Pharmacogenomics: Transforming Prescribing Practices for Personalised Medicine

Did you know that approximately 5-8% of hospital admissions are medication-related, with many being potentially preventable? Even more concerning, this figure rises to over 13% in patients aged 65 and older. In England alone, the NHS dispenses over 1 billion prescription drugs annually—a 50% increase from just 15 years ago. Yet despite this volume, there's a fundamental issue: medications don't work the same way for everyone.

The reason? Our genes. Welcome to the world of pharmacogenomics (PGx)—where your DNA meets your medicine cabinet, offering a revolutionary approach to prescribing that promises more effective treatments, fewer adverse reactions, and better patient outcomes.

What is Pharmacogenomics?

Pharmacogenomics studies how an individual's genetic makeup influences their response to medications. It integrates the science of drugs (pharmacology) with the study of genes and their functions (genomics) to develop and prescribe medications tailored to a person's genetic profile.

Our DNA contains natural variations that affect how our bodies process medications through two primary mechanisms:

1. Pharmacokinetics: How the body absorbs, metabolises, distributes, and excretes drugs
2. Pharmacodynamics: How drugs affect the body, including interactions with target receptors, enzymes, and ion channels

Over 98% of individuals carry at least one pharmacogenetic variant that could impact their medication response. These variations can determine whether a medication will be effective, ineffective, or even harmful for a specific person.

Consider this real-world example: Codeine must be metabolised by the liver enzyme CYP2D6 to produce its active form, morphine, which provides pain relief. People with CYP2D6 "poor metaboliser" variants cannot effectively convert codeine to morphine, resulting in little to no pain relief. Meanwhile, those with "ultra-rapid metaboliser" variants convert codeine too quickly, potentially leading to dangerous morphine levels and serious adverse effects.

My Experience of Genomic Medicine

My inspiration for this article came from a fascinating presentation at the Primary Healthcare Specialist Group Conference (2024), which I had the privilege of helping organise. The session, delivered by Dr. Jude Hayward, Primary Care Lead for the National Genomics Education Programme, and Dr. Videha Sharma, Clinical Innovation Lead at the Pankhurst Institute, showcased the transformative potential of pharmacogenomics in primary care.

Their presentation on implementing pharmacogenomics through an informatics approach highlighted not just the scientific advancements in this field, but the practical pathways to bringing this technology into everyday clinical practice. What struck me most was how close we are to making personalised prescribing a reality for patients across the UK, and the profound impact this could have on healthcare outcomes.

Current Applications in Healthcare

Pharmacogenomic testing already benefits patients in several key areas:

Cancer Treatment: In breast and colorectal cancer treatment, PGx testing identifies whether patients can safely receive fluoropyrimidine therapies like 5-fluorouracil. By testing for DPYD gene variants before treatment, clinicians can identify patients at risk for severe toxicity and adjust dosing accordingly.

HIV Treatment: Testing for the HLA-B*57:01 gene variant before prescribing abacavir has become standard practice. This test completely eliminates immunologically confirmed abacavir hypersensitivity syndrome, which previously affected 5-7% of patients receiving this medication.

Preventing Adverse Drug Reactions: Testing for HLA-B*15:02 in patients of Southeast Asian descent before prescribing carbamazepine (an anticonvulsant) can prevent Stevens-Johnson syndrome, a rare but potentially fatal skin reaction.

Primary Care Impact: 58% of patients in primary care settings receive at least one medication influenced by PGx factors, with this figure rising to 89% in patients over 70 years old. The most frequently prescribed PGx-relevant medications address pain management, gastrointestinal protection, psychiatric conditions, and cardiovascular disease.

The UK's Leadership in Genomic Medicine

The UK stands at the forefront of the genomic revolution. Following the groundbreaking 100,000 Genomes Project, the NHS Genomic Medicine Service was established in 2018 to integrate research, education, and diagnostic resources for bringing genomic medicine—including pharmacogenomics—into routine clinical care.

In 2018, the UK government announced plans to sequence five million genomes in five years. The NHS currently offers whole-genome analysis to seriously ill children with suspected genetic disorders and adult patients with certain rare diseases or difficult-to-treat cancers.

A major milestone was reached in 2020 when the NHS commissioned genomic testing for DPYD variants as a pre-treatment screening test before administering fluoropyrimidine-based therapies, marking the first nationwide implementation of a pharmacogenomic test.

