Understanding Pharmacogenomics Is Essential for Personalized Care

Pharmacogenomics is a growing area in the medical field. This field of study interprets the effect of one’s genes on their medications. It allows us to maximize the use of medication for more personalized treatment. The interaction between the drug and the body can be affected by specific genes, influencing the metabolism of drugs. Certain individuals can have rapid metabolism, or they can have poor metabolism. An individual with rapid metabolism will quickly metabolize the drug, which will lead to lower concentrations of the drug and not enough clinical effects. An individual with poor metabolism will slowly metabolize the drug, which will lead to higher concentrations of drugs and more toxicity.¹ Thus, it is important for pharmacists to understand pharmacogenomics to apply it to patients. It is also important to note that pharmacogenomics can play a role in reducing the cost of health care expenditures, such as shortening hospital stays and reducing emergency department visits.²

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Pharmacogenomics was first termed by Friedrich Vogel in 1959.³ This specific field of science grew recently because of the launch of the Human Genome Project. The goal of this project, which was run by the National Institutes of Health and the US Department of Energy’s Biological and Environmental Research program, was to sequence the whole human genome. This project ultimately became the forefront of personalized medicine. Today, investigators use technologies such as DNA microarrays, RNA expression studies, protein arrays, and DNA sequencing to study drug response.3 These technologies are related to pharmacogenomics because it studies the effects of genetic variation on the traits of drug response.

Laws and prospective bills such as the Genetic Information Nondiscrimination Act (GINA), Right Drug Dose Now Act, and Utilizing Pharmacogenomics to Greatly Reduce Adverse Drug Events (UPGRADE) Act were passed to further the pharmacogenomics movement. GINA, a law passed by the US Congress in 2008, prevents genetic discrimination from health insurance companies or employers.⁴ It prohibits insurance companies from using genetic information to deny coverage, adjust premiums, or impose restrictions. The Right Drug Dose Now Act is a bill that requires the National Human Genome Research Institute to carry out a public awareness campaign on adverse events (AEs) and establish a program to educate health care providers about pharmacogenomics testing and associated issues.⁵ Lastly, the UPGRADE Act adds pharmacogenomics testing as a covered benefit under Medi-Cal, a program that offers health care service to lowincome individuals. These laws are further expanding the pharmacogenomics field.⁶

Regarding bioethics, there are 4 fundamental principles.⁷ These principles are to have respect for other human beings as moral equals, avoid harming other humans by our actions, do good for other human beings and have more beneficial effects than harmful effects, and treat other human beings fairly. During the research and development process, it is important to ensure that consent is obtained before samples and genetic information are gathered so that the privacy of the participants is protected.⁷ It is also important to include a variety of racial and ethnic groups because certain genetic variants are more common in specific racial and ethnic groups than in others. Health professionals also need proper training to effectively communicate information about pharmacogenomics to their patients.

Pharmacogenomics has a significant impact on both drug discovery and clinical prescription. In drug development, it offers an effective pathway that improves efficiency and cost-effectiveness for pharmaceutical companies. By using genetic factors to guide the selection of potential drug candidates, pharmacogenomics simplifies the discovery process. This method also enhances the design of clinical trials, because patient groups can be tailored based on their genetic responses, leading to better trial results. Furthermore, pharmacogenomics enhances the assessment of drug effectiveness and safety, resulting in safer and more efficient treatments. Another valuable aspect involves the potential reevaluation of existing drugs, using genetic insights to uncover new clinical uses for drugs that are already available. Overall, the applications of pharmacogenomics empower both drug discovery and clinical prescribing by incorporating genetic data to optimize treatment approaches and patient outcomes.^8,9

Study design involves using planning and research to find out how or why an individual’s genetic characteristics may influence how they respond to a drug. By using the appropriate study design, one can discover the science behind an individual’s genetic characteristics and how these characteristics affect the efficacy, drug metabolism, and safety profile. Key aspects of pharmacogenomics include patient selection, genotyping, control groups, end points, data analysis, and ethical considerations. Researchers must carefully select study participants, considering factors such as genetic diversity, medical history, and the specific drug being studied. The overarching goal is to personalize medicine by tailoring drug treatments to match an individual’s genetic makeup.^8,9

Pharmacogenomic information is included in prescribing information (PI) if the information has important implications for the safe and effective use of a drug.¹⁰ Consequences of the genetic variation results will be summarized in the PI in different sections, such as indications and usage, dosage and administration, boxed warning/contraindications/warnings and precautions/AEs, drug interactions, clinical pharmacology, and clinical studies. For instance, under the drug interactions section, it may include information concerning the role of genetic variation in drug-drug interaction and its clinical consequences.¹⁰ Thus, it is always important to look at the PI to see which genetic variations can have effects.

