Warfarin
Examples
Warfarin
Indications
Prophylaxis:
- Embolisation in rheumatic heart disease and atrial fibrillation
- After insertion of prosthetic heart valve
- Venous thrombosis
- Pulmonary embolism
- Venous thrombosis
- Pulmonary embolism
- Transient Ischaemic Attack
Contraindications
- Haemorrhagic Stroke
- Within 48 hours post-partum
- Significant Bleeding
- First trimester of pregnancy
- Severe hepatic impairment
- Bacterial endocarditis
- History of GI bleeding/peptic ulcer
- Hyperthyroidism
- Hypothyroidism
- Uncontrolled hypertension
- Recent Surgery
- Renal impairment
Mechanism
Warfarin (as a vitamin K antagonist) competitively blocks the function of the vitamin K epoxide reductase complex found in the liver, which diminishes the reduced form of vitamin K that serves as a cofactor for gamma carboxylation of vitamin K-dependent coagulation factors. This complex is needed to recycle vitamin K between its reduced and epoxide forms. This therefore inhibits factors II (aka prothrombin), VII, IX and X as they can’t bind to the calcium and phospholipid membranes needed for their function.
Administration
Oral
Adverse Reactions
- Haemorrhage
- Nausea/vomiting
- Alopecia
- Diarrhoea
- Calciphylaxis (most commonly found in patients with end stage renal disease).
Interactions
There have been reviews that show antivirals used to treat hepatitis C interact with warfarin, reducing efficacy so INR needs to be closely monitored.
There are scores of medications and foodstuffs that interact with warfarin, so must be checked before commencing on any medication/new diets.
There are scores of medications and foodstuffs that interact with warfarin, so must be checked before commencing on any medication/new diets.
Education
Patients should be made aware of the importance of frequent blood testing, especially during the dose adjustment stage.
Patients should also carry a warfarin alert card and be made of the vast numbers of interactions that warfarin has with OTC medicines and common foods and counselled appropriately.
Patients should also carry a warfarin alert card and be made of the vast numbers of interactions that warfarin has with OTC medicines and common foods and counselled appropriately.
Pharmacokinetics
Warfarin has nearly 100% bioavailability and a half-life of 36-42 hours, therefore a steady state may take more than 4 days to achieve.
Individuals with genetic variation in the CYP2C9 enzyme may find that lower doses are required, that it takes longer than other patients to reach the target INR, and that they have increased risk of bleeding.
