By Kathy O’Brien, MS CGC | Genomic Services, Quest Diagnostics

March 12, 2019 Better Health

When it comes to medication, one size may not fit all. Many patients are taking medications that do not work well for them or that cause unwanted side effects.

There are many reasons for differences in drug effectiveness and response, including a person’s height and weight, health problems, genetic make-up, other medications, food, and/or the environment.

Adverse drug reactions represent one of the major causes of hospitalization and genetic factors may contribute to a significant proportion of these events. Knowing important genetic information can help reduce the likelihood of these events. 1 Pharmacogenomics is the study of how genetic differences impact the way drugs or medications affect a person. These genetic differences can impact the way a drug is processed by the body, which can influence drug response. Pharmacogenomic tests may provide information about a person’s genetic makeup to help doctors make medication decisions. Specifically, it may enable healthcare professionals to determine the best dose of a medication or to know which medications to avoid or monitor closely because of potential side effects or lack of personal effectiveness.

Pharmacogenomic tests can help explain why a certain drug does not work for a person or causes a serious adverse reaction in another. Using such testing can help doctors decide on whether an alternative drug might be more appropriate, whether adjusting the dose may be necessary or whether additional follow up and monitoring is needed. Pharmacogenomic testing can be used by physicians in multiple specialties. For instance, codeine is a medication often prescribed for pain. Certain individuals may have a genetic change that causes them to produce too much or too little of an enzyme called cytochrome P450 2D6 (CYP 2D6). This enzyme, which is mostly expressed in the liver, is involved in the metabolism of many different medications, including codeine. Having too little of this enzyme can reduce the medication’s effectiveness in controlling pain and having too much of this enzyme can lead to serious side effects. 3 In addition, pharmacogenomics is becoming an increasingly useful tool by mental and behavioral health professionals. CYP 2D6 also impacts the metabolism of tricyclic antidepressants.  Other medications used to treat depression and other mental illnesses may also be influenced by genetics. 4,5 Patients may have to try many medications before finding one that works best for them. Pharmacogenetic testing may help reduce this trial-and-error period for some patients.

Currently, there are over 600 drugs for which genetic differences are known or suspected to play a part in how well the drug works. 2 For some medications, the relationship is strong and clear and there are dosing guidelines available for physicians to use. For other drugs, there is emerging information on possible genetic associations, but more studies are necessary to better define them.

You can find more information about pharmacogenomic testing by speaking with your physician or by visiting web sites like https://www.genome.gov/27530645/faq-about-pharmacogenomics/; https://www.fda.gov/Drugs/ScienceResearch/ucm572698.htm .

References

1) Manolopoulos VG. Pharmacogenomics and adverse drug reactions in diagnostic and clinical practice.Clin Chem Lab Med. 2007;45(7):801-814. doi: 10.1515/CCLM.2007.184

2) https://www.pharmgkb.org/annotatedDrugs

3) Crews KR, Gaedigk A, Dunnenberger HM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) Genotype. Clin Pharmacol Ther. 2012;95(4):376-382. Updated 2014. https://cpicpgx.org/guidelines/guideline-for-codeine-and-cyp2d6/.

4) Dean L. Amitriptyline therapy and CYP2D6 and CYP2C19 genotype. 2017. In: Pratt V, McLeod H, Rubinstein W, et al, editors. Medical Genetics Summaries [Internet]. Bethesda, MD: National Center for Biotechnology Information; 2012. Available from: https://www.ncbi.nlm.nih.gov/books/NBK425165/.

5) 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

The information provided herein and in the pharmacogenetics report is for physician consideration and each physician has to determine  what is the best treatment for their patient based upon the physician’s education, experience, and clinical assessment of the patient.