An example of a medication that involves pharmacogenomic testing is abacavir, which is used to manage HIV infections. Hypersensitivity reactions limit the use of abacavir. If an individual has a positive result for the HLA-B*5701 allele, there will be a higher chance for hypersensitivity reactions. This resulted in a strong recommendation for HLA-B 5701 screening in the product labeling.¹¹ Clopidogrel, an antiplatelet medication, is another example, and it is metabolized to an active metabolite by cytochrome P450 (CYP) C19. If an individual has poor metabolism of CYP2C19, then there will be less exposure to the active metabolite in the body, leading to fewer clinical effects. This resulted in a product label containing information about decreased antiplatelet response with reduced CYP2C19 function.¹¹

Pharmacists play a vital role in pharmacogenomics. As medication experts with adequate pharmacogenomics training, pharmacists are best suited to identify the patients at risk. By interpreting the pharmacogenomics results, pharmacists can recognize the risk for AEs and treatment failure. Pharmacists can provide critical information regarding pharmacogenomics and create personalized plans for each patient. Pharmacists can continue to educate other health care professionals and patients about the importance of pharmacogenomics.

About the Author

Vanessa Bravo is a 2024 PharmD candidate at Temple University School of Pharmacy in Philadelphia, Pennsylvania. She works at a local community pharmacy and is pursuing a master’s degree in global clinical and pharmacovigilance regulations.

Sarah John is a 2024 PharmD candidate at Temple University in Philadelphia, Pennsylvania. She works in a community pharmacy and a hospital pharmacy setting. Previously, she was president of the Phi Lambda Sigma chapter, international vice president of the American Pharmacists Association, and vice president of the Pediatric Pharmacy Advocacy Group at Temple University.

Fanny Kusi is a 2024 PharmD candidate at Temple University School of Pharmacy in Philadelphia, Pennsylvania. She is pursuing a master’s degree in global clinical and pharmacovigilance regulations and is a first-generation college student.

References

1. What everyone needs to know about drug metabolism. Genomind. February 12, 2021. Accessed August 4, 2023. https://genomind.com/patients/what-everyone-needs-to-know-about-drugmetabolism/#:~:text=Poor%20metabolizers%20have%20significantly%20reduced,metabolizers%20have%20high%20enzyme%20activity
2. Understand how variations in the human genome affect our response to medications. Illumina. Accessed August 4, 2023. http://www.illumina.com/areas-of-interest/pharmacogenomics.html
3. Srivastava A, Guin D, Kukreti R, Vohora D. Chapter 7 - pharmacogenomics: an evolution towards clinical practice. In: Vohora D, Singh G, eds. Pharmaceutical Medicine and Translational Clinical Research. Academic Press; 2017:107-127.
4. Genetic information discrimination. US Equal Employment Opportunity Commission. Accessed August 4, 2023. http://www.eeoc.gov/geneticinformation-discrimination
5. Right Drug Dose Now Act, HR 6875, 117th Cong (2021-2022). Accessed August 4, 2023. https://www.congress.gov/bill/117th-congress/housebill/6875
6. Medi-Cal: Pharmacogenomic Testing. SB 1191. 2021-2022 Session (Ca 2022). Accessed August 20, 2023. http://www.pluralpolicy.com/app/legislativetracking/bill/details/state-ca-20212022-sb1191/1030972
7. Varkey B. Principles of clinical ethics and their application to practice. Med Princ Pract. 2021;30(1):17-28. doi:10.1159/000509119
8. Ritchie MD. The success of pharmacogenomics in moving genetic association studies from bench to bedside: study design and implementation of precision medicine in the post-GWAS era. Hum Genet. 2012;131(10):1615-1626. doi:10.1007/s00439-012-1221-z
9. Ross S, Anand S, Joseph P, Paré G. Promises and challenges of pharmacogenetics: an overview of study design, methodological and statistical issues. JRSM Cardiovasc Dis. 2012;1(1):cvd.2012.012001.doi:10.1258/cvd.2012.012001
10. US Department of Health and Human Services; FDA; Center for Drug Evaluation and Research; Center for Biologics Evaluation and Research; Center for Devices and Radiological Health. Guidance for industry: clinical pharmacogenomics: premarket evaluation in early-phase clinical studies and recommendations for labeling. January 2013. Accessed August 4, 2023. https://www.fda.gov/regulatory-information/search-fda-guidancedocuments/clinical-pharmacogenomics-premarket-evaluation-earlyphase-clinical-studies-and-recommendations
11. Table of pharmacogenetic associations. FDA. October 26, 2022. Accessed August 4, 2023. http://www.fda.gov/medical-devices/precision-medicine/table-pharmacogenetic-associations#section2