Pharmacogenetic Testing and Personalised Prescribing

People can respond differently to the same medicine. Pharmacogenetic testing provides insight into how genetic variation may influence medication response, helping doctors and pharmacists consider an appropriate medicine and dose.

Genetic variation may affect how quickly medicines are absorbed, metabolised or transported in the body. These differences can influence efficacy and may also affect the likelihood or severity of side effects.

This article explains what pharmacogenetic testing involves, how genes influence drug metabolism, what a pharmacogenetic profile can show, and how genetic results can support more personalised prescribing.

Key Takeaways: Pharmacogenetic Testing and Personalised Prescribing

• Pharmacogenetics examines how DNA variation may influence an individual's response to a medicine, through enzymes, receptors and transport proteins involved in medication processing.
• A pharmacogenetic profile can show potentially abnormal activity across more than 15 enzymes, transport proteins and receptors, and can indicate a possible abnormal response to more than 50 medicines.
• A genetically predicted result can differ from an individual's real-time metabolic activity because of non-genetic factors — a phenomenon known as phenoconversion — and allele frequencies for genes such as CYP2D6 vary by ancestry.
• Clinical guidelines such as those from CPIC and DPWG are gene–drug pair specific and should be interpreted in context; they are not interchangeable with a general prescribing rule.
• A negative or unremarkable result does not exclude pharmacogenetic risk — it means the tested variants were not identified within the scope of the assay.
• Pharmacogenetic results support clinical decisions but do not replace the judgement of a doctor or pharmacist, and should not be used to independently start, stop or change a medicine.

What Is Pharmacogenetic Testing and Why Does It Matter?

Pharmacogenetics is the scientific study of how variations in DNA relate to an individual's response to a medicine. Pharmacogenetic testing uses this information to identify genetic factors that may affect medication efficacy, metabolism or tolerability.

Genetic variations occur naturally. They may cause a medicine to be processed more slowly or more quickly than average. The result may be a different level of exposure to the medicine or a different response to a standard dose.

What Information Does Pharmacogenetic Testing Provide?

A pharmacogenetic DNA test can provide information about genes involved in drug metabolism, transport and pharmacological response. Laboratory results may be translated into a predicted metaboliser phenotype, such as normal, intermediate, poor or ultrarapid metabolisation, depending on the gene–drug pair and the testing method used.

This information is one part of the clinical picture. It should be considered alongside the medicine, the indication, other medicines, organ function, relevant medical history and the individual's response over time.

A predicted phenotype is not the same as measured enzyme activity at the time a medicine is prescribed. Co-medication, organ function, age and other factors can cause a person's functional metabolic state to differ from their genetically predicted phenotype — this is known as phenoconversion, and it is one reason a genetic result should be interpreted alongside the full clinical picture rather than in isolation.

How Does Pharmacogenetics Support Personalised Medicine?

Traditional prescribing often begins with a standard medicine and dose, followed by adjustment if the expected effect is not achieved or side effects occur. Pharmacogenetic information can provide additional context earlier in the decision process.

The objective is not to generate genetic data for its own sake. The objective is to translate relevant DNA information into a clinically appropriate decision, where the available evidence supports doing so.

How Do Genes Influence Drug Metabolism?

Medicines are processed through interconnected biological pathways. Enzymes, receptors and transport proteins can influence how a medicine is activated, broken down, distributed or eliminated.

Which Enzymes and Transport Proteins Are Involved?

Many medicines are metabolised by enzymes in the liver. CYP2D6, for example, is involved in the metabolism of approximately 20–25% of commonly prescribed medicines. Other important genes include CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, BCHE, DPYD, TPMT and VKORC1.

The relevant pathway varies from one medicine to another. Transport proteins such as SLCO1B1, as well as genes including HLA loci and IFNL3 (formerly known as IL28B), may also contribute to medication response.

Note on IFNL3/IL28B: this gene's main historical clinical use was predicting response to interferon-based hepatitis C treatment. Interferon-containing regimens have been largely superseded by direct-acting antivirals since the mid-2010s, so the clinical actionability of this marker is now limited for most patients being treated for hepatitis C today. It is included here for completeness of the panel, not as a marker with broad current clinical utility.

Why Can the Same Medicine Affect Individuals Differently?

