What is clopidogrel, and how does it work (mechanism of action)?
Clopidogrel bisulfate (Plavix) is an anti-platelet drug, that is, a drug that inhibits the ability of platelets to clump together as part of a blood clot. Clopidogrel prevents blood clots by irreversibly binding to the P2Y12 receptor on platelets, preventing adenosine diphosphate (ADP) from activating platelets. It belongs to a class of drugs called P2Y12 inhibitors. Other drugs in this class include ticagrelor (Brilinta) and prasugrel (Effient). Clopidogrel is similar to ticlopidine (Ticlid) in chemical structure and in the way it works. Unlike ticlopidine, clopidogrel bisulfate does not cause serious reductions of white cells in the blood and, therefore, routine blood testing to determine if the white blood cell count is low is not necessary during treatment. The risk of heart attacks and strokes (which usually are caused by blood clots) is increased in patients with a recent history of stroke or heart attack, and patients with peripheral vascular disease. (Peripheral vascular disease is the same as atherosclerotic arterial disease or "hardening" of the arteries in which the arteries become narrowed. It frequently occurs in the legs and often causes claudication or pain in the legs upon walking.) Clopidogrel bisulfate is used to reduce the risk of heart attacks and strokes in these patients. Clopidogrel bisulfate was approved by the FDA in 1997.
What are the uses for clopidogrel?
Clopidogrel is used for preventing strokes, heart attacks, and death in individuals who have had a previous stroke, unstable angina, heart attack or have peripheral arterial disease (PAD). The combination of clopidogrel and aspirin is better than aspirin or clopidogrel alone in preventing another heart attack but the risk of bleeding is higher.
What are the side effects of clopidogrel?
The tolerability of clopidogrel is similar to that of aspirin. The more common side effects of clopidogrel are:
- Abdominal pain
- chest pain,
- muscle aches,
- severe bleeding,
- allergic reactions,
- pancreatitis, and
- liver failure.
Ticlopidine (Ticlid) is an antiplatelet medication quite similar to clopidogrel. It has been associated with a severe reduction in white blood cell count in between 0.8% and 1% of persons. The risk of this dangerous side effect with clopidogrel is about 0.04%, much less than with ticlopidine but twice that of aspirin.
Clopidogrel rarely causes a condition called thrombotic thrombocytopenic purpura (TTP) in one out of every 250,000 people. TTP is a serious condition in which blood clots form throughout the body. Blood platelets, which participate in clotting, are consumed, and the result can be bleeding because enough platelets are no longer left to allow blood to clot normally. For comparison, the related drug, ticlodipine (Ticlid), causes TTP 17-50 times more frequently than clopidogrel.
In the U.S., 1 in every 4 deaths is caused by heart disease.
What is the dosage for clopidogrel?
Clopidogrel bisulfate usually is taken once daily. It can be taken with or without food. Clopidogrel is activated by enzymes in the liver to its active form. Individuals who have reduced activity of liver enzymes that activate clopidogrel due to liver disease may not adequately respond to clopidogrel. Alternative treatments should be used for these patients. The recommended dose for treating unstable angina or heart attack is 300 mg initially followed by 75 mg daily in combination with 75-325 mg of aspirin. Peripheral arterial disease or recent stroke is treated with 75 mg daily.
Which drugs or supplements interact with clopidogrel?
The combination of clopidogrel with nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Motrin, Advil, Nuprin), naproxen (Naprosyn, Aleve), diclofenac (Voltaren), etodolac (Lodine), nabumetone (Relafen), fenoprofen (Nalfon), flurbiprofen (Ansaid), indomethacin (Indocin), ketoprofen (Orudis; Oruvail), oxaprozin (Daypro), piroxicam (Feldene), sulindac (Clinoril), tolmetin (Tolectin), and mefenamic acid (Ponstel) may increase the risk of stomach and intestinal bleeding.
Clopidogrel is converted to its active form by enzymes in the liver. Drugs that reduce the activity of these enzymes, for example, omeprazole (Prilosec, Zegerid) or esomeprazole (Nexium) may reduce the activity of clopidogrel and should not be used with clopidogrel. Other drugs that also may react with clopidogrel in a similar fashion include fluoxetine (Prozac, Sarafem), cimetidine (Tagamet), fluconazole (Diflucan), ketoconazole (Nizoral, Extina, Xolegel, Kuric), voriconazole (Vfend), ethaverine (Ethatab, Ethavex), felbamate (Felbatol), and fluvoxamine (Luvox).
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Is clopidogrel safe to take if I’m pregnant or breastfeeding?
There are no adequate studies of clopidogrel in pregnant women.
Studies in rats have shown that clopidogrel appears in breast milk; however, it is not known whether it also appears in human breast milk. Because of a potential for side effects in the nursing infant, the physician must weigh the potential benefits and possible risks before prescribing clopidogrel to nursing mothers.
What else should I know about this drug?
- Clopidogrel is avaialable as tablets: 75 and 300 mg. Tablets should be stored at room temperature, 15 C – 30 C (59 F – 86 F).
- Clopidogrel is available as a generic drug. You need a prescription from your doctor to obtain this medicine.
- Plavix is the brand name available for clopidogrel in the US.