What is Pharmacogenomics (PGx) testing?

Pharmacogenomic (PGx) Testing: Personalized Medication Management

Pharmacogenomic testing examines genetic variants associated with individual variability in drug metabolism to predict drug response phenotypes and guide medication management, improving therapeutic outcomes and reducing adverse events. 1

Definition and Purpose

• PGx testing interrogates germline sequence variants implicated in interindividual drug response variability to infer drug response phenotypes and guide medication management for specific drugs. 1
• The goal is to examine genetic variants associated with variability in pharmacology aspects such as drug metabolism, which can explain therapeutic failures, side effects, adverse events, and nonstandard dosing requirements. 1
• PGx is unique compared to inherited disease genetics because drug response phenotypes are often drug-dependent and may remain unrecognized until an unexpected drug reaction occurs or a patient fails to respond to medication. 1

Clinical Applications

• Approximately 90-95% of individuals have at least one actionable genotype for pharmacogenes, making it highly likely that patients would benefit from personalized medication selection. 2
• PGx testing can pre-emptively guide drug selection and/or dosing decisions for medications with FDA drug labels or professional society therapeutic recommendations. 1, 2
• The identification of certain pharmacogenomic variants may indicate that a patient should avoid specific medications due to efficacy concerns or risk of serious side effects. 1
• PGx testing can suggest when a patient may benefit from nonstandard medication doses, contributing to personalized or precision medicine approaches. 1, 3

Commonly Tested Genes and Biomarkers

• PGx tests commonly examine genes involved in pharmacokinetic (drug inactivation or activation) or pharmacodynamic (drug response) pathways. 1
• Common pharmacogenomic biomarkers include enzymes, receptors, ion channels, transporter proteins, and immune mediators. 1, 4
• Examples include CYP2C9 and VKORC1 variants that affect warfarin metabolism and dosing requirements. 5
• Many clinical PGx tests target multiple genes simultaneously, with some tests examining 20+ genes and dozens of SNPs (Single Nucleotide Polymorphisms). 3, 4

Implementation and Resources

• Several resources support clinical pharmacogenomic testing, including:
  • The Pharmacogenomic Knowledgebase (PharmGKB) - repository for gene-drug associations and dosing guidelines 1
  • The Clinical Pharmacogenetics Implementation Consortium (CPIC) - creates evidence-based gene/drug clinical practice guidelines 1
  • The Pharmacogene Variation (PharmVar) Consortium - catalogs variation data of pharmacogenes 1
• Implementation challenges include turning complex genetic information into actionable recommendations that clinicians can effectively utilize. 3, 6
• Results are typically integrated into electronic health records with clinical decision support tools to provide genotype-guided dosing at the point of care. 4, 7

Benefits and Limitations

• Benefits include:
  • More precise medication selection and dosing 2
  • Reduced risk of adverse drug reactions 3, 8
  • Decreased trial-and-error approach to medication management 2, 6
• Limitations include:
  • Not all medications have sufficient evidence for PGx-guided prescribing 2
  • PGx testing should guide but not be the sole determinant of treatment decisions 2
  • Implementation barriers in primary care settings despite evidence of utility 7

Clinical Areas with Strong Evidence

• PGx testing has particularly strong evidence in:
  • Psychiatry (antidepressants) 8, 7
  • Pain management (codeine, tramadol) 7
  • Cardiovascular medications (warfarin, clopidogrel, statins) 5, 7
  • Other commonly prescribed medications in primary care 6, 7