How AI Brings Pharmacogenetics to the Front Line of Precision Medicine

A man aged 55 years with metastatic colorectal cancer was initiated on a standard fluoropyrimidine-based chemotherapy regimen. Within a week, he developed severe neutropenia, gastrointestinal shutdown, and septic complications requiring admission to the intensive care unit. Genetic testing, prompted by a clinical pharmacist’s suspicion of dihydropyrimidine dehydrogenase (DPD) deficiency, revealed a DPYD gene variant that impaired 5-fluorouracil (5-FU) metabolism.

Upon confirmation, the treatment team rapidly transitioned the patient to alternative therapy and administered uridine triacetate as a rescue agent. That single gene—and one pharmacist’s intervention—made the difference between near-death and recovery.¹

This case exemplifies the transformative impact of pharmacogenetic testing in mitigating life-threatening toxicity and guiding alternative, equally effective treatment strategies tailored to the patient’s unique genetic profile.

The Pivotal Role of Pharmacists in Precision Medicine

Pharmacists are uniquely positioned to interpret and apply pharmacogenetic data to improve medication safety and efficacy. By incorporating a patient's genetic profile into therapeutic decision-making, pharmacists can identify optimal drug choices and dosages while minimizing the risk of adverse events (AEs). This is particularly vital in polypharmacy scenarios, where the risk of drug-drug interactions and cumulative toxicity is high. Beyond improving medication safety, pharmacogenetics enhances clinical efficiency by reducing the reliance on trial-and-error prescribing. Personalized drug selection can lead to faster symptom control, fewer hospitalizations, and improved adherence—all of which contribute to better outcomes and a more streamlined care process.

It took more than 3 decades of evidence and advocacy to bring DPYD genotyping into US national guidelines since the connection between DPD deficiency and 5-FU toxicity was first reported in 1991. Although the European Medicines Agency mandated pretreatment DPD testing in Europe as early as 2020, and the UK’s National Health Service followed suit the same year, the US only reached a consensus in 2025.^2,3 In March this year, the National Comprehensive Cancer Network updated its guidelines—formally revised in June—to recommend that oncologists discuss DPYD testing with patients before starting fluoropyrimidine therapy. This change mirrored a January 2025 FDA safety alert and label update that urged providers to consider genetic testing, inform patients of the risks, and discuss available options.⁴ Although the US still stops short of requiring testing outright, this marks a critical turning point—shifting responsibility onto clinicians and paving the way for broader insurance coverage and adoption.

Real-World Evidence, Emerging Therapies, and Demonstrating Value

Technological advances are accelerating this progress. Artificial intelligence (AI) platforms such as PGxAI are now automating literature review, guideline development, and reimbursement documentation, enabling pharmacogenetic innovation to move from discovery to clinical application in months rather than decades.

The convergence of pharmacogenetic data with real-world evidence (RWE) has the potential to further refine medication safety and efficacy profiles. Pharmacists are instrumental in leveraging these data sets to identify actionable insights, particularly for complex patients who may deviate from trial populations. Emerging therapies—particularly targeted oncology treatments, medications for mental health conditions (including those under heightened controls such as psychedelics), cardiac care, and therapies for metabolic diseases, such as obesity and diabetes—often require genetically-informed dosing strategies. Pharmacists’ involvement in these areas is crucial, from patient education and dose adjustment to monitoring outcomes.

Moreover, integrating RWE with pharmacogenetic findings strengthens submissions to regulatory agencies and supports accelerated market access, bringing innovative treatments to patients more efficiently. Pharmacists also play a pivotal role in demonstrating the clinical and economic value of pharmacogenetically-guided therapies. By documenting reductions in AEs, treatment failures, and overall health care utilization, pharmacists can build the case for reimbursement of genetic testing and personalized regimens. In oncology, cardiology, psychiatry, and metabolic diseases—therapeutic areas with high variability in treatment response—genetic insights enable more targeted interventions. Demonstrating improved outcomes and cost-effectiveness helps ensure payer support and broadens access to precision therapies.

