bound drugs (e.g. NSAIDs)
Decrease INR: Liver enzyme induction

PHARMACOKINETICS

  • Absorption – 100% bioavailable, Onset: 8-12 hours after loading dose
    Peak effect up to 72 hours (reflecting T1/2B of previously formed clotting factors
  • Distribution – 99% protein bound, Vd = 0.15L/kg
  • Metabolism – hepatic
  • Elimination – Predominantly urine, some faecal, t½B = 40 hrs

REVERSAL

  • Conservative: Waiting for new factors to be formed
  • Vitamin K administration
  • Fresh Frozen Plasma (FFP)
  • Prothrombinex

PATIENT EDUCATION

Patients on warfarin therapy should have the following explained:

  • Reason for treatment
  • Mechanism of action of warfarin
  • Time of day to take warfarin (same time of day)
  • The INR, target range and need for regular testing
  • Signs and symptoms of bleeding
  • Effect of illness, injury or any changes in physical status
  • Potential effect of invasive procedure, surgery or dental work
  • The effects of common over-the-counter (OTC) medication interactions
  • The need for consistent intake of vitamin K-rich foods
  • Effects of alcohol intake
  • Appropriate action if diarrhoea or vomiting occurs

CCC Pharmacology Series

Critical Care

Compendium

Dr James Pearlman LITFL Author

ICU Advanced Trainee BMedSci [UoN], BMed [UoN], MMed(CritCare) [USyd] from a broadacre farm who found himself in a quaternary metropolitan ICU. Always trying to make medical education more interesting and appropriately targeted; pre-hospital and retrieval curious; passionate about equitable access to healthcare; looking forward to a future life in regional Australia. Student of LITFL.