Warfarin

Vitamin K antagonist - vitamin K dependent clotting factors: II, VII, IX, X and protein C and S

Indications:

• Mechanical heart valves
• Valvular atrial fibrillation
• End-stage renal failure needing anticoagulation

Contraindications

• Malignancy
• Bleeding
• Pregnancy
• 72 hours before major surgery, 48 hours postpartum
• Severe hypertension

INR Targets

INR 2-3 - for VTE, AF, valvular disease

INR 2.5-3.5 - for mechanical heart valves

• Higher targets may be required if there is recurrence
• Treatment duration is lifelong except for management of VTE (3 months if resolved 6+ if not)
• May take 5 days to achieve INR to therapeutic range
• Warfarin can induce a hypercoagulable state because the suppression of protein C occurs much quicker than the coagulation factors
  • If a patient develops an acute VTE and is at high risk of another heparin should be considered for 5 days

Interactions

Cytochrome P450 - extensive list of drug interactions 

• Enzyme inducers decrease the amount of active warfarin and decrease its efficacy (and INR). St John's wort, phenytoin and carbamazepine
• Enzyme inhibitors increase the amount of active warfarin in the body and increase potency (increase INR). Amiodarone, metronidazole, clarithromycin
• Many antibiotics also interact
• Consuming foods with an excess of vitamin K may reduce warfarins efficacy - constant diet needed
• Cranberries and cranberry juice are an enzyme inhibitor for warfarin

Elimination

After rapid absorption warfarin is bound to plasma albumin with a 37 hr ½ life. It’s then metabolised in liver to give inactive metabolites excreted in urine and faeces