The Intersection of AI and Pharmacogenetics

Integrating AI technologies with pharmacogenetics presents powerful opportunities for enhancing medication therapy management. AI tools can combine genetic, clinical, and pharmacologic data to generate patient-specific recommendations in real time. As medication experts, pharmacists are ideally positioned to interpret these AI-generated insights, validate recommendations, and incorporate them into care plans. This approach not only improves the precision of pharmacotherapy but also mitigates the risk of harmful interactions, particularly in high-risk patients with multiple comorbidities.

AI-driven pharmacogenetics offers a scalable model for personalized care by streamlining decision-making, reducing medication-related harm, and optimizing clinical outcomes across diverse health care settings. Importantly, AI enables not only the fast-tracking of guideline development and clinical recommendations, but also active participation in clinical trials—seamlessly feeding data back into drug development pipelines to support the creation of more efficacious and safer therapies.⁵

In the biopharmaceutical industry, pharmacogenetics is increasingly employed to stratify patient populations and identify responders during drug development. Early identification of genetic markers associated with treatment efficacy or adverse reactions helps reduce late-stage clinical trial failures and improves the overall efficiency of the development pipeline. By facilitating the selection of genetically appropriate trial participants, pharmacogenetics enables more precise assessment of a therapy’s risk-benefit profile.

For pharmacy professionals, this evolution underscores the need for expertise in interpreting genetic data and integrating it into clinical workflows—particularly for newly approved or investigational agents.

AI-Powered Pharmacogenetics

Health systems integrating AI-powered pharmacogenetics into routine care can achieve improved clinical outcomes and stronger financial performance. Personalized prescribing is associated with fewer hospital admissions, shorter lengths of stay, and lower rates of medication errors, all of which reduce costs and improve quality metrics.

Pharmacists are central to these efforts, ensuring that pharmacogenetic data are interpreted correctly and applied consistently across inpatient and outpatient settings. Their role extends to formulary management, provider education, and protocol development—contributing to greater operational efficiency and patient satisfaction.

As genetic testing becomes more accessible, patients are increasingly empowered to take an active role in treatment decisions. Pharmacists are key educators, helping patients understand how their genetic profiles influence drug metabolism, efficacy, and safety.

This patient-centered approach builds trust, improves adherence, and fosters shared decision-making between patients and providers. By promoting genomic literacy and advocating for the integration of pharmacogenetics into everyday care, pharmacists help create a more participatory and personalized health care model.

Looking Ahead: Pharmacy at the Forefront of Precision Medicine

The intersection of pharmacogenetics and AI redefines the pharmacist’s role in precision medicine. Pharmacy professionals are uniquely positioned to lead this transformation—interpreting complex genetic data, optimizing therapeutic regimens, and ensuring safe, effective, individualized patient care.

As health care evolves toward a more personalized model, pharmacists will remain indispensable in translating genetic insights into actionable clinical decisions. By embracing AI-enhanced pharmacogenetics tools, they can not only elevate the standard of care but also streamline workflows, reduce costs, and improve outcomes across the health care continuum.

REFERENCES

1. Harris BE, Carpenter JT, Diasio RB. Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency. A potentially more common pharmacogenetic syndrome. Cancer. 1991;68(3):499-501. doi:10.1002/1097-0142(19910801)68:3<499::aid-cncr2820680309>3.0.co;2-f

2. Fluorouracil, capecitabine, tegafur and flucytosine: DPD testing to identify patients at increased risk of severe side effects. European Medicines Agency. Accessed July 21, 2025. https://www.ema.europa.eu/en/news/ema-recommendations-dpd-testing-prior-treatment-fluorouracil-capecitabine-tegafur-and-flucytosine

3. NHS England. NHS gives cancer patients genetic test to select best treatment. NHS Press Release. 2020. Accessed July 21, 2025. https://www.england.nhs.uk/2020/12/nhs-cancer-patients-genetic-test

4. FDA highlights importance of DPD deficiency discussions with patients prior to capecitabine or 5-FU treatment. FDA. 2025. Accessed July 21, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/safety-announcement-fda-highlights-importance-dpd-deficiency-discussions-patients-prior-capecitabine

5. Roses AD. Pharmacogenetics and drug development: the path to safer and more effective drugs. Nat Rev Genet. 2004;5(9):645-656. doi:10.1038/nrg1432