Pharmacogenomics-Guided Drug Safety: A Review Of Genetic Susceptibility To Adverse Drug Reactions And Personalized Pharmacovigilance

Abstract

Pharmacogenomics is an emerging component of precision medicine that investigates how genetic variation influences drug response, treatment efficacy, and susceptibility to adverse drug reactions (ADRs). Interindividual differences in drug-metabolizing enzymes, transporters, drug targets, and immune-related genes can alter pharmacokinetics and pharmacodynamics, contributing to treatment failure, toxicity, and preventable medication-related harm. Pharmacogenomics-guided drug safety offers an opportunity to identify genetically susceptible patients before prescribing and to integrate genetic information into personalized pharmacovigilance. This review examines the major genetic determinants of ADRs, clinically relevant gene–drug associations, and the application of pharmacogenomic testing in routine clinical practice. Important examples include CYP2C19-related clopidogrel response, CYP2D6-associated variability in opioid metabolism, TPMT and NUDT15 variants associated with thiopurine toxicity, HLA-B*57:01-associated abacavir hypersensitivity, and HLA-B*15:02-associated carbamazepine-induced Stevens–Johnson syndrome and toxic epidermal necrolysis. Evidence-based prescribing guidelines and regulatory recommendations support the clinical utility of selected pharmacogenomic biomarkers, although implementation varies across healthcare systems. Integrating pharmacogenomic data with electronic health records, clinical decision-support systems, medication surveillance, and post-marketing safety databases may improve early identification of high-risk patients and strengthen adverse-event prevention. Nevertheless, challenges remain, including genetic diversity, unequal access to testing, interpretation of uncertain variants, data privacy, cost-effectiveness, and limited representation of some populations in genomic research. Pharmacogenomics should therefore complement, rather than replace, clinical assessment, therapeutic drug monitoring, and conventional pharmacovigilance. A coordinated, ethically responsible framework combining pre-emptive testing, evidence-based prescribing, and longitudinal safety monitoring could improve medication outcomes and support more individualized, equitable, and proactive drug-safety practices.