Pharmacogenomics in Emergency Care: Actionable Genetic Variability, Drug-Related Toxicity, and Precision Prescribing

Abstract

Pharmacogenomic variability represents an increasingly relevant determinant of therapeutic response, drug toxicity, and treatment failure in emergency and internal medicine. This study analyzed the clinical applicability of actionable gene–drug interactions associated with acute pharmacological decision-making, severe adverse drug reactions, and the potential integration of genomic information into emergency-care workflows. A structured integrative review based on the Scientific Method was conducted using pharmacogenomic guidelines, implementation studies, regulatory resources, and clinically oriented evidence. Particular attention was given to associations involving CYP2D6, CYP2C19, CYP2C9, VKORC1, G6PD, RYR1, CACNA1S, HLA-B, SLCO1B1, TPMT, and NUDT15. The evidence demonstrated that pharmacogenomic-guided prescribing can be associated with measurable differences in medication safety. In the PREPARE study, clinically relevant adverse drug reactions occurred in 21.0% of patients managed with genotype-guided treatment compared with 27.7% receiving standard care. In an emergency department cohort, actionable pharmacogenomic variants were identified in 99% of patients, while clinically relevant gene–drug pairs were detected in 53%. The analyzed interactions were mainly associated with altered drug metabolism, modified pharmacological sensitivity, severe genetically mediated adverse reactions, and delayed toxicities capable of producing acute-care presentations. Pharmacogenomic information showed potential utility for medication selection, dose modification, drug avoidance, risk stratification, and prevention of recurrent adverse events. Nevertheless, its clinical value depends on integration with renal and hepatic function, comorbidities, drug interactions, disease severity, and conventional emergency assessment. Preemptive testing integrated into electronic health records appears to be one of the most feasible models for emergency implementation because it allows actionable results to be available before time-sensitive treatment decisions. Pharmacogenomics may therefore contribute to a more preventive, individualized, and precise approach to medication safety in acute care, although prospective emergency-specific studies, interoperable systems, population-diverse validation, and equitable access remain necessary for broader implementation.