Clopidogrel, by Sanofi-Synthelabo.

How does it work?

Plavix tablets contain the active ingredient clopidogrel hydrogen sulphate, which is a type of medicine called an antiplatelet (sometimes referred to as a 'blood-thinning' medicine). It stops blood cells called platelets from clumping together and forming blood clots.

Clopidogrel works by preventing a natural substance called ADP from binding to its receptors on platelets. ADP is one of the chemicals in the body that cause platelets to clump together and start the process of blood clotting. As clopidogrel stops ADP from binding to platelets, it reduces the likelihood of clots forming in the blood.

A blood clot that forms inside the blood vessels is known as a thrombosis and can be dangerous, as it can cause a blockage that cuts off the blood supply to an organ. A blockage in the arteries supplying blood to the heart or brain can cause a heart attack or stroke. A blockage in the blood vessels in the extremities, eg legs, may result in gangrene.

Blood clots and blockages mainly result from a build up of atherosclerosis on the inside of blood vessels. Atherosclerosis is a build up of cholesterol and fat cells that narrows the blood vessels and makes their interiors rough and bumpy. This makes it more difficult for blood to flow through the vessels, and increases the likelihood of clots forming in the vessels.

People who have already suffered a heart attack or stroke are at risk of having another because of the atherosclerosis in their arteries. People with unstable angina are also at risk of a heart attack because of the atherosclerosis in their arteries. Similarly, people who have narrowed arteries in their extremities, eg legs (peripheral arterial disease), are also at risk of blood clots. These events are known as atherothrombotic events. Clopidogrel is used to prevent blood clots forming within blood vessels, and therefore reduce the risk of further atherothrombotic events in these groups of people.

What is it used for?

• Reducing risk of atherothrombotic events (eg further heart attacks) in people who have had a heart attack.
• Reducing risk of atherothrombotic events (eg further strokes) in people who have had a stroke caused by a blood clot (ischaemic stroke).
• Reducing risk of atherothrombotic events in peripheral arterial disease.
• Reducing risk of atherothrombotic events (eg heart attack, stroke, further heart attacks or death) in people having severe chest pain caused by unstable angina or a heart attack (in this case the medicine is given in combination with aspirin as part of other emergency treatment).

Warning!

• It may take longer than normal for you to stop bleeding, for example if you accidentally cut yourself, while you are taking this medicine. This is not normally a problem. However, you should tell your doctor promptly if you experience any unexplained bruising or unusual bleeding (eg bleeding from an unusual site or that takes a very long time to stop), particularly if also accompanied by a fever, signs of infections, extreme tiredness or feeling generally unwell. Your doctor may want to take a blood sample to check there are no problems with the number of blood cells in your blood.
• Your doctor may ask you to stop taking this medicine a week before any planned surgery, including dental surgery, as it may prolong any bleeding. Discuss this with your doctor.

Use with caution in

• People at increased risk of bleeding due to surgery, injury or disease.
• People taking other medicines that increase the risk of bleeding (see end of factsheet for examples).
• Decreased kidney function.
• Moderate liver disease.

Not to be used in

• People with any active bleeding, for example from a peptic ulcer or brain haemorrhage.
• Severely decreased liver function.
• First week following an ischaemic stroke.
• Pregnancy.
• Breastfeeding.
• Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption (Plavix tablets contain lactose).
• The safety and efficacy of this medicine in children and adolescents under 18 years of age has not been established. It is not recommended for this age group.

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

• There is no information available about the safety of this medicine for use during pregnancy. The manufacturer states that it is not recommended for use during pregnancy. Seek medical advice from your doctor.
• It is not known if this medicine passes into breast milk. The manufacturer states that it should not be used during breastfeeding. Mothers who need to take this medicine should not breastfeed. Seek further medical advice from your doctor.

Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here does not mean that all people using this medicine will experience that or any side effect.

Common (affect between 1 in 10 and 1 in 100 people):

• Bleeding, for example nosebleeds, bleeding at injection sites, bleeding in the stomach or bowels.
• Bruising.
• Diarrhoea.
• Abdominal pain.
• Indigestion.

Uncommon (affect between 1 in 100 and 1 in 1000 people):

• Increased time taken to stop bleeding.
• Blood in the urine.
• Bleeding in the skin (purpura).
• Bleeding in the eyes or brain.
• Decrease in the number of platelets in the blood (thrombocytopenia).
• Disturbances in the numbers of white blood cells in the blood.
• Rash or itching.
• Nausea and vomiting.
• Constipation.
• Wind.
• Ulceration in the stomach or intestines.
• Inflammation of the stomach (gastritis).
• Headache.
• Dizziness.
• Pins and needles sensations (paraesthesia).

The side effects listed above may not include all of the side effects reported by the medicine's manufacturer.

For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while taking this one, to ensure that the combination is safe.

There may be an increased risk of bleeding if clopidogrel is taken in combination with the following medicines, which also affect blood clotting:

• aspirin
• dipyridamole
• glycoprotein IIb/IIIa inhibitors, eg abciximab, eptifibatide, tirofiban
• heparin
• iloprost
• low molecular weight heparin, eg dalteparin
• medicines that break down blood clots (thrombolytics), eg alteplase, streptokinase
• non-steroidal anti-inflammatory drugs (NSAIDs), eg naproxen, ibuprofen, diclofenac
• oral anticoagulants such as warfarin (clopidogrel is not recommended for use in combination with oral anticoagulants)
• SSRI antidepressants, eg fluoxetine, paroxetine
• venlafaxine.

You should be carefully monitored for any signs of bleeding during the first weeks of treatment with clopidogrel, and following any surgery, if you are also taking any of the medicines listed above.

There have been some recent studies that suggest that if a type of medicine called a proton pump inhibitor (PPI, for example omeprazole or lansoprazole) is used in combination with clopidogrel, it may make the clopidogrel less effective, thus increasing the risk of further heart attacks and death. However, some other studies of the combination have not found evidence to support this interaction. This issue is still under review and debate, and will need further study. However, if you are currently taking a proton pump inhibitor in combination with clopidogrel, you should consult your doctor to discuss this. Your doctor may feel that on balance you don't need to take the proton pump inhibitor because you are not at high risk of an ulcer, or that a different type of medicine may be more appropriate until it is known for sure what effect PPIs have on clopidogrel.