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 Essential 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