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Pharmacogenomics in general practice

Despite potential savings of more than $1 billion annually, awareness of pharmacogenomic tests among Australian prescribers is low and national guidelines for their use have not been developed. This void contributes directly to the continued prescribing of ineffective medications, unacceptably high rates of adverse drug reactions and associated personal and economic costs.

Pharmacogenomics (PGx) is the study of how the genome of an individual patient influences their response to a medication.

Pharmacogenomic testing, by aligning a given medication (and its dosing) to an individual’s genetic potential for therapeutic or adverse response, adds a further dimension to the concept of personalised medicine.

The efficacy and safety of a medication, which must be established prior to its release and marketing, is currently assessed by clinical trials involving thousands of individuals. The broadly applicable conclusions derived from this process have formed the evidence-base for prescribing over many decades but are antithetical to a clinical paradigm which is becoming increasingly personalised.

Pharmacogenomic testing provides the means whereby prescribing is no longer tied to population-derived norms but can be tailored to an individual’s genotype.

The underlying principle is that genetic variation determines how much medication an individual patient will have in their body (that is, plasma concentration, sometimes called ‘exposure’) and whether they are at high risk of certain toxicities.

The continual identification of genetic variants associated with higher or lower plasma concentrations, and the increasing availability and falling cost of the technology involved in doing so, is realising the potential to personalise medicine and dose selection, maximising benefit and minimising harm as a consequence.

Those who will respond to a medication and those who will have to stop treatment because of toxicity can be identified before money is wasted or toxicity develops.

Pharmacogenomics provides only one type of information which can be used to explain a medication-related problem (that is, no response or toxicity) or to determine whether one medication might be more suitable for a patient compared to another, but the information it provides should not be used as the sole basis for prescribing decisions.

Pharmacogenomic information should be considered together with relevant clinical information, such as age, renal and liver function, medication history, concurrent medications and level of patient understanding, prior to prescribing.

Pharmacogenomics does not replace clinical assessment, other pathology or therapeutic drug monitoring. The information it provides informs, but does not replace, clinical judgement.

Case studies

Antidepressant therapy

A GP was caring for a woman aged 55 years, with a history of anxiety and depression and no other medical problems. The patient was managed by a psychologist for many years.

After the patient lost her job, her mood deteriorated, she spent most days in bed, and motivation for finding new work was poor. The decision was made to commence medication, prescribing sertraline titrated to 200mg daily, the highest recommended dose.

Several months of treatment failed to help, and sertraline was then swapped for citalopram. The patient deteriorated further and then required a psychiatric admission approximately six months after her initial clinical decline.

Prior to hospitalisation, the GP ordered pharmacogenomic tests. The results showed low exposure to sertraline and citalopram, due to high CYP2C19 activity (CYP2C19*17/*17), leading to rapid metabolism of these antidepressants.1 This information was forwarded to the treating psychiatry team.

Venlafaxine was chosen as an alternative antidepressant because exposure is not as dependent on CYP2C19, and the patient recovered and came off medication 12 months later.

Statin therapy

A fit man visited his GP after turning 50 years of age, for his first health check in years. He brought to the appointment the results of pharmacogenomic tests performed via the local pharmacy.

The tests were taken because his parents had both had heart attacks and his wife thought the tests could predict ‘heart trouble’.

The health check results were normal, except for a total cholesterol of 7.8mmol/L. The decision was made to start a statin. The GP remembered seeing something about statins in the pharmacogenomic report, and subsequently, the report was considered in more detail at the follow-up appointment. The patient had low activity of the main transporter responsible for taking simvastatin and atorvastatin into the liver (SLCO1B1*5/*17), a result associated with higher exposure to simvastatin and higher rates of statin-associated muscle toxicity, compared with other genetic variants.3 Rosuvastatin exposure is less pronounced in patients with this genotype, and so it was chosen rather than simvastatin or atorvastatin.

The evidence for pharmacogenomics

Although there is still much work to determine the real potential of pharmacogenomics, there is already a large body of peer-reviewed clinical evidence that has been collated, assessed, and then developed into prescribing guidelines by international expert bodies, for example, the US-based Clinical Pharmacogenomics Implementation Consortium (CPIC) and the European-focused Dutch Pharmacogenomics Working Group (DPWG).

Independent Australasian guidelines are lacking at the moment, but providers of commercial pharmacogenomic tests give prescribing advice based on these International guidelines.

As an indication of the potential relevance of pharmacogenomics in the Australian setting, a recent study of approximately 5,400 Australians showed that 96% had at least one clinically actionable pharmacogenomic variant.4

Optimise prescribing with the Sonic Pharmacogenomics Panel

The Sonic PGx Panel is a pharmacogenomic test which is now available at Douglass Hanly Moir Pathology (through Sonic Genetics).

Based on the detection (or not) of defined genotypic variants, the report provides evidence-based, clinically relevant guidance concerning medication selection and dosing across a range of important therapeutic areas, including cardiology, gastroenterology, pain management, and psychiatry and addiction medicine.

The guidance provided is specific to the patient’s genotype and can be used as an adjunct to the information provided by clinical assessment and examination, medication history and results of other laboratory investigations.

Genomics has potential application in many areas, including pharmacotherapy.

By providing a rational basis for medication selection based on the reliable expectation of optimum therapeutic response and absence of adverse reactions, pharmacogenomics represents an important advance in the development of personalised medicine.



  1. Ramsey LB, Johnson SG, Caudle KE, Haidar CE, Voora D, Wilke RA, et al. The Clinical Pharmacogenetics Implementation Consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clin Pharmacol Ther. 2014 Oct; 96(4): 423-8. DOI: 10.1038/clpt.2014.125
  2. Hicks JK, Bishop JR, Sangkuhl K, Müller DJ, Ji Y, Leckband SG, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015 Aug; 98(2): 127-34. DOI: 10.1002/cpt.147
  3. Johnson JA, Caudle KE, Gong L, Whirl-Carrillo M, Stein CM, Scott SA, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for pharmacogenetics-guided warfarin dosing: 2017 update. Clin Pharmacol Ther. 2017 Sep; 102(3): 397-404. DOI: 10.1002/cpt.668
  4. Mostafa S, Kirkpatrick CMJ, 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 (Vienna). 2019 Jan; 126(1): 5-18. DOI: 10.1007/s00702-018-1922-0

General Practice Pathology is a regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.