Pharmacogenomics in Primary Care: A Narrative Review of DNA-Guided Prescribing in Multimorbidity and Polypharmacy

Pharmacogenomics can convert stable DNA variation into prescribing information, but its value in primary care depends on whether a result changes a decision at the right moment. This narrative review critically examines selected actionable gene–drug pairs, implementation models, conflicting evidence, and unresolved questions for family physicians managing multimorbidity and polypharmacy. A targeted search of PubMed/MEDLINE and current pharmacogenomic guideline resources was updated through 14 August 2026, prioritizing clinical guidelines, randomized and pragmatic trials, implementation studies, and primary-care evidence. Guideline actionability describes how an available result can guide treatment; it does not by itself establish that testing should be ordered. Selected examples include clopidogrel, statins, metoprolol, antidepressants, codeine and tramadol, proton-pump inhibitors, nonsteroidal anti-inflammatory drugs, and warfarin, together with shared-care medicines such as thiopurines and carbamazepine. In PREPARE, a defined 12-gene panel linked to prescribing recommendations reduced clinically relevant adverse drug reactions within a specific European workflow. Other trials showed that benefit is drug-, population-, comparator-, and workflow-dependent. Pharmacogenomics does not replace assessment of organ function, interactions, adherence, frailty, or patient preference. This review proposes selective, clinically triggered panel testing as a pragmatic model for primary care, with structured, reusable results and concise decision support. Future work should define who benefits, improve ancestry representation, account for phenoconversion, and demonstrate health-system-specific cost-effectiveness. Pharmacogenomics is best understood as an additional medication-safety input rather than a stand-alone precision-medicine solution.