[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Vitamin K antagonists](https://durgical.com/en/pharmacology/classes/vitamin-k-antagonists/) › Warfarin

[Pharmacology](https://durgical.com/en/pharmacology/) · [Vitamin K antagonists](https://durgical.com/en/pharmacology/classes/vitamin-k-antagonists/)

# Warfarin

An oral anticoagulant that blocks vitamin K recycling, so the liver makes fewer working clotting factors. Followed with the INR blood test.

Updated 2026-11-01

- Class: [Vitamin K antagonists](https://durgical.com/en/pharmacology/classes/vitamin-k-antagonists/)
- Enzyme: Vitamin K epoxide reductase (VKORC1)
- ATC code: B01AA03
- WHO Model List of Essential Medicines

✂**Vitamin K epoxide reductase (VKORC1)**Warfarin

ⓘ The figure shows human VKOR with S-warfarin, one of the two mirror-image forms of warfarin.

**Target in 3D:** Vitamin K epoxide reductase (VKORC1). PDB structure 6WV3 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/6WV3) · Drag to rotate · pinch to zoom

## Mechanism of action

Warfarin inhibits VKORC1, the enzyme that recycles vitamin K. With less active vitamin K, the liver makes fewer functional factors II, VII, IX and X, and less protein C and protein S. Some effect appears within a day, and the peak comes after several days, as the working factors already in the blood are cleared.

- Warfarin blocks VKORC1: vitamin K is not recycled
- The liver makes fewer working factors II, VII, IX and X
- Over days, the old functional factors are cleared
- Less thrombin: the INR rises and clots form less easily

## Pharmacokinetics

**Absorption**
Essentially completely absorbed by mouth.

**Distribution**
Almost entirely bound to plasma proteins; it crosses the placenta.

**Metabolism**
In the liver; the S form mainly by CYP2C9, an enzyme that varies between people.

**Elimination**
Almost all by metabolism; the metabolites leave mostly in the urine.

**Half-life**
Long: the effective half-life is about 20 to 60 hours.

**Onset and duration**
Some effect within a day; the peak may take 3 to 4 days.

## Indications

- Prevention of stroke and embolism in atrial fibrillation. [Atrial fibrillation →](https://durgical.com/en/conditions/atrial-fibrillation/)
- Treatment and prevention of deep vein thrombosis. [Deep vein thrombosis →](https://durgical.com/en/conditions/deep-vein-thrombosis/)
- Treatment and prevention of pulmonary embolism. [Pulmonary embolism →](https://durgical.com/en/conditions/pulmonary-embolism/)
- Heart valve replacement, including mechanical valves (for example after surgery for rheumatic valve disease). [Rheumatic heart disease →](https://durgical.com/en/conditions/rheumatic-heart-disease/)

## Adverse effects

### Common

- Bleeding (gums, nose, bruising, urine, stool)
- Hair loss
- Gas, bloating and abdominal pain

### Serious (rare, important)

- Serious, sometimes fatal bleeding
- Skin and tissue necrosis within days of starting (linked to low protein C and S)
- Purple toe syndrome (cholesterol microemboli)

## Contraindications

- Pregnancy (it crosses the placenta), except case by case with mechanical heart valves
- Bleeding tendencies or active bleeding
- Recent or planned brain, eye or major traumatic surgery
- Patients who cannot be followed reliably

## Key interactions

**CYP2C9 inhibitors (amiodarone, fluconazole, metronidazole, trimethoprim-sulfamethoxazole)**
Raise the INR and the risk of bleeding.

**CYP2C9 inducers (rifampicin, carbamazepine, phenobarbital)**
Lower the INR and the protection against clots.

**Aspirin and other NSAIDs**
Add to bleeding risk.

**Vitamin K in food or supplements**
Changes in intake move the INR; a steady intake keeps it stable.

## What is monitored

- INR (prothrombin time): the regimen is adjusted according to it
- Signs of bleeding
- CYP2C9 and VKORC1 genotypes, when known, help choose the starting regimen

## Memory aid

Warfarin starves the liver of working vitamin K: the factors leave the factory unfinished, and the INR is the quality check.

## Test yourself

Think of the answer, then tap the question to see it.

## Why can warfarin cause skin necrosis in the first days?

Warfarin also lowers proteins C and S, natural anticoagulants; their deficiency is linked to tissue necrosis that can appear within days of starting.

## How is the effect of warfarin reversed?

Stopping it and giving vitamin K restores factor production; for life-threatening bleeding, prothrombin complex concentrate or fresh frozen plasma can be considered.

## Why do warfarin requirements vary so much from person to person?

Variants in the CYP2C9 and VKORC1 genes, plus diet (vitamin K), other drugs and illness.

## A patient on warfarin starts fluconazole. What happens to the INR?

It rises: fluconazole inhibits CYP2C9, which breaks down S-warfarin, so bleeding risk increases and the INR is followed more closely.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/warfarin/)

## Related drugs

- [Heparin](https://durgical.com/en/pharmacology/heparin/)
- [Rivaroxaban](https://durgical.com/en/pharmacology/rivaroxaban/)
- [Dabigatran](https://durgical.com/en/pharmacology/dabigatran/)

## Related conditions

- [Atrial fibrillation](https://durgical.com/en/conditions/atrial-fibrillation/)
- [Deep vein thrombosis](https://durgical.com/en/conditions/deep-vein-thrombosis/)
- [Pulmonary embolism](https://durgical.com/en/conditions/pulmonary-embolism/)
- [Rheumatic heart disease](https://durgical.com/en/conditions/rheumatic-heart-disease/)

[← Back to the class: Vitamin K antagonists](https://durgical.com/en/pharmacology/classes/vitamin-k-antagonists/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - WARFARIN SODIUM tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95) (DailyMed (U.S. National Library of Medicine), 2026); [Warfarin: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682277.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [Prothrombin Time Test and INR (PT/INR)](https://medlineplus.gov/lab-tests/prothrombin-time-test-and-inr-ptinr/) (MedlinePlus (U.S. National Library of Medicine), 2024); [6WV3: Human VKOR with warfarin](https://www.rcsb.org/structure/6WV3) (RCSB Protein Data Bank, 2020).

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Representative model, for educational purposes only.

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