Potential role of pharmacogenomics in reducing adverse drug reactions - A systematic review

Context Adverse drug reactions are a significant cause of morbidity and mor tality. Although many adverse drug reactions are considered nonpreventable, recent developments suggest these reactions may be avoided through individ ualization of drug therapies based on genetic information, an application k nown as pharmacogenomics. Objective To evaluate the potential role of pharmacogenomics in reducing th e incidence of adverse drug reactions. Data Sources MEDLINE English-language only searches for adverse drug reacti on studies published between January 1995 and June 2000 and review articles of variant alleles of drug-metabolizing enzymes published between January 1997 and August 2000. We also used online resources, texts, and expert opin ion. Study Selection Detailed inclusion criteria were used to select studies. We included 18 of 333 adverse drug reaction studies and 22 of 61 variant alle le review articles. Data Extraction All the investigators reviewed and coded articles using sta ndardized abstracting forms. Data Synthesis We identified 27 drugs frequently cited in adverse drug reac tion studies. Among these drugs, 59% are metabolized by at least 1 enzyme w ith a variant allele known to cause poor metabolism. Conversely, only 7% to 22% of randomly selected drugs are known to be metabolized by enzymes with this genetic variability (range, P=.006-P<.001). Conclusions Our results suggest that drug therapy based on individuals' gen etic makeups may result in a clinically important reduction in adverse outc omes. Our findings serve as a foundation for further research on how pharma cogenomics can reduce the incidence of adverse reactions and on the resulti ng clinical, societal, and economic implications.