Amitriptyline or codeine, for example, may not be metabolised at the same rate by every individual. Differences in metabolism can influence the amount of active medicine or metabolite available in the body.

Medication response is also influenced by factors beyond inherited genetic variation. Drug–drug interactions, age, organ function, adherence and the underlying condition may all affect the clinical outcome. Allele frequencies for genes such as CYP2D6 also vary meaningfully across populations and ancestries, which can influence how common or expected a given result is.

What Can a Pharmacogenetic Profile Show?

DNA analysis can be used to create a personal pharmacogenetic profile. The profile described here provides an overview of potentially abnormal activity across more than 15 enzymes, transport proteins and receptors.

Which Biological Functions Can Be Assessed?

The profile can provide insight into biological pathways involved in medication processing. This may help clarify why a medicine could be metabolised differently from one individual to another.

The relevance of each result depends on the medicine being considered. A genetic finding may be clinically actionable for one gene–drug pair and have limited or uncertain significance for another. A test also cannot detect every possible relevant variant. Read more in the section "What are the limitations of pharmacogenetic testing?" below.

How Many Medicines Can Be Included?

The profile can indicate whether an individual may have an abnormal response to more than 50 medicines. Only medicines for which an active dosing policy is currently recommended have been included in the profile described here.

Does a Pharmacogenetic Profile Determine the Right Medicine?

A pharmacogenetic profile does not determine a medicine or dose on its own. It adds genetic context to the medication decision, while the appropriate prescribing approach remains dependent on clinical judgement and the individual's circumstances.

How Is Pharmacogenetic Testing Used in Clinical Practice?

The clinical value of pharmacogenetic testing depends on how results are interpreted and integrated into care. A result becomes useful when it can support a specific medication decision and when the evidence for that gene–drug relationship is sufficiently robust.

When Can Pharmacogenetic Results Be Useful?

Pharmacogenetic information may be considered when a medicine has a well-characterised gene–drug interaction, when an individual has experienced an unexpected response, or when a clinician is assessing medication choice or dose.

The timing and relevance of testing vary. Some recommendations concern pre-emptive testing, while others are intended to guide the use of results that are already available.

How Do CPIC and DPWG Guidelines Support Clinical Decisions?

The Clinical Pharmacogenetics Implementation Consortium (CPIC) develops guidelines to help clinicians understand how available genetic test results can be used to optimise drug therapy. CPIC guidance is focused on the interpretation and use of results rather than making a universal recommendation about whether testing should be ordered.

The Dutch Pharmacogenetics Working Group (DPWG) provides evidence-based recommendations for specific gene–drug pairs. Its clinical implication framework distinguishes between testing that may be potentially beneficial, beneficial or essential, depending on the available evidence and expected clinical impact. (This tiering should be confirmed against the current DPWG framework, as terminology has been revised over time.)

There is not a single EU-wide body that plays an identical role to CPIC or DPWG. Instead, the European picture is built from several complementary sources:

• The European Medicines Agency (EMA) does not publish a unified biomarker table equivalent to the FDA's. Pharmacogenomic information for centrally authorised medicines is instead reflected in each medicine's Summary of Product Characteristics (SmPC) and European Public Assessment Report (EPAR), reviewed on a per-medicine basis.
• National competent authorities (for example ANSM in France, BfArM in Germany, AIFA in Italy, AEMPS in Spain) reflect pharmacogenomic information in labelling for nationally authorised medicines.
• The Ubiquitous Pharmacogenomics consortium (U-PGx) and its PREPARE study, an EU-funded, multi-country clinical implementation project, evaluated pre-emptive pharmacogenetic panel testing across seven European healthcare systems (the Netherlands, UK, Spain, Italy, Greece, Austria and Slovenia), building on and extending DPWG's gene–drug pairs into a genuinely pan-European clinical setting.
• Professional societies such as the European Society of Pharmacogenomics and Personalised Therapy (ESPT) work to harmonise pharmacogenomic implementation across European countries.

These guidelines are not interchangeable with a general prescribing rule. Recommendations are specific to the gene, medicine, phenotype, clinical context and, in some cases, the healthcare system under consideration.

Why Should Results Remain Clinician-Led?

