Fulton, Cathy R.Zang, YongDesta, ZeruesenayRosenman, Marc B.Holmes, Ann M.Decker, Brian S.Zhang, YifeiCallaghan, John T.Pratt, Victoria M.Levy, Kenneth D.Gufford, Brandon T.Dexter, Paul R.Skaar, Todd C.Eadon, Michael T.2020-06-242020-06-242019-04Fulton, C. R., Zang, Y., Desta, Z., Rosenman, M. B., Holmes, A. M., Decker, B. S., Zhang, Y., T Callaghan, J., Pratt, V. M., Levy, K. D., Gufford, B. T., Dexter, P. R., Skaar, T. C., & Eadon, M. T. (2019). Drug-gene and drug-drug interactions associated with tramadol and codeine therapy in the INGENIOUS trial. Pharmacogenomics, 20(6), 397–408. https://doi.org/10.2217/pgs-2018-0205https://hdl.handle.net/1805/23075Background: Tramadol and codeine are metabolized by CYP2D6 and are subject to drug-gene and drug-drug interactions. Methods: This interim analysis examined prescribing behavior and efficacy in 102 individuals prescribed tramadol or codeine while receiving pharmaco-genotyping as part of the INGENIOUS trial (NCT02297126). Results: Within 60 days of receiving tramadol or codeine, clinicians more frequently prescribed an alternative opioid in ultrarapid and poor metabolizers (odds ratio: 19.0; 95% CI: 2.8-160.4) as compared with normal or indeterminate metabolizers (p = 0.01). After adjusting the CYP2D6 activity score for drug-drug interactions, uncontrