From the Guidelines
Pharmacogenetic testing is a crucial medical tool that helps doctors choose the best medications for patients by analyzing their genetic makeup to predict how they will respond to certain drugs. This test examines specific genes that affect how the body breaks down, absorbs, or responds to medications, allowing for personalized treatment plans that can help avoid adverse reactions and treatment failures 1. The goal of clinical pharmacogenomic testing is to examine genetic variants that are associated with interindividual variability in discrete aspects of pharmacology, such as drug metabolism, and to guide treatment strategies, including avoiding side effects and other harmful complications 1.
Key Points to Consider
- Pharmacogenetic testing can identify individuals who are at risk of severe idiosyncratic adverse events, helping medical professionals make informed decisions about choice of therapy, including using alternative strategies for treatment 1.
- The Clinical Pharmacogenetics Implementation Consortium (CPIC) develops peer-reviewed guidelines for pharmacogenetic testing based on evidence from randomized controlled trials and other clinical studies, focusing on gene-drug pairs for CLIA-approved genetic tests that show evidence for the need to change drug dose or consider an alternative drug 1.
- The test is simple, usually just a cheek swab or blood sample, and the results can guide doctors in selecting the right medication and dosage for patients, contributing to personalized or precision medicine 1.
- Pharmacogenomic testing can be used to identify individuals who are non-responders to certain medications or who may experience severe side effects, allowing for alternative treatment strategies to be implemented 1.
Current State of Pharmacogenetic Testing
- The field of pharmacogenetics is still developing, but it is becoming increasingly useful for medications used in psychiatry, cardiology, and pain management 1.
- There are many publicly available resources that support clinical pharmacogenomic testing, including the Pharmacogenomic Knowledgebase (PharmGKB), the Clinical Pharmacogenetics Implementation Consortium (CPIC), and the Pharmacogene Variation (PharmVar) Consortium 1.
- These resources provide evidence-based gene/drug clinical practice guidelines, catalogs of gene-based dosing guidelines, and lists of approved drug labeling that contain pharmacogenomic information, helping to optimize drug therapy and improve patient outcomes 1.
From the FDA Drug Label
The CYP2C19 gene 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 vivo platelet aggregation assays, differ according to CYP2C19 genotype Patients who are homozygous for nonfunctional alleles of the CYP2C19 gene are termed “CYP2C19 poor metabolizers.” Tests are available to identify patients who are CYP2C19 poor metabolizers.
Pharmacogenetic testing is a process that identifies how a person's genes affect their response to certain medications. In the case of clopidogrel, it involves testing for variations in the CYP2C19 gene, which can affect how the body metabolizes the drug.
- CYP2C19 poor metabolizers have a less effective response to clopidogrel, which may increase the risk of adverse cardiovascular events.
- Genetic testing can help identify patients who may be poor metabolizers, allowing for alternative treatments or adjusted dosing regimens to be considered.
- Pharmacogenomics is the study of how genes affect a person's response to medications, and it can help guide personalized treatment decisions 2.
- Warfarin is another medication that is affected by genetic variations, specifically in the CYP2C9 and VKORC1 genes, which can impact the dose required for effective anticoagulation 3.
From the Research
What is Pharmacogenetic Testing
Pharmacogenetic testing is a type of test that can identify patients who may benefit from personalized drug treatment 4. This testing can help identify patients at increased risk for medication toxicity, poor response, or treatment failure, and inform drug therapy 5.
How Does it Work
Pharmacogenetic testing can help identify genetic variations that affect how an individual responds to certain medications. For example, genetic variations in the CYP2C19 gene can affect how an individual responds to clopidogrel, a medication used to prevent blood clots 6, 7. Similarly, genetic variations in the VKORC1 gene can affect how an individual responds to warfarin, a medication used to prevent blood clots 6, 7.
Benefits of Pharmacogenetic Testing
The benefits of pharmacogenetic testing include:
- Improved treatment outcomes
- Reduced risk of medication toxicity
- Personalized drug treatment
- Increased clinical use of pharmacogenetic testing can benefit patients and society 4
Challenges and Limitations
Despite the potential benefits of pharmacogenetic testing, there are several challenges and limitations to its widespread adoption, including:
- Limited clinical uptake of pharmacogenetic testing
- Inconsistent testing recommendations between organizations and guidelines
- Need for standardized approach to evaluating the evidence of clinical utility for pharmacogenetic testing 4, 8
- Limited availability of high-quality primary studies and systematic reviews to assess the benefits of pharmacogenetic testing for certain diseases, such as cardiovascular diseases 7
Implementation in Clinical Practice
To implement pharmacogenetic testing in clinical practice, a stepwise approach can be used, including:
- Patient identification
- Pharmacogenetic test ordering
- Interpretation and application of test results
- Patient education 5