Warfarin

Is warfarin safe?

Warfarin is a medicine where the benefit and the danger come from the same effect. It slows blood clotting, which prevents strokes in atrial fibrillation and stops clots in the legs and lungs from growing. Too much of that effect causes bleeding, and the gap between enough and too much is narrow.

That is why warfarin carries a boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary for major or fatal bleeding, needs regular blood tests, and was involved in a third of emergency hospital admissions for drug side effects among older Americans in one national study. We score it 49, a weak grade that reflects how much care it takes, not a reason to stop. Stopping without medical advice can cause a stroke.

The INR: a narrow target

Warfarin's effect is measured with the INR blood test. For most people the target is 2.0 to 3.0. Below that, clots can form; above about 4, bleeding risk climbs. The US label notes that bleeding is most likely in the first month and that keeping the INR in range does not remove the risk.

Doses vary more than tenfold between people because of age, weight, diet, other illnesses, other medicines and two genes (CYP2C9CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary and VKORC1). The label says to check the INR daily at the start until it is stable, then every 1 to 4 weeks.

How often does bleeding happen?

In the large atrial fibrillation trials that compared warfarin with newer anticoagulants, major bleeding on warfarin ran at about 3% of patients a year, with bleeding into the brain in under 1%. Real-world rates depend on how well the INR is controlled.

A CDC-led study published in 2011 estimated about 99,600 emergency hospital admissions a year for drug harm in Americans aged 65 and over between 2007 and 2009. Warfarin was involved in 33% of them, more than any other drug, followed by insulins (14%) and antiplatelet drugs such as aspirin and clopidogrel (13%).

Interactions: the biggest daily risk

Few medicines interact with as many things. Common examples:

Raises the INR (more bleeding)	Lowers the INR (more clotting)
Many antibiotics, including amoxicillin, co-trimoxazole and metronidazole	Rifampin
Fluconazole and other azole antifungals	Carbamazepine, phenytoin
Amiodarone	St John's wort
Regular acetaminophen	Large amounts of vitamin K from food or supplements
Heavy drinking binges	Some nutritional drinks

Separately, NSAIDs such as ibuprofen, aspirin and SSRI antidepressants such as sertraline raise bleeding risk without changing the INR much. Herbal products, including ginkgo, fish oil at high doses and turmeric, can matter too.

Missed doses, extra doses and reversal

Warfarin works slowly, over several days, so a single missed or extra tablet rarely causes immediate harm, but it does shift the INR. Never double up to make up for a missed dose. If you miss one or take too many, contact your anticoagulation clinic, pharmacist or doctor for advice on the next dose and whether you need an earlier INR test. A child who swallows warfarin, or anyone who has taken a large amount, needs urgent medical help: call Poison Control (1-800-222-1222) in the US or NHS 111 in the UK.

One advantage warfarin has over some newer blood thinners is that its effect can be reversed. Hospitals use vitamin K, which takes hours to work, and concentrated clotting factors for life-threatening bleeding.

Who should be careful

Everyone on warfarin should:

• carry an anticoagulant alert card and tell every doctor, dentist and pharmacist they take it
• keep vitamin K intake steady rather than cutting out greens
• ask a pharmacist before any new medicine, herbal remedy or supplement
• get urgent help after a head injury, even if they feel well

Warfarin is contraindicatedContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary in pregnancy except for some women with mechanical heart valves, because it can harm the baby. Older adults, people with past bleeding, kidney disease, high blood pressure or unstable INRs carry the highest risk. Ask your doctor whether a newer anticoagulant would suit you better.

How we scored it

Track record (95) and dependence (98) are strong, and vitamin K reverses its effect. Interactions (20), overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (30), regulatory warnings (35) and serious side effects (40) are all weak because of the narrow INR window, frequent bleeding and the long list of interacting drugs and foods.