What is the basic information behind pharmacogenetic (PGx) testing?

From the Guidelines

Pharmacogenetic testing is a crucial tool for personalized medicine, allowing clinicians to tailor medication selection and dosing to an individual's unique genetic profile, thereby minimizing adverse effects and optimizing therapeutic outcomes. This testing analyzes how a person's genetic makeup affects their response to medications, identifying genetic variations that influence drug metabolism, efficacy, and potential side effects. The process typically involves collecting a DNA sample through blood, saliva, or cheek swabs, which is then analyzed for specific genetic markers known to affect drug response, such as CYP2D6, CYP2C19, and CYP2C9, as discussed in 1.

Key Aspects of Pharmacogenetic Testing

• Common genes tested include CYP2D6, CYP2C19, and CYP2C9, which encode enzymes responsible for metabolizing many medications, including antidepressants like fluoxetine, pain medications like codeine, and anticoagulants like warfarin, as noted in 1.
• Results categorize patients as poor, intermediate, normal, or ultra-rapid metabolizers, helping clinicians adjust medication choices and dosages accordingly, as seen in 1.
• For example, a CYP2D6 poor metabolizer might receive a lower dose of certain antidepressants to avoid toxicity, while an ultra-rapid metabolizer of CYP2C19 might need a higher dose of clopidogrel (Plavix) to achieve therapeutic anticoagulation, as discussed in 1.

Clinical Utility and Recommendations

• The clinical utility of pharmacogenetic testing continues to grow as more gene-drug interactions are discovered and validated, though insurance coverage varies widely, as mentioned in 1.
• The Clinical Pharmacogenetics Implementation Consortium (CPIC) provides evidence-based gene/drug clinical practice guidelines, which can help clinicians make informed decisions about medication selection and dosing, as noted in 1.
• Preemptive pharmacogenomic testing can be an effective tool to enhance medication safety and efficacy, as discussed in 1, and its implementation should be considered in clinical practice to improve patient outcomes.

From the FDA Drug Label

CYP2C19 is involved in the formation of both the active metabolite and the 2-oxo-clopidogrel intermediate metabolite. Clopidogrel active metabolite pharmacokinetics and antiplatelet effects, as measured by ex vivoplatelet aggregation assays, differ according to CYP2C19 genotype Patients who are homozygous for nonfunctional alleles of the CYP2C19 gene are termed “CYP2C19 poor metabolizers.” Approximately 2% of White and 4% of Black patients are poor metabolizers; the prevalence of poor metabolism is higher in Asian patients (e.g., 14% of Chinese). Tests are available to identify patients who are CYP2C19 poor metabolizers.

The basic information behind pharmacogenetic testing for clopidogrel is that it involves testing for the CYP2C19 genotype, which can affect the formation of the active metabolite of clopidogrel.

• CYP2C19 poor metabolizers have decreased active metabolite exposure and diminished inhibition of platelet aggregation.
• The prevalence of CYP2C19 poor metabolizers varies by ethnicity, with approximately 2% of White, 4% of Black, and 14% of Chinese patients being poor metabolizers.
• Pharmacogenetic testing can identify patients who are CYP2C19 poor metabolizers, which can inform treatment decisions 2.

From the Research

Basic Information Behind Pharmacogenetic Testing

• Pharmacogenetic testing is used to identify patients who may benefit from personalized drug treatment 3
• It involves analyzing an individual's genetic profile to determine how they will respond to certain medications 4
• The goal of pharmacogenetic testing is to tailor treatment based on a patient's genetic profile, as well as their clinical factors, to improve patient outcomes 4

Key Genes Involved in Pharmacogenetic Testing

• CYP2D6 and CYP2C19 are two genes that have been extensively studied in relation to pharmacogenetic testing 5, 6
• Variants in these genes can affect an individual's response to certain medications, such as antidepressants and antipsychotics 5, 6
• Other genes, such as HLA-B*57:01 and G6PD, are also important in pharmacogenetic testing, particularly for certain medications like abacavir and rasburicase 3

Benefits of Pharmacogenetic Testing

• Pharmacogenetic testing can help improve treatment outcomes by avoiding non-response or severe side effects to certain medications 5, 6
• It can also help identify patients who are more likely to experience adverse effects or sub-therapeutic response to certain medications 7
• Studies have shown that providing genotypic information to physicians can be beneficial, particularly for non-extensive metabolizing patients 5, 6

Clinical Practice Guidelines for Pharmacogenetic Testing

• Clinical practice guidelines recommend biomarker tests that have demonstrated clinical utility, meaning that testing improves treatment outcomes 3
• However, the inclusion and consistency of pharmacogenetic testing recommendations in clinical practice guidelines can be limited and inconsistent 3
• A standardized approach to evaluating the evidence of clinical utility for pharmacogenetic testing may increase the inclusion and consistency of pharmacogenetic testing recommendations in clinical practice guidelines 3