Pharmacogenetic results require clinical interpretation. A doctor or pharmacist can assess whether a finding is relevant to the medicine being considered, review other clinical factors and determine whether an adapted prescribing approach is appropriate.

This distinction matters. A genetic result can support a decision, but it does not replace the broader assessment required for safe and effective medication use.

What does this mean in clinical practice?

Taken together, the evidence supports a specific and bounded clinical role for pharmacogenetic testing: for gene–drug pairs with well-characterised, guideline-supported associations (such as CYP2D6/CYP2C19 with selected antidepressants and opioids, DPYD with fluoropyrimidines, or SLCO1B1 with statins), a predicted phenotype can meaningfully inform medicine or dose selection alongside standard clinical assessment.

This is different from claiming that pharmacogenetic testing predicts an individual's response to any medicine, or that it should replace standard clinical monitoring. Its clinical value comes from being integrated into an existing prescribing decision by a qualified professional — not from being read as a standalone result.

What Are the Limitations and evidence boundaries of Pharmacogenetic Testing?

Pharmacogenetic testing can provide clinically relevant information, but it does not explain every difference in medication response. The strength of the conclusion depends on the gene–drug pair, the quality of the evidence and the scope of the test.

Can a Test Detect Every Relevant Genetic Variant?

No genetic test detects every possible variant. Targeted genotyping typically examines selected variants that have already been characterised. Rare variants, structural variants or variants outside the tested panel may not be identified.

For this reason, the specific variants included in the assay and the method used to translate genotype into predicted phenotype should be understood when results are interpreted.

Does a negative or unremarkable result exclude pharmacogenetic risk?

No. A negative or unremarkable result means the tested variants were not identified within the scope and limits of the assay. It does not exclude untested variants, structural changes, non-genetic interactions, or a gene–drug relationship not included in the panel.

Do genetic results predict a certain clinical outcome?

Genetic results may indicate an increased likelihood of a particular medication response. They do not guarantee efficacy, toxicity or a specific clinical outcome.

Claims should remain proportionate to evidence. The clinical question is not simply whether genetic variation is present, but whether the result is sufficiently relevant and actionable for the medicine and individual being considered.

FAQs About Pharmacogenetic Testing

What Is Pharmacogenetic Testing?

Pharmacogenetic testing analyses selected genetic variants that may influence how an individual responds to certain medicines. Results can provide information about drug metabolism, transport or pharmacological response.

What Is the Difference Between Pharmacogenetics and Pharmacogenomics?

Pharmacogenetics generally refers to the relationship between individual genetic variation and medication response. Pharmacogenomics is often used more broadly to describe the study of how the genome influences drug response. In clinical communication, the terms may overlap.

Can Pharmacogenetic Testing Show Whether a Medicine Will Work?

It may provide evidence about the likelihood of a particular response for a specific gene–drug pair. It cannot guarantee efficacy or predict every clinical outcome, and results must be interpreted alongside other patient and medication factors.

How Many Medicines Can the Profile Assess?

The pharmacogenetic profile described here can indicate whether an individual may have an abnormal response to more than 50 medicines. It also provides an overview of potentially abnormal activity across more than 15 enzymes, transport proteins and receptors.

Does a Pharmacogenetic Profile Replace a Doctor or Pharmacist?

No. The profile provides additional information for clinical decision-making. A doctor or pharmacist must interpret the results in the context of the medicine, the individual's clinical circumstances and the available evidence.

What is phenoconversion?

Phenoconversion is a difference between genetically predicted enzyme activity and an individual's actual, observed activity, caused by non-genetic factors such as enzyme inhibitors, inducers, organ function or age. It means a genetic result may not fully describe functional metabolism at the time of treatment.

Does interpretation differ by ancestry?

Allele definitions are consistent across populations, but allele frequencies are not. For CYP2D6 and some other pharmacogenes, certain functionally important alleles are more common in some ancestries than others, which can affect how a result should be interpreted.

What do CPIC, DPWG and other European sources contribute?

CPIC guidelines help clinicians use available genetic test results to optimise drug therapy. DPWG recommendations provide evidence-based guidance for specific gene–drug pairs and assess the potential clinical value of pre-emptive genotyping. Because no single EU-wide body plays an identical role, EMA product labelling, national competent authorities, and pan-European implementation research such as the U-PGx/PREPARE study also contribute to the European evidence picture. These sources should be applied within the relevant clinical context, and their frameworks are not interchangeable with each other or with a general prescribing rule.

