24 November 2020

Pharmacogenomics is coming to general practice

Genetics Pharmacy

Pharmacogenomics is the study of genetic differences that affect an individual’s medication response and metabolism1.

Genetic variation in these processes can cause a patient to have an unexpected exposure to a medication, such as

  • unexpectedly low or high blood concentrations (despite the patient having the recommended dose)
  • unexpected lack of or excessive response to a medication (despite the blood concentration being normal)
  • severe acute reaction e.g. skin rash, hepatitis (despite the medication typically being well-tolerated).

By knowing the variations in a patient’s genes, the prescriber can select a medication and dose that is most likely to be effective and least likely to result in adverse side effects. Clinical trials have confirmed that pharmacogenomic testing can both improve positive health outcomes and avoid negative ones2–5 while being cost-saving6. The avoidance of negative outcomes would, of itself, represent a significant saving for the Australian healthcare system as adverse medication reactions are implicated in approximately 3% of hospital admissions in Australia7.

International authorities have identified 15 genes that have the highest level of evidence for guiding the prescribing of 30 common medications. There are hundreds of other medication-gene combinations for which evidence of the utility of testing is growing (www.pharmgkb.org).

In 2017, these 30 medications were dispensed to approximately 1.7 million patients in Australia. The top 10 medications included simvastatin, codeine, tramadol, clopidogrel, escitalopram, warfarin, amitriptyline, citalopram, allopurinol, and paroxetine. A recent study of 5,400 Australians who were tested for four genes showed that 96% had at least one clinically actionable pharmacogenomic variant8.

The prevalence of common medications and the frequency of variants that place a patient at risk of an adverse outcome hint at the potential significance of pharmacogenomics in Australian clinical practice, as recently reviewed in Australian Prescriber9. For example, the pharmacological management of depression is challenging, with only 50% of patients responding to their initial medication and less than 50% achieving remission within 12 months10.

Two genes, CYP2D6 and CYP2C19, are primarily responsible for the metabolism of many psychotropic medications. Approximately one in six people have variations in CYP2D6 that slow metabolism, while one in three have variants in CYP2C19 that accelerate metabolism. Multiple clinical trials have now demonstrated that testing of these genes is relevant for prescribing2,11, with tangible benefits for patients and funders of care.

There is a comparative dearth of pharmacogenomics in clinical practice in Australia. In contrast to the FDA’s inclusion of pharmacogenomic information on 15% of medication labels in the US1, there is no such requirement by Australian authorities. There is a lack of awareness of pharmacogenomics among local prescribers, few national guidelines regarding pharmacogenomic, and limited Medicare funding (the exceptions being items for genetic testing of TPMT and HLA-B*5701).

The integration of a patient’s history, pharmacogenomic test result, other medications, and therapeutic medication levels remains a matter of clinical judgement. Pharmacogenomics should not be the sole arbiter of prescribing decisions. It should be requested by a healthcare professional with both the knowledge and accountability that is appropriate for the patient’s care. A number of providers now assist prescribers who are new to pharmacogenomic testing by offering tests that have authoritative clinician-friendly interpretations, at a cost to the patient of $150-$250.

Sonic Genetics provides pharmacogenomic testing through Sonic laboratories across Australia (sonicgenetics.com.au).

This piece was originally published at Healthed.com.au as part of an educational initiative developed and coordinated by Sonic Pathology.


1Relling, M. V & Evans, W. E. Pharmacogenomics in the clinic. Nature 526, 343–350 (2015).

2Elliott, L. S. et al. Clinical impact of pharmacogenetic profiling with a clinical decision support tool in polypharmacy home health patients: A prospective pilot randomized controlled trial. PLoS One 12, e0170905 (2017).

3Benitez, J., Jablonski, M. R., Allen, J. D. & Winner, J. G. The clinical validity and utility of combinatorial pharmacogenomics: Enhancing patient outcomes. Appl. Transl. genomics 5, 47–9 (2015).

4Bousman, C. A. et al. Concordance between actual and pharmacogenetic predicted desvenlafaxine dose needed to achieve remission in major depressive disorder?: a 10-week open-label study. 1–6 doi:10.1097/FPC.0000000000000253

5Wang, Z.-Q. et al. Pharmacogenetics-based warfarin dosing algorithm decreases time to stable anticoagulation and the risk of major hemorrhage: an updated meta-analysis of randomized controlled trials. J. Cardiovasc. Pharmacol. 65, 364–370 (2015).

6Plumpton, C. O., Roberts, D., Pirmohamed, M. & Hughes, D. A. A Systematic Review of Economic Evaluations of Pharmacogenetic Testing for Prevention of Adverse Drug Reactions. Pharmacoeconomics 34, 771–793 (2016).

7Improving the Quality Use of Medicines in Australia: Realising the potential of pharmacogenomics. (2008).

8Mostafa, S., Kirkpatrick, C. M. J., Byron, K. & Sheffield, L. An analysis of allele, genotype and phenotype frequencies, actionable pharmacogenomic (PGx) variants and phenoconversion in 5408 Australian patients genotyped for CYP2D6, CYP2C19, CYP2C9 and VKORC1 genes. J. Neural Transm. (2018). doi:10.1007/s00702-018-1922-0

9Somogyi, A. & Phillips, E. Genomic testing as a tool to optimise drug therapy. Aust. Prescr. 40, 101–104 (2017).

10Keks, N., Hope, J. & Keogh, S. Switching and stopping antidepressants. Aust. Prescr. 39, 76–83 (2016).

11Pérez, V. et al. Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: Results of a randomized, double-blind clinical trial. BMC Psychiatry 17, 1–13 (2017).

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