Products
In many countries, no drugs containing warfarin are approved, and the closely related phenprocoumon (Marcoumar) is mainly used. However, warfarin is commonly used in other countries, particularly the United States, and is commercially available in tablet form (Coumadin) and other forms. It was approved in the United States in 1954.
Structure and properties
Warfarin (C19H16O4, Mr = 308.3 g/mol) is a derivative of 4-hydroxycoumarin present in drugs as a racemate. The -enantiomer is pharmacologically more active. Warfarin is present in drugs as warfarin sodium, a white, odorless, photosensitive, hygroscopic, amorphous powder that is very soluble in water.
Effects
Warfarin (ATC B01AA03) has anticoagulant properties. It inhibits the formation of blood clotting factors, the synthesis of which is dependent on vitamin K. The effects are based on inhibition of regeneration of vitamin K in the vitamin K epoxide cycle. The drug target is vitamin K epoxide reductase complex 1 (VKORC1). This results in inhibition of the activity of coagulation factors II, VII, IX and X. The effect occurs within 24 hours and reaches a maximum after up to 96 hours. The duration of action of a single dose is in the range of 2 to 5 days. Warfarin has a long half-life of approximately 40 hours (phenprocoumon: 160 hours).
Indications
- For prevention and treatment of thromboembolic disease.
- For long-term treatment of myocardial infarction at increased risk of thromboembolic complications.
Warfarin was originally used as a mouse and rat poison.
Dosage
According to the SmPC. Dose is individualized and adjusted and monitored according to prothrombin time (INR).
Contraindications
Numerous precautions must be observed during use. Full details can be found in the SmPC.
Interactions
Warfarin is a substrate of CYP450 isoenzymes (CYP2C9, 2C19, 2C8, 2C18, 1A2, and 3A4). The more potent -enantiomer is metabolized by CYP2C9. Warfarin has a high potential for drug-drug interactions with numerous agents.
Adverse effects
The most common potential adverse effects include bleeding from various organs and skin rashes. Bleeding can rarely be fatal. Because of the narrow therapeutic range, precautions must be carefully observed. Vitamin K1 (phytomenadione) is used as an antidote.
