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Legal classification of drug

POM

Warfarin tablets can only be obtained in accordance with a prescription given by an appropriate practitioner and therefore the legal status of the medication is prescription only medication (POM).

Warfarin is available in tablet form. The tablets come in 500mcg (0.5mg), 1mg, 3mg, and 5mg strengths.

Class of drug

Warfarin is an anticoagulant drug.

Indications

• Deep vein thrombosis (formation of blood clots).
• Prevention of embolism (clots which detach themselves and travel to other parts of the body) in patients who have atrial fibrillation (AF) and rheumatic heart disease.
• Prevention of embolism in patients who have mechanical prosthetic heart valves.
• Prevention of heart attack and stoke.

How does it work?

Blood clotting is a complex process which involves clotting factors that are activated by vitamin k. Warfarin slows down the production of vitamin K in the body therefore increasing the time it takes for the blood to clot.

How is it taken?

A starting dose of 10mg daily is given for the first two days but this should be tailored to individual requirements. The daily maintenance dose is usually between 3-9mg daily taken on the same time of each day. The exact dose given will depend upon the prothrombin time, reported as INR (international normalised ratio).

The international normalised ratio (INR) is a test which measures how long it takes for the blood to clot. The dose of warfarin that needs to be taken will depend on the INR, if the result is out of range for a particular condition the dose of warfarin may need to be increased or decreased accordingly. It is essential that INR be measured daily or on alternative days at beginning of treatment then at longer intervals depending on response.

Pregnancy and Breast feeding

Warfarin should be avoided during pregnancy as it crosses the placenta with risk of placental or foetal haemorrhage.

Warfarin dose not pose a greater risk to mothers who are breast feeding.

Contra-indications

• Ulcers within the stomach or small intestine (gastric or peptic ulcers).
• Severe high blood pressure.
• Pregnancy.

Side-effects

The main side-effect of warfarin therapy is bleeding (haemorrhage). This can be avoided by regularly checking INR and not taking doses which are not essential. Other side-effects include:

• Rash
• Hair loss
• Diarrhoea
• Jaundice
• Nausea
• Vomiting
• Drop in red blood cell count often giving rise to symptoms called ‘purple toes’

Drug Interactions with warfarin

Warfarin is termed a drug which has a narrow therapeutic range, this means any slight decrease or increase in warfarin levels with the blood can cause side-effects and also dose adjustments will be required, i.e. if a drug interacts with warfarin and decreases the metabolism of warfarin, then an increase in the dose of warfarin will be required to compensate for the interaction and vise-versa. The following is a list of drugs which interact with warfarin and should be avoided unless directed by the GP or specialist clinic.

• Non-steroidal anti-inflammatory drugs (NSAID’s), i.e. ibuprofen, diclofenac, aspirin enhance the anticoagulant effect of warfarin therefore increasing the risk of bleeding.
• Increased risk of bleeding when taken with tramadol.
• INR is altered when warfarin is given with certain antibiotics, i.e. erythromycin, clarithromycin, trimethoprim, oxytetracycline, azithromycin, cefalexin, metronidazole. These antibiotics possiblly enhance the effect of warfarin.
• Antidepressants such as venlafexine, serotonin re-uptake inhibitors (SSRI’s) such as fluoxetine, citalopram, sertraline, and tricyclic antidepressants such as amitriptyline enhance the anticoagulant effect.
• Antiepileptics increase the breakdown of warfarin therefore reducing the anticoagulant effect, examples of antiepileptic drugs causing this interaction include carbamazepine and phenytoin.
• Anticoagulant effect of warfarin is enhanced when given with levothyroxine tablets.
• Azathioprine should be avoided as it increases the anticoagulant effect.

This list not exhaustive if in doubt contact your GP or pharmacist. Warfarin also interacts with many other medicines and food products. Elderly patients normally buy glucosamine tablets for their joints. Glucosamine interacts with warfarin increasing the risk of bleeding and therefore its use should be avoided. Consuming very large quantities of ice-cream many also alter INR levels. Green vegetables containing large quantities of vitamin K interact with warfarin reducing its desired use. Warfarin is also known to interact with St John’s wort this combination should also be avoided as the effects on warfarin are unpredictable.

Author: Mr Shiraz Mughal, MPharmS
Editor: Dr Shazan Chughtai, MB BS