Warfarin
also: vitamin K antagonist · coumarin
Overview
Vitamin K antagonist still required where DOACs are contraindicated — mechanical valves and significant mitral stenosis. INR-monitored.
Mechanism
Inhibits vitamin-K epoxide reductase (VKORC1) → ↓regeneration of reduced vitamin K → ↓γ-carboxylation of clotting factors II, VII, IX, X and proteins C & S. Delayed onset (existing factors must degrade); initial transient procoagulant state (protein C falls first) → cover with heparin/LMWH when starting for VTE.
Indications
- Mechanical heart valves (DOACs contraindicated)
- Significant mitral stenosis with AF
- VTE / AF where DOAC unsuitable
- Antiphospholipid syndrome
Adverse effects
Reverse per severity: vitamin K ± PCC (Beriplex) for major bleeding; FFP if PCC unavailable.
Early, protein-C related — cover with heparin at initiation.
Warfarin embryopathy — switch to LMWH in pregnancy.
Cautions & contraindications
Embryopathy; use LMWH.
Interactions
- CYP inducers (rifampicin, carbamazepine, St John's wort) → ↓INR
- CYP inhibitors (clarithromycin, fluconazole, amiodarone, metronidazole) → ↑INR/bleeding
- Cranberry/grapefruit juice
- Alcohol (acute vs chronic differ)
- Antiplatelets/NSAIDs ↑bleeding
Monitoring & kinetics
INR (target 2–3 most indications; 3–4 / 2.5–3.5 for mechanical valves),Reverse: vitamin K (slow), PCC (fast, for major bleeding)
Narrow therapeutic index; many food/drug interactions; effect delayed 48–72 h.
Choosing it
true
Source: BNF — Warfarin