Drug Detail:Plavix (Clopidogrel [ kloe-pid-oh-grel ])
Drug Class: Platelet aggregation inhibitors
1. How it works
- Plavix is a brand (trade) name for clopidogrel which inhibits the way platelets clump together (aggregate) to form clots and it may be used in several cardiovascular conditions to reduce the risk of the person having a stroke or a heart attack.
- Its activity is thought to be due to its active 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.
- Plavix belongs to the class of medicines known as P2Y12 inhibitors. It is also a type of antiplatelet medicine.
2. Upsides
- Plavix may be used for the treatment of unstable angina and for certain types of heart attack (myocardial infarction) to reduce the risk of stroke or heart attack. Plavix 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 a further heart attack or stroke.
- 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 Plavix to develop with the usual dosages.
- The dosage of Plavix does not need adjusting in people with liver disease.
- Plavix is available as a generic under the name clopidogrel.
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. The risk of this side effect is increased when Plavix is taken with other drugs that also increase bleeding risk (such as SSRIs - a type of antidepressant).
- May also cause muscle pain, taste disorders, rash, and lower blood pressure.
- There is an increased risk of cardiovascular events when Plavix is discontinued. If Plavix 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. Plavix may need to be discontinued up to five days before surgery with a high risk of bleeding.
- 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 Plavix therapy, even after a short exposure (less than 2 weeks).
- Some people may not be as responsive to Plavix as others. Plavix undergoes activation in the liver, through CYP2C19 hepatic enzymes. Some people have defective CYP2C19 enzymes which means they make less active drug from 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.
- Plavix 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 Plavix for 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 Plavix 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 pregnant women should not be withheld because of potential concerns regarding the effects of clopidogrel on the fetus. Plavix use during labor or delivery will increase the risk of maternal bleeding and hemorrhage. Avoid neuraxial blockade during Plavix use because of the risk of spinal hematoma. When possible, discontinue Plavix 5 to 7 days before labor, delivery, or neuraxial blockade. There are no data on the presence of Plavix 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. Tips
- May be taken with or without food.
- Take exactly as prescribed and do not discontinue except on a doctor's advice.
- Plavix 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 Plavix 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 Plavix.
- You may notice that you bruise or bleed more easily and it will take longer to stop bleeding while you are taking Plavix. This shows that Plavix 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 Plavix before an invasive procedure is scheduled.
- Tell your doctor if you are pregnant, intending to become pregnant, or breastfeeding before taking Plavix.
5. Response and effectiveness
- Plavix is rapidly absorbed but has to undergo metabolism via CYP2C19 enzymes in the liver to its active form. People who are poor metabolizers at CYP2C19 will have a poor response to Plavix.
- Even though the active form of Plavix 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 Plavix 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 Plavix 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 Plavix.
6. Interactions
Medicines that interact with Plavix may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Plavix. 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 Plavix 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 Plavix.
Note that this list is not all-inclusive and includes only common medications that may interact with Plavix. You should refer to the prescribing information for Plavix for a complete list of interactions.