Scientific references

Ordered per BioAgeDiagnostics SOP §2 (regulatory/governmental authorities → clinical guidelines → peer-reviewed literature → mechanistic/educational → commercial).

Links are provided from training knowledge and have not been live-verified in this session — confirm each before publication (SOP §18).

1. Regulatory and governmental scientific authorities

• U.S. Food and Drug Administration. Table of Pharmacogenomic Biomarkers in Drug Labeling. https://www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling
• European Medicines Agency. Medicines — Summary of Product Characteristics and European Public Assessment Reports (per medicine). https://www.ema.europa.eu/en/medicines (EMA does not publish a single unified pharmacogenomic biomarker table; pharmacogenomic information is reviewed per medicine within SmPC/EPAR documentation.)
• European Medicines Agency. Pharmacogenomics — scientific guidelines. https://www.ema.europa.eu/en/human-regulatory-overview/research-development/scientific-guidelines/pharmacogenomics (URL to be confirmed — EMA has reorganised this content in the past.)
• National competent authorities, where nationally authorised products are relevant (e.g. ANSM, France; BfArM, Germany; AIFA, Italy; AEMPS, Spain) — cite the specific medicine's national labelling where used to support a claim.

2. Scientific and clinical guidelines

• Clinical Pharmacogenetics Implementation Consortium (CPIC). Guidelines. https://cpicpgx.org/guidelines/
• CPIC. Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4 and HTR2A genotypes and select serotonin reuptake inhibitor antidepressants (2023 update). Via CPIC guidelines page above — confirm exact guideline URL slug before publication.
• CPIC. Guideline for CYP2D6, OPRM1 and COMT genotypes and select opioid therapy. Via CPIC guidelines page above.
• Dutch Pharmacogenetics Working Group (DPWG). Guidelines accessed via ClinPGx: https://www.clinpgx.org/page/dpwg
• Swen JJ, et al. (DPWG). Dutch Pharmacogenetics Working Group guideline for the CYP2D6 and opioid gene–drug interaction. European Journal of Human Genetics. DOI/URL to be confirmed prior to publication.
• Ubiquitous Pharmacogenomics consortium (U-PGx). Project overview. https://upgx.eu/ (URL to be confirmed.)
• Swen JJ, et al. A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study (PREPARE study, U-PGx consortium). The Lancet. 2023. DOI/URL to be confirmed prior to publication.
• European Society of Pharmacogenomics and Personalised Therapy (ESPT). https://www.esptnet.eu/ (URL to be confirmed.)
• ClinPGx (formerly PharmGKB). Gene-specific information, CYP2D6. https://www.clinpgx.org/gene/PA128
• PharmVar. CYP2D6 allele nomenclature. https://www.pharmvar.org/gene/CYP2D6

3. Peer-reviewed scientific literature

• Caudle KE, et al. Standardizing CYP2D6 genotype to phenotype translation: consensus recommendations from the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group. Clinical and Translational Science. DOI/URL to be confirmed prior to publication.
• (Additional systematic reviews/meta-analyses on specific gene–drug pairs referenced in this article should be added here with full citation detail before publication.)

4. Mechanistic and preclinical literature

• Not applicable to this article — all pharmacogenetic mechanisms described are supported by the clinical guidelines cited above rather than preclinical-only evidence.

5. Reputable scientific/medical educational sources

• NHS Genomics Education Programme. Pharmacogenomics of CYP2D6. https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/cyp2d6/
• UK Clinical Pharmacy Association. Handbook of Pharmacogenomics. URL to be confirmed prior to publication.

6. Commercial sources

• None used. Per SOP §2, commercial sources are used only when primary or authoritative sources are unavailable; none were required for this article.

Medical disclaimer

This article is for educational purposes only and does not provide individual medical or prescribing advice. Pharmacogenetic results should be interpreted by an appropriately qualified healthcare professional in the context of the specific medicine, current prescribing guidance and relevant patient-specific factors. Medicines should not be started, stopped or changed on the basis of genetic test results without professional medical guidance.