Clinical Decision Support to Implement CYP2D6 Drug-Gene Interaction

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Opioid prodrugs like Codeine and tramadol are metabolized in the liver by the cytochrome P450 2D6 enzyme (CYP2D6) and transferred in to active metabolites responsible for the therapeutic effects which varies among individuals. High activity of CYP2D6 produces high levels of morphine and increases the risk of adverse effects and low activity produces low levels of morphine resulting in less pain control. [1]


Clinical Decision Support was implemented in to an EHR and rules were set to alert providers based on the results of pharmacogenomic(PGx) testing for CYP2D6 and the documentation of the genotypes and phenotypes in the EHR. The CDS rules displayed alerts only for high or low activity. All the alerts had a clear message indicating the clinical impact of the specific drug-gene interaction.


A total of 206 events were triggered by the CPOE screen rule and 45 (21.8%) of them were unreadable. The main cause of unreadable result was lack of discrete values on the Pharmacogenomic reports. The other 161 events displayed alerts due to increased activity (121, 75%) or decreased activity (40, 25%)


Implementation of CDS integrated in the EHR to selectively prevent CYP2D6 related drug-gene interactions is feasible and has shown positive outcomes.The level of CYP2D6 metabolic activity can be predicted by pharmacogenomic testing, and concomitant use of clinical decision support has the potential to prevent adverse effects from those drugs metabolized by this enzyme.


Its great that studies are being conducted to prevent drug-gene interactions, which leads to adverse drug reactions in patients, especially by the effective use of Clinical Decision Support. To overcome such effects, online database like Drug-Gene Interaction Database can be used to search for the disease genes that have the potential to be drugged. Two limitations of the study are: 1) the need for additional standard for pharmocogenomic lab report to enable stable data integration with EHR to facilitate CDS interventions and 2) the need to find a way to prevent unnecessary and repetitive CDS alerts.

The practical implementation of PGx data into a CDS system would require a significant percentage of patients to have undergone PGx testing and made those results available to the system. At the present time it is unclear how feasible this level of coverage is from a cost perpective.


  1. CYP2D6 Drug-Gene Interaction2015Clinical Decision Support to Implement CYP2D6 Drug-Gene Interaction