Warfarin
Warfarin is an oral vitamin K antagonist used in adults for the prevention and treatment of venous thromboembolism, atrial fibrillation thromboembolism and selected mechanical heart valves. It requires periodic INR monitoring and dose adjustment.
- Chemical formula
- C19H16O4
- CAS number
- 81-81-2
- ATC code
- B01AA03
- Molecular weight
- 308.33 g/mol
- Drug class
- Vitamin K antagonist (oral anticoagulant)
- Also known as
- WARF-42, Warfarina
What is it?
Warfarin is a coumarin-type oral anticoagulant first introduced as a rodenticide in the 1940s and approved for human use in the 1950s. It is supplied as oral tablets at multiple strengths and is dispensed only on prescription. Warfarin appears on the World Health Organization List of Essential Medicines. Despite the introduction of direct oral anticoagulants, warfarin remains essential in selected indications such as mechanical heart valves and severe renal impairment.
Mechanism of action
Warfarin inhibits vitamin K epoxide reductase complex 1 (VKORC1), the enzyme responsible for regenerating reduced vitamin K, a cofactor for the gamma-carboxylation of clotting factors II, VII, IX and X and proteins C and S. The result is the synthesis of partially functional clotting factors with reduced procoagulant activity. The clinical onset is delayed because circulating active factors must be cleared before the anticoagulant effect is fully established.
Pharmacokinetics
Warfarin is rapidly and almost completely absorbed orally, with peak plasma concentrations reached after one to four hours. It is highly bound to plasma albumin (over 99%). The drug is a racemic mixture; the more potent S-enantiomer is metabolised mainly by CYP2C9, while the R-enantiomer is metabolised by CYP1A2 and CYP3A4. The terminal half-life is approximately 36 to 42 hours. Genetic variants of CYP2C9 and VKORC1 substantially influence dose requirements.
Indications
Warfarin is approved in adults for the prevention and treatment of venous thromboembolism, including deep vein thrombosis and pulmonary embolism, for the prevention of thromboembolic events in atrial fibrillation, for selected mechanical heart valves and after some cardiac procedures. According to international guidelines, direct oral anticoagulants are now preferred in non-valvular atrial fibrillation in many patients, but warfarin retains a defined role in valvular and severe renal disease.
Safety profile
The main adverse effect is bleeding, ranging from minor bruising to severe gastrointestinal or intracranial haemorrhage. Skin necrosis and the rare 'purple toe' syndrome have been reported, particularly during initiation. Warfarin has many drug and food interactions, especially through CYP2C9 and via vitamin K intake from green vegetables. According to the prescribing information, the international normalised ratio (INR) must be monitored regularly to maintain anticoagulation within the therapeutic range and minimise complications.
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Frequently asked questions
Why does warfarin require INR monitoring? ▾
Warfarin has a narrow therapeutic window and high inter-individual variability in dose requirements due to genetics, diet, comorbidity and concomitant medications. The international normalised ratio (INR) is used to keep anticoagulation within a defined therapeutic range, typically 2 to 3 in atrial fibrillation. According to the prescribing information, regular monitoring and dose adjustment by a qualified clinician are essential to limit the risk of bleeding and thrombosis.
Should green vegetables be avoided with warfarin? ▾
Vitamin K, abundant in green leafy vegetables, antagonises warfarin's effect, and a sudden change in vitamin K intake can destabilise the INR. According to international guidelines, patients on warfarin should aim for a consistent vitamin K intake rather than complete avoidance. Significant changes in diet, including starting or stopping a green-vegetable-rich plan, should be discussed with the prescriber and accompanied by INR re-checks.
How is warfarin different from direct oral anticoagulants? ▾
Warfarin acts indirectly by reducing the synthesis of multiple clotting factors and requires regular INR monitoring. Direct oral anticoagulants (DOACs) inhibit a single clotting factor (Xa or thrombin) without routine monitoring and have fewer dietary interactions. According to international guidelines, DOACs are preferred in non-valvular atrial fibrillation for many patients, while warfarin remains essential for mechanical valves and in some severe renal impairment scenarios.
What should be done in case of bleeding while on warfarin? ▾
Minor bleeding such as epistaxis or small bruises rarely requires immediate intervention but should be reported to the prescriber. Major bleeding requires urgent medical assessment; depending on severity and INR, treatment may include vitamin K, fresh frozen plasma or prothrombin complex concentrate. According to international guidelines, all patients on warfarin should be given written information on bleeding signs and emergency contacts.
What are the main contraindications for warfarin? ▾
Warfarin is contraindicated in known hypersensitivity, in active major bleeding, in severe uncontrolled hypertension, in haemorrhagic stroke without resolution, in advanced kidney or liver failure with coagulopathy, and during pregnancy except in selected mechanical valve scenarios. Caution is required in falls risk, alcohol misuse and uncertain compliance with monitoring. According to the prescribing information, the medical history must be reviewed by a clinician before any prescription.
The information on this website is provided for reference and educational purposes only. It does not replace consultation with a qualified healthcare professional.