Aim: Drug–drug interactions (DDIs) are a widely recognized major cause of adverse drug reactions, but two other newly described important types of interactions also exist: drug–gene interactions (DGIs) and drug–drug–gene interactions (DDGIs). A drug–gene interaction occurs when a patient's genetic CYP450 type (e.g., CYP2D6 poor metabolizer) affects that patient's ability to clear a drug. A drug–drug–gene interaction occurs when the patient's CYP450 genotype and another drug in the patient's regimen (e.g., a CYP2D6 inhibitor) affect that individual's ability to clear a drug. Their prevalence has not been previously described. This pilot study investigates the frequency of DDIs, DGIs and DDGIs in a sample of CYP450 tested individuals.
Materials & Methods: The investigators conducted a retrospective analysis of 1143 individuals with known CYP2D6, CYP2C19 and CYP2C9 genotypes. Using the individuals' medication lists and YouScript®, a software tool to analyze cumulative DDIs and DGIs, the prevalence of DDI, DGI and DDGIs was analyzed.
Results: A total of 1053 potential major or substantial interactions were identified in 501 individuals. DDIs accounted for 66.1% of the total interactions. The remaining 33.9% of interactions were DGIs (14.7%) and DDGIs (19.2%). When compared with DDIs alone, DGIs and DDGIs increased the total number of potentially clinically significant interactions by 51.3%.
Conclusion: In the future, identifying DGIs and DDGIs may lead to a more comprehensive method of identifying individuals who are at risk for adverse drug reactions.
Pharmacogenomics. 2014;15(5):655-665. © 2014
Future Medicine Ltd.