Clopidogrel: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on May 16, 2024.

1. How it works

• Clopidogrel inhibits the way platelets clump together (aggregate) to form clots and it may be used in several cardiovascular conditions to reduce the risk of a person having a stroke or a heart attack.
• The way clopidogrel works is thought to be due to its active thiol metabolite, which inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor which indirectly inhibits platelet aggregation. This action is irreversible. By inhibiting platelet aggregation, blood flows more freely around the body.
• Clopidogrel belongs to the class of medicines known as adenosine diphosphate (ADP) receptor antagonists (also called P2Y12 inhibitors). It is also a type of antiplatelet medicine.

2. Upsides

• Clopidogrel may be used to reduce the risk of stroke or heart attack in people with conditions such as unstable angina or following a heart attack (myocardial infarction). Clopidogrel should be administered in conjunction with aspirin.
• May also be given to people with established peripheral arterial disease or with a recent history of heart attacks or stroke to reduce the risk of further heart attacks or strokes.
• Can be administered as a loading dose (a bigger than normal, one-off dose) if an antiplatelet effect is needed within hours. Otherwise, it takes several days for the full antiplatelet effect of clopidogrel to develop with the usual dosage.
• The dosage of clopidogrel does not need adjusting in people with liver disease.
• Generic clopidogrel is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• An increased risk of bleeding from any wound, nosebleeds, blood in the urine, and an increased likelihood of bruising are the most commonly reported side effects.
• May also cause muscle pain, taste disorders, rash, and lower blood pressure.
• May cause a condition called Thrombotic Thrombocytopenic Purpura (TPP) - a blood disorder where blood clots form in the small blood vessels of the body. This can occur anytime during clopidogrel therapy, even after a short exposure (less than 2 weeks).
• Some people may not be as responsive to clopidogrel as others. Clopidogrel undergoes activation in the liver, through CYP2C19 hepatic enzymes. Some people have defective CYP2C19 enzymes which means they make less of the active metabolite of clopidogrel, and its antiplatelet effect is reduced (these people are termed poor metabolizers). Tests are available to identify patients who are CYP2C19 poor metabolizers and consideration should be given to using another platelet P2Y12 inhibitor in these patients.
• There is an increased risk of cardiovascular events when clopidogrel is discontinued. If clopidogrel needs to be temporarily discontinued (such as in the event of bleeding or before surgery that carries a major risk of bleeding), restart it as soon as possible. Clopidogrel may need to be discontinued up to five days before surgery with a high bleeding risk.
• Clopidogrel should not be used in people with an active peptic ulcer, following an intracranial hemorrhage, or who have active bleeding conditions. There is limited experience of using clopidogrel in people with moderate to severe kidney disease - caution is needed.
• May interact with several other drugs including those that inhibit CYP2C19 (such as omeprazole or esomeprazole), and those that also increase bleeding risk (such as SSRIs, SNRIs, NSAIDs, and warfarin).
• Human data have not identified an association between clopidogrel use in pregnancy and major birth defects, miscarriage, or adverse fetal outcomes. Animal studies corresponding to 65 to 78 times the recommended daily human dose revealed no evidence of impaired fertility or fetotoxicity due to clopidogrel. Weigh up the risks versus benefits because there are risks to the pregnant woman and fetus associated with myocardial infarction and stroke. Therapy for a pregnant woman should not be withheld because of potential concerns regarding the effects of clopidogrel on the fetus, if it is urgently needed. Clopidogrel use during labor or delivery will increase the risk of maternal bleeding and hemorrhage. Avoid neuraxial blockade during clopidogrel use because of the risk of spinal hematoma. When possible, discontinue clopidogrel 5 to 7 days before anticipated labor, cesarean delivery, or neuraxial blockade. There is no data on the presence of clopidogrel in human milk or the effects on milk production.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Clopidogrel may be given to reduce the risk of a heart attack or stroke in certain cardiovascular conditions or following a heart attack or ischemic stroke. People who are poor metabolizers of CYP2C19 may not respond very well to clopidogrel, because they make less of the active metabolite of clopidogrel. Bleeding is the most common side effect.

5. Tips

• May be taken with or without food.
• Take exactly as prescribed and do not discontinue except on a doctor's advice.
• Clopidogrel is often taken in conjunction with aspirin. Your doctor will advise you if you need to take aspirin as well.
• Do not take omeprazole or esomeprazole while taking clopidogrel as these will reduce its activity. Talk to a pharmacist or your doctor before buying any over-the-counter medicine to check if it is compatible with clopidogrel.
• You may notice that you bruise or bleed more easily and it will take longer to stop bleeding while you are taking clopidogrel. This shows that clopidogrel is working. However, if bleeding is excessive or prolonged, or you notice blood in your urine or stool, seek urgent medical advice.
• Seek prompt medical attention if you develop a fever, weakness, yellowing of the skin or eyes, feel confused, or your skin looks extremely pale.
• Tell your dentist and other health professionals that you are taking clopidogrel before an invasive procedure is scheduled.
• Tell your doctor if you are pregnant, intending to become pregnant, or breastfeeding before taking clopidogrel.

6. Response and effectiveness

• Clopidogrel is rapidly absorbed but has to undergo metabolism via CYP2C19 enzymes in the liver to its active form. People who are poor metabolizers of CYP2C19 will have a poor response to clopidogrel.
• Even though the active form of clopidogrel doesn't last for very long in the body, its effect on platelets lasts for the lifetime of the platelet. (7 to 10 days). Some inhibition of platelet clotting is seen within two hours of taking the drug; however, it takes between three to seven days of regular clopidogrel dosing to reach its maximal effect. Bleeding time and platelet aggregation return to baseline values within 5 days of treatment discontinuation.
• If the antiplatelet effect of clopidogrel needs to be reversed, platelet transfusions may be administered. However, these are less effective if given within 4 hours of a loading dose or 2 hours of a maintenance dose of clopidogrel.

7. Interactions

Medicines that interact with clopidogrel may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with clopidogrel. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with clopidogrel include:

• amiodarone
• apixaban
• bupropion
• calcium channel blockers
• corticosteroids, such as prednisone and methylprednisone
• dabigatran
• desloratadine
• erythromycin
• esomeprazole, omeprazole, or pantoprazole
• fentanyl
• fluconazole, ketoconazole, or voriconazole
• grapefruit juice
• lithium
• medications for gout, such as probenecid
• methotrexate
• mifepristone
• NSAIDs, such as celecoxib, ibuprofen, diclofenac, etodolac, and naproxen
• ticlopidine
• tinzaparin
• warfarin and other anticoagulants.

In general, any medicine that can increase the risk of bleeding (such as aspirin, SSRI antidepressants [eg, citalopram, duloxetine, fluoxetine, venlafaxine], fish oils) may interact with clopidogrel.

Note that this list is not all-inclusive and includes only common medications that may interact with clopidogrel. You should refer to the prescribing information for clopidogrel for a complete list of interactions.

References

• Clopidogrel. Revised 03/2024. Macleods Pharmaceuticals Ltd. https://www.drugs.com/pro/clopidogrel.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use clopidogrel only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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