Pharmacogenetics: An important piece of the treatment plan to help the patient feel better faster

Drug therapy is one of the greatest medical achievements, leading to the cure for numerous infectious diseases and treatment for multiple common health conditions including heart disease, cancer, and mental illness. For many Americans, especially as they age, it may be necessary to take multiple prescriptions to manage additional health issues. In fact, about 66% of American adults take at least 1 prescription and approximately 20% take 5 or more.¹ Unfortunately, not all medications work as intended for all people. Decreased efficacy and adverse drug reactions are common problems that have significant personal and financial costs. in 2022 there were over 1.25 million serious adverse drug reactions reported and nearly 175,000 deaths.² Thus, identifying ways to optimize medication therapy is crucial.

Variability in medication response can be due to many factors, including underlying organ dysfunction, age, weight, drug-drug interactions, diet, compliance, and genetics, to name a few. The importance of genetic variation in influencing drug response is becoming increasingly recognized by healthcare professionals and healthcare systems alike.

Pharmacogenetics, pharmacogenomics, and PGx are terms often used interchangeably that refer to how genetic variants influence drug response. A number of genetic variants are known to influence medication efficacy and/or toxicity. Knowing which pharmacogenetic variants a patient carries can help clinicians, along with their patients, make more informed decisions, optimize therapy, and reduce adverse drug reactions. 

For instance, some people who take statins to reduce cholesterol experience adverse symptoms like muscle aches, pains, weakness, cramps or fatigue. This is referred to as statin-associated musculoskeletal symptoms or SAMS. This can impact statin adherence and can impede the long-term effectiveness of statin therapy. There are several genes that can alter systematic exposure to various statins and influence the risk of SAMS:  SLCO1B1, CYP2C9, and ABCG2.³ Knowing about variations in these genes can allow the clinician to incorporate this information into the patient’s clinical history and choose the most appropriate drug and dosage to minimize this risk while still managing cholesterol.

Other examples of how pharmacogenetic testing can optimize therapy include variations in the gene for cytochrome P450 2C19 (CYP2C19) which can impact response to a number of medications including clopidogrel, citalopram, sertraline, some tricyclic antidepressants and others.^4-6 People who carry certain variants in another gene, DPYD, are at increased risk for severe, potentially life-threatening, adverse drug reactions if given the chemotherapeutic drugs 5-fluorouracil or capecitabine.⁷

Over 90% of patients will have at least one actionable pharmacogenetic variant.⁸ Knowing which important pharmacogenetic variants a patient carries helps clinicians make more informed choices on medication selection and dosages. Some examples of important gene-drug interactions are listed in the table below.

There are many different types of pharmacogenetic tests available. These tests can be thought of in terms of the breadth of medications they provide information for: 

Quest Diagnostics offers a polypharmacy pharmacogenomics panel. The testing provides information on 17 important genes and 4 HLA alleles. All genes on the panel have clinically actionable gene-drug associations. Pharmacogenomics Panel (test code 14272) will provide the clinician with the genetic results and the corresponding phenotype. No medication guidance is provided on this report. Clinicians wishing to get more information about how these genetic variations might impact various medications can select Pharmacogenomics Panel with InformedDNA, formerly Coriell Life Sciences (test code 14271), which will provide a link to InformedDNA’s clinical decision support tool for a report that has additional information showing various gene-drug interactions.     

Many, but not all, medications have actionable gene-drug interactions. Helpful websites include the Table of Pharmacogenetic Associations | FDA,¹¹ Table of Pharmacogenomic Biomarkers in Drug Labeling | FDA,¹² PharmGKB.org, and the Clinical Pharmacogenetics Implementation Consortium (CPIC®) at cpicpgx.org. These sites and their organizations can help determine whether pharmacogenetic testing might be useful for a particular medication and how a particular genetic variant might impact medication selection and dosage.

Optimizing therapy and reducing adverse drug events is critical for patients and healthcare systems. It requires consideration of all important factors, including genetic variants that can impact drug response. Pharmacogenetic testing can provide critical insights into medication response and is an important piece of a more complete clinical picture.

1. Prescription drugs. Health Policy institute website. Georgetown University.   Accessed May 19, 2025. https://hpi.georgetown.edu/rxdrugs/
2. Kommu S, Carter C, Whitfield P. Adverse drug reactions. In: StatPearls. StatPearls Publishing; 2024. https://www.ncbi.nlm.nih.gov/books/NBK599521/
3. Cooper-DeHoff RM, Niemi M, Ramsey LB, et al. The Clinical Pharmacogenetics Implementation Consortium guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and statin-associated musculoskeletal symptoms. Clin Pharmacol Ther. 2022;111(5):1007-1021. doi:10.1002/cpt.2557 
4. Lee CR, Luzum JA, Sangkuhl K, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 genotype and clopidogrel therapy: 2022 update. Clin Pharmacol Ther. 2022;112(5):959-967. doi:10.1002/cpt.2526 
5. Bousman CA, Stevenson JM, Ramsey LB, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A genotypes and serotonin reuptake inhibitor antidepressants. Clin Pharmacol Ther. 2023;114(1):51-68. doi:10.1002/cpt.2903
6. Hicks JK, Sangkuhl K, Swen JJ, et al. Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther. 2017;102(1):37-44. doi:10.1002/cpt.597
7. Amstutz U, Henricks LM, Offer SM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing: 2017 update. Clin Pharmacol Ther. 2018;103(2):210-216. doi:10.1002/cpt.911
8. Krebs K, Milani L. Translating pharmacogenomics into clinical decisions: do not let the perfect be the enemy of the good. Hum Genomics. 2019;13(1):39.
   doi: 10.1186/s40246-019-0229-z
9. FDA. Table of pharmacogenetic associations. Updated October 26, 2022. Accessed May 22, 2025. https://www.fda.gov/medical-devices/precision-medicine/table-pharmacogenetic-associations
10. FDA. Table of pharmacogenomic biomarkers in drug labeling. Updated      September 23, 2024. Accessed May 22, 22025. https://www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling
11. Goetz, Matthew P et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and tamoxifen therapy. Clinical pharmacology and therapeutics. 2018;103,5 (5):770-777. doi:10.1002/cpt.1007
12. Theken KN, Lee CR, Gong L, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and nonsteroidal anti-inflammatory drugs. Clin Pharmacol Ther. 2020;108(2):191-200. doi:10.1002/cpt.1830