Drug Metabolism - Clopidogrel (Plavix) Activation

FDA warning: Some patients cannot process blood thinner Plavix

Clopidogrel is used to prevent heart attack & stroke by limiting platelet aggregation. It must first be processed by liver enzyme CYP2C19 to the active form of the drug. A third of the population has limited or no ability to process clopidogrel. They have 3-fold higher risk of heart attack, stroke & death. This is particularly important for patients undergoing percutaneous coronary intervention. Patients on clopidogrel should avoid omeprazole (Prilosec) as it limits activation of clopidogrel!

• Many people inherit the normal active CYP2C19*1 from both parents. They are able to process clopidogrel effectively and are called extensive metabolizers (EM).
• The common inactive forms of the enzyme are *2 & *3; there are also several infrequent nonfunctional forms *4, *5, *6, *7 & *8.
• Persons who inherit one inactive copy have reduced ability to process clopidogrel and are called intermediate metabolizers (IM). They require a higher dose.
• Those who inherit two inactive copies have little or no ability to process clopidogrel and are called poor metabolizers (PM). Another drug should be used.
• Several percent of the population carries a very active form of the enzyme called CYP2C19*17 having increased activity to process clopidogrel. Here, again, dose should be adjusted upwards.
• Table 1 shows the frequency of EM, IM & PM in the population. Persons of Asian and African ancestry are more likely to be poor metabolizers. 

Table 1. Frequency of extensive, intermediate & poor metabolizers in the population.

Our test identifies which forms of CYP2C19 have been inherited, and the expected level of enzyme activity (rapid, extensive, intermediate or poor). The FDA recommends obtaining this information. If you are a patient, share these results with your physician. While this information is expected to be extremely useful in determining clopidogrel dose, or choosing an alternative medication such as prasugrel, no claim is made that all aspects of clopidogrel metabolism are evaluated. CYP2C19 is needed to metabolize a number of other drugs including tamoxifen, the anticonvulsant mephenytoin, anti-ulcer drugs such as omeprazole (use H2 antagonists, instead), certain antidepressants, and the antimalarial drug proguanil. These medications may alter your needed dose of clopidogrel. It is essential that you discuss these issues with your physician before changing your treatment!