Benefits of Pharmacogenomic Implementation

The potential advantages of integrating PGx into routine healthcare are substantial:

1. Reducing Adverse Drug Reactions: The PREPARE trial demonstrated a 30% reduction in adverse drug reactions when using PGx-guided prescribing. Given that avoidable adverse drug reactions cost the NHS £530 million annually in hospital admissions, this represents significant potential savings.
2. Improving Treatment Efficacy: Multiple randomised clinical trials have shown that patients receiving PGx-guided dosing for depression treatment are 1.71 times more likely to achieve symptom remission compared to standard care.
3. One-Time Testing, Lifetime Benefits: Unlike other medical tests that must be repeated regularly, germline pharmacogenomic testing typically needs to be performed only once, with results remaining valid throughout a patient's lifetime to guide multiple prescribing decisions.
4. Personalised Approach to Polypharmacy: As populations age and more people live with multiple conditions, pharmacogenomics offers particular benefits for managing complex medication regimens, potentially reducing polypharmacy risks.

Challenges to Implementation

Despite its promise, several barriers currently limit widespread PGx adoption:

Education and Training Gaps: A review of healthcare curricula revealed that pharmacogenomics is not universally included in pre-registration education. This creates a knowledge gap among healthcare professionals.

Technical Integration: Pharmacogenomic data will have to be integrated with a number of different electronic health systems used in hospitals and community clinics.

Service Design: Questions remain about the optimal approach to testing—whether to check pre-emptively for panels of pharmacogenes or only test variants of interest, and whether testing should occur before prescribing or after adverse events.

Funding and Resource Allocation: Implementing a national, equitable pharmacogenomics service requires appropriate funding and resource allocation, particularly challenging in the wake of the COVID-19 pandemic and stretched public finances.

The Path Forward

To successfully implement pharmacogenomics across the NHS, experts recommend several key strategies:

1. Nationwide, Equitable Implementation: PGx services should be commissioned and funded through relevant national pathways rather than being locally driven, to avoid creating a "postcode lottery" of care that could exacerbate inequalities.
2. Comprehensive Education: A layered approach to education should be available so healthcare professionals can access "just-in-time" information, short courses, or formal qualifications based on their needs and roles.
3. Clinical Decision Support: Systems should be developed to make PGx information available at the point of prescribing and easy to interpret—comparable to drug allergy record flags—to influence real-time clinical decisions.
4. Multidisciplinary Support: Healthcare systems will require a team of clinicians, pharmacists, clinical pharmacologists to implement and support healthcare providers
5. Continuous Evaluation: Services should be subject to continuous audit, research, and patient feedback to develop a learning health system that allows continual improvement.

What This Means for You

For Healthcare Professionals:

• Stay informed about developments in PGx through continuing professional development
• Consider PGx factors when prescribing medications known to have significant genetic influences
• Advocate for PGx testing integration into your clinical setting
• Familiarise yourself with available PGx resources and guidelines from organisations like CPIC

For Patients and Health-Conscious Individuals:

• Be aware that genetic factors may influence your response to medications
• Discuss with your healthcare provider whether PGx testing might be beneficial, particularly if you've experienced unusual medication responses
• Understand that PGx is just one factor in medication response—age, other medications, and health conditions also play important roles
• Keep records of any adverse medication reactions to share with healthcare providers

Conclusion

Pharmacogenomics represents a significant step toward truly personalised medicine, with the potential to transform prescribing practices from a "one-size-fits-all" approach to individualised treatment plans based on genetic profiles. The UK's leadership in genomic medicine positions the NHS to potentially become the first healthcare system to fully integrate pharmacogenomics nationwide.

While challenges remain, the evidence supporting the clinical utility and cost-effectiveness of PGx continues to grow. As implementation advances, we can anticipate a future where medications are routinely prescribed according to genetic profiles, leading to more effective treatments, fewer adverse reactions, and better patient outcomes.

The journey toward personalised prescribing has begun—and pharmacogenomics is leading the way.

References

1. Royal College of Physicians and British Pharmacological Society. Personalised prescribing: using pharmacogenomics to improve patient outcomes. Report of a working party. London: RCP and BPS, 2022.
2. Hayward J, Sharma V. Implementing Pharmacogenetics into Primary Care: An Informatics Approach. Primary Care Lead, National Genomics Education Programme, 2024.
3. Rollinson V, Turner R, Pirmohamed M. Pharmacogenomics for Primary Care: An Overview. Genes. 2020;11(11):1337. doi:10.3390/genes11111337
4. Pirmohamed M, Turner R, Magavern E, et al. Personalised prescribing: using pharmacogenomics to improve patient outcomes. Clin Med (Lond). 2022;22(4):337-342. doi:10.7861/clinmed.2022-0189
5. NHS England. NHS Genomic Medicine Service. https://www.england.nhs.uk/genomics/nhs-genomic-med-service/ (Accessed May 2025)
6. Clinical Pharmacogenetics Implementation Consortium (CPIC). Guidelines. https://cpicpgx.org/guidelines/ (Accessed May 2025)
7. Genomics England. The 100,000 Genomes Project. https://www.genomicsengland.co.uk/about-genomics-england/the-100000-genomes-project (Accessed May 2025)