Despite making significant progress over the last two decades, implementation of pharmacogenomic testing into routine clinical practice is currently limited. Read on to find out more about these tests, their uses, and how they can help to inform drug selection and dosage decisions.
Pharmacogenomics is the study of how gene variants can affect a patient’s response to medication. Pharmacogenomic information has the potential to guide the prescription of medications including avoiding specific drugs in people with a high risk of developing an adverse reaction and/or selecting the optimal dose of a drug.
Pharmacogenomic tests examine genes that may influence an individual’s response to medications. The genes tested are either involved in the absorption, distribution, metabolism or excretion of a medication, pharmacological targets or in the modulation of immune response. For example, variants in the drug metabolizing enzyme CYP2D6 can alter the rate at which a patient metabolises codeine (1) while patients with a variant in the HLA gene complex (HLA-B*58:01) can develop severe adverse reactions to the drug allopurinol.
Research on clinical utility of pharmacogenomic tests has made significant progress over the last two decades (2). Clinicians and members of the public have also expressed positive attitudes to the tests to optimise pharmacotherapy. Despite this, implementation of pharmacogenomic testing into routine clinical practice is currently limited.
Challenges to implementation include the evolving evidence base, cost and turnaround time as well as a lack of education and clinician decision support (3,4). Interpretation of pharmacogenomic information in the clinic is also complex. Although international guidelines on pharmacogenomic testing exist (such as the Clinical Pharmacogenetics Implementation Consortium https://cpicpgx.org/guidelines/), recent Australian College publications (3,4) highlight the “evolving” evidence base and caution against using pharmacogenomic tests in isolation. GPs are encouraged to be “critical users” (5), integrating pharmacogenomic test results with other key factors such as differences in age or size, overall health, and other medications the patient may be taking (3,4).
GPs can order pharmacogenomic test panels or single gene tests from commercial providers within Australia and globally. However, only two single gene tests for adverse drug response are currently listed on the Medicare Benefits Schedule (MBS). The first is for a variant in the TPMT gene due to its effect on metabolism of azathioprine, used to manage cancer, chronic inflammation and immune suppression; the second for the HLA gene complex and anti-retroviral drug abacavir.
There is evidence that pharmacogenomic testing can inform prescribing decisions for many commonly used drugs (5,6). Further, high quality guidelines are available to assist GPs in the clinical interpretation of test results.
As GPs become more knowledgeable, it is anticipated that pharmacogenomic tests will be increasingly used in clinical practice to predict an adverse response, or the optimal dose of a patient’s medication (7). However, more studies are required to evaluate the implementation of these tests -- and how data can be shared among different health professionals - to enhance the clinical utility of this information.
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Variant: An alteration (or change) in your DNA. Most changes do not cause any problems. However, some changes can cause disease – these changes are known as pathogenic variants.
Pharmacogenomics: The study of how a person’s genetic makeup affects their response to medications. Commonly used interchangeably with the term pharmacogenetics.
- Crews, K. R., Gaedigk, A., Dunnenberger, H. M., Leeder, J. S., Klein, T. E., Caudle, K. E., . . . Skaar, T. C. (2014). Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther, 95(4), 376-382. doi:10.1038/clpt.2013.254
- Krebs, K., & Milani, L. (2019). Translating pharmacogenomics into clinical decisions: do not let the perfect be the enemy of the good. Human Genomics, 13(1), 39. doi: 10.1186/s40246-019-0229-z
- The Royal Australian College of General Practitioners (2019. Genomics in general practice. East Melbourne, Vic RACGP. https://www.racgp.org.au/clinical-resources/clinical-guidelines/key-racgp-guidelines/view-all-racgp-guidelines/genomics-in-general-practice
- The Royal College of Pathologists of Australasia (2018). Utilisation of pharmacogenomics in healthcare, 3/2018. https://www.rcpa.edu.au/Library/College-Policies/Position-Statements/Utilisation-of-pharmacogenetics-in-healthcare
- Polasek, T., Mina, K., & Suthers, G. (2019). Pharmacogenomics in general practice. Australian Journal for General Practitioners, 48, 100-105.
- Relling, M. V., & Evans, W. E. (2015). Pharmacogenomics in the clinic. Nature, 526(7573), 343-350. doi:10.1038/nature15817
- Hayward, J., Bishop, M., Rafi, I., & Davison, V. (2017). Genomics in routine clinical care: what does this mean for primary care? British Journal of General Practice, 67(655), 58-59. doi:10.3399/bjgp17X688945
Dr Sophie Stocker PhD, BSc (Hons I)
Dr Sophie Stocker is a Senior Hospital Scientist in the Department of Clinical Pharmacology and Toxicology at St Vincent’s Hospital, Sydney. She is also a conjoint lecturer of the St Vincent’s Clinical School, University of New South Wales. Her research focuses on understanding variability in response to medicines and how this can be managed to optimise patient care.
Ms Bronwyn Terrill BSc, GradDipSciComm, DipEd GradCertAppSci, MEd
Bronwyn is a genomics educator and communicator in the Kinghorn Centre for Clinical Genomics at the Garvan Institute of Medical Research. She collaborates on research exploring the needs of Australia's health workforce in genomic medicine, what makes someone ‘genetically literate’, and public expectations of personal genomic testing.