Anticoagulants · Hematology
Warfarin
Coumadin®(brand names vary by market)
The vitamin K antagonist: ancient, cheap, measurable, and demanding.
Mechanism
Inhibits vitamin K epoxide reductase (VKORC1), starving factors II, VII, IX, X (and proteins C and S) of their activation step. Effect lags days behind the dose because existing factors must decay.
Open the interactive pathwayIndications
- Mechanical heart valves
- Atrial fibrillation when DOACs are unsuitable
- Venous thromboembolism (selected)
- Antiphospholipid syndrome
Formulations
Dosing concepts
INR-guided
Dose is whatever keeps the INR in range (commonly 2-3); there is no standard dose, only a standard target.
Bridging
Protein C falls before the clotting factors, so initiation in thrombosis is covered with a parenteral anticoagulant.
Concepts, not prescribing instructions. Practice numbers live in current references and local protocols.
Pharmacokinetics
- Bioavailability
- ~100%
- Half-life
- 20-60 h (R and S enantiomers differ)
- Elimination
- hepatic: S-warfarin (the potent enantiomer) via CYP2C9. The axis of most PK interactions
- Protein binding
- ~99%
Adverse effects
- Bleedingcommon & serious
- Skin necrosis (early, protein C depletion)serious
- Teratogenicityserious
Contraindications & precautions
Contraindications
- Pregnancy (except mechanical valves in carefully selected cases)
- Active major bleeding
Precautions
- Every new or stopped medication
- Major dietary vitamin K shifts
- Falls risk
- Alcohol excess
Interactions
- Warfarin + NSAIDs (e.g. ibuprofen, naproxen)avoidMajor GI bleeding risk multiplies while the INR looks reassuring.
- Warfarin + Clarithromycin / erythromycincautionINR climbs within days of starting the antibiotic.
- Warfarin + Trimethoprim-sulfamethoxazoleavoidOne of the highest-risk warfarin combinations: INRs of 6+ and hospitalization-grade bleeding are well documented.
- Warfarin + Vitamin K-rich foods (leafy greens)monitorFluctuating intake makes the INR seesaw; a sudden salad enthusiasm drops it.
- Warfarin + AmiodaronecautionGradual INR rise over 2-6 weeks after amiodarone starts.
Monitoring
INR
The entire therapeutic contract · Frequent at initiation, spaced out when stable, and after ANY interacting change
Hemoglobin, signs of bleeding
The harm being balanced
Time in therapeutic range
Quality metric for the whole strategy
Counselling points
- Same time every day; if a dose is missed, never double up without advice.
- Keep vitamin K intake steady rather than avoiding greens entirely.
- Tell every prescriber and pharmacist you take warfarin. Antibiotics and painkillers commonly move the INR.
- Report black stools, unusual bruising, or bleeding that will not stop.
Clinical pearls
- Warfarin's interactions are the curriculum: 2C9 inhibitors raise INR slowly, gut-flora-suppressing antibiotics raise it fast, and NSAIDs bleed without moving the INR at all.
References & review
- Warfarin product monograph (consult the current version for your market) (monograph)
- Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed. (reference-work)
Last reviewed 2026-08-15 · jurisdiction: global · drug information changes; verify against current references before practice use.