Contact Connie Dello Buono 408-854-1883 motherhealth@gmail.com , certified rep at medxprime to avail of pharmacogenetic test if you are a doctor, and when prescribing Plavix.

CYP2C19 Genotype Test

Helping predict response to Plavix® (clopidogrel)

Carriers of one or two nonfunctional CYP2C19 variants may have:1-5,a,b

Differential response to Plavix

53% higher risk of a subsequent event in patients with cardiovascular disease (CVD) taking Plavix (300mg loading and 75mg daily mean dosages)

3-fold higher risk of stent thrombosis when taking Plavix

What is the CYP2C19 Gene?

The CYP2C19 gene encodes the cytochrome P450 2C19 enzyme. This enzyme plays an important role in the metabolism of many common drugs, such as the prodrug clopidogrel (Plavix), certain proton pump inhibitors (PPIs), and other drugs.7,a Multiple variants in the CYP2C19 gene have been found to alter the function of the cytochrome P450 2C19 enzyme.

CYP2C19 and Plavix Metabolism

The CYP2C19 Genotype Test identifies several metabolizer types.c The nonfunctional alleles are represented by *2, *3, *4, *5, *6, *7, *8, *9, and *12.  The increased function allele is represented by *17.  These variants alter the function of the CYP2C19 enzyme.d

Potential Clinical Implications

Poor and Intermediate metabolizers taking Plavix may have a higher risk of a subsequent CVD event including stent thrombosis

Ultra-rapid metabolizers have been shown to have enhanced metabolism of certain drugs and may have an increased risk of bleeding associated with Plavix use

Poor or Intermediate metabolizers may benefit from alternative dosing strategies or an anti-platelet medication other than Plavix

The FDA Warning Regarding Plavix

The FDA has placed a warning label on Plavix indicating that patients who are CYP2C19 poor metabolizers may not receive the full benefits of the drug:

“For Plavix to work, enzymes in the liver (particularly CYP2C19) must convert (metabolize) the drug to its active form. Patients who are poor metabolizers of the drug do not effectively convert Plavix to its active form. In these patients, Plavix has less effect on platelets, and therefore less ability to prevent heart attack, stroke, and cardiovascular death.”6 —FDA 2010

FDA Plavix Warning

The CYP2C19 Genotype Test was developed and its performance characteristics were determined by Berkeley HeartLab, a CLIA-certified and CAP-accredited laboratory. This test has not been cleared or approved by the U.S. FDA.

Plavix is a registered trademark of Sanofi-Aventis Corp.

1. The clinical impact of the CYP2C19 genotype on the metabolism of specific drugs will vary based on non-genetic factors, such as hepatic and renal status, other medications used (including over-the-counter medications, herbals, and other supplements), alcohol or illegal drug use, race, age, weight, diet, and diseases present in an individual patient.
2. Pharmacokinetic and pharmacodynamic analysis was performed on healthy individuals. Clinical outcomes data was performed primarily in Caucasian patients with acute coronary syndromes with planned PCI undergoing clopidogrel treatment.
3. Other rare alleles are not detected by this assay. Metabolism of drugs including clopidogrel may also be influenced by race, ethnicity, diet, and/or other medications.
4. Detection of CYP2C19 genetic variants does not replace the need for assessment of antiplatelet effectiveness and clinical monitoring.

References

Mega et al. Cytochrome P-450 Polymorphisms and Response to Clopidogrel. NEJM. 2009; 360:354-62

Sofi et al. Cytochrome P450 2C19*2 polymorphism and cardiovascular recurrences in patients taking clopidogrel: a meta-analysis. Pharmacogenomics Journal. 2010;1-8.

Sibbing et al. Cytochrome 2C19*17 Allelic Variant, Platelet Aggregation, Bleeding Events, and Stent Thrombosis in Clopidogrel-Treated Patients with Coronary Stent Placement. Circulation. 2010;121:512-518.

Simon et al. Genetic Determinants of Response to Clopidogrel and Cardiovascular Events. NEJM. 2009;360:363-375.

Li-Wan-Po et al. Pharmacogenetics of CYP2C19: functional and clinical implications of a new variant CYP2C19*17. British Journal of Clinical Pharmacology. 2009;69:3:222-230.

US Food and Drug Administration. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm203888.htm. Accessed February 13, 2012.

US Food and Drug Administration. http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm190848.htm. Accessed February 13, 2012.

Source: http://www.bhlinc.com/clinicians/test-descriptions/CYP2C19