Context Adverse drug reactions are a significant cause of morbidity and mortality.
Although many adverse drug reactions are considered nonpreventable, recent
developments suggest these reactions may be avoided through individualization
of drug therapies based on genetic information, an application known as pharmacogenomics.
Objective To evaluate the potential role of pharmacogenomics in reducing the incidence
of adverse drug reactions.
Data Sources MEDLINE English-language only searches for adverse drug reaction 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 opinion.
Study Selection Detailed inclusion criteria were used to select studies. We included
18 of 333 adverse drug reaction studies and 22 of 61 variant allele review
Data Extraction All the investigators reviewed and coded articles using standardized
Data Synthesis We identified 27 drugs frequently cited in adverse drug reaction studies.
Among these drugs, 59% are metabolized by at least 1 enzyme with 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
(range, P = .006-P<.001).
Conclusions Our results suggest that drug therapy based on individuals' genetic
makeups may result in a clinically important reduction in adverse outcomes.
Our findings serve as a foundation for further research on how pharmacogenomics
can reduce the incidence of adverse reactions and on the resulting clinical,
societal, and economic implications.