Pharmacogenomics of Adverse Drug Reactions: Integrating Genetic Biomarkers into Precision Pharmacotherapy

Abstract

Adverse drug reactions (ADRs) remain a major global healthcare challenge, accounting for significant morbidity, mortality, treatment failure, and increased healthcare expenditure. Although clinical factors such as age, comorbidities, organ function, and polypharmacy contribute to ADR susceptibility, they inadequately explain the marked interindividual variability in drug response. Pharmacogenomics has emerged as a transformative approach to precision medicine by identifying inherited genetic variants that influence drug metabolism, transport, efficacy, and toxicity. This review critically examines the role of pharmacogenomic testing in predicting, preventing, and managing ADRs, with emphasis on clinically actionable pharmacogenes including CYP2D6, CYP2C19, TPMT, NUDT15, HLA-B15:02, HLA-B57:01, and HLA-B 58:01. Evidence from international pharmacogenomic guidelines demonstrates that genotype-guided prescribing significantly reduces severe hypersensitivity reactions, drug toxicity, and treatment failure while improving therapeutic efficacy and patient safety. The review further discusses current clinical applications, implementation challenges, ethical considerations, and emerging advances in genomic technologies, artificial intelligence, and clinical decision-support systems. The integration of pharmacogenomics into routine healthcare has the potential to optimize individualized drug therapy, minimize preventable ADRs, and accelerate the transition toward precision medicine, ultimately improving clinical outcomes and healthcare quality.