The right drug, at the right dose, from the start
Studies from Europe have found that approximately 20% of ambulatory patients experience adverse drug reactions (ADRs) and 15-20% of inpatients will have at least one ADR during their hospital stay, as may around 8% of the general population (Taché et al 2011, Ann Pharmacother 45:977-89; Miguel et al 2012, Pharmacoepidemiol Drug Saf, 21: 1139-1154; Hakkarainen et al 2013, PLoS ONE, (8), 9, e73166). ADRs and/or reduced efficacy can lead to patients undergoing the “trial-and-error approach”, adjusting dosages and/or switching medications several times. Patients who undergo this process frequently display poor adherence to treatments and are more likely to discontinue therapies (Palumbo et al, J Clin Psychopharmacol 2024;44: 49–56).
In addition the healthcare costs of ADRs have been shown to be significant, for example in the UK and Germany (respectively 700 million euro and 435 million euro per annum) (Cosgrave et al 2025, Age Ageing 54(8):afaf231).
Pharmacogenetics (PGx) provides a tool to support prescribers in finding the most appropriate treatment by examining the individual genetic profile of the patient, identifying significant pharmacogenetic variants and personalising the choice and dosage of drugs to increase the likelihood of successful therapy and reduce the risk of adverse drug reactions.
PHARMACOGENETIC (PGx) TESTING
Over 95% of people have genetic variations affecting proteins involved in drug activation, transport and elimination. Some of these variations have little clinical effect, but in other cases they can be very important: for example, common genetic variants explain 42% of individual differences in antidepressant response including both lack of efficacy and adverse effects (Tansey et al, Biol Psychiatry 2013 73(7):679-82).
Most of this genetic variation is due to single-nucleotide variants (SNVs, formerly known as single-nucleotide polymorphisms or SNPs). The genes and variants to be analysed are selected based on medical evidence of utility, expert recommendations and publications from professional groups including CPIC, DPWG, EMA, FDA and others. It is fair to say that pharmacogenetics is the genetics of ADMET: the study of variants affecting how drugs are Absorbed, Distributed, Metabolised and Excreted, as well as their eventual Toxicity. The most common pharmacogenetically significant genes are those coding for cytochrome enzymes (CYP) involved in drug metabolism, phase II enzymes involved in drug conjugation before excretion, and proteins transporting drugs into or out of hepatocytes or target organs.
PGx testing is typically performed from a blood sample, or in some cases a cheek swab or a dried blood spot. The genetic analysis can be performed by multiple techniques including PCR, NGS (next-generation sequencing) and SNP array. Once the genotypes have been determined, the phenotype of each target enzyme or transporter is predicted based on published tables, allowing in turn the classification of the likely response to individual drugs and, if reliable published data is available, recommendations of how to personalize drug prescription to improve efficacy and/or reduce adverse effects.
Three general types of PGx tests are available:
- highly-targeted, guideline-based companion diagnostic testing for specific gene-drug interactions, often appearing as label annotations;
- specialised panels for particular medical disciplines, for example for psychiatry, cardiology or gastroenterology;
- broad pre-emptive panels, commonly analysing 10s-100s of genetic variants in 10-50 pharmacogenes.
For more information, please contact genetics@synlab.com.
TARGETED GENE-DRUG PAIRS
GUIDELINE-BASED PHARMACOGENETIC MARKERS
- 5-fluorouracil → DPYD
- Irinotecan → UGT1A1
- Azathioprine → TPMT + NUDT15
- Clopidogrel → CYP2C19
- Warfarin → VKORC + CYP2C9
- Mavacamten → CYP2C19
- Statins → SLCO1B1
- Siponimod → CYP2C9
- Carbamazepine → HLA-B*15:02
MULTIGENE PANELS
PRE-EMPTIVE AND SPECIALTY-SPECIFIC PANELS
SYNLAB myPGx:
- Multidisciplinary pre-emptive panel
- Over 300 prescription drugs across multiple disciplines
myPGx Specialised panels
- Psychiatry | myPGx PSY
- Cardiology | myPGx CARDIO
- Gastroenterology | myPGx GASTRO
- Rheumatology and pain | myPGx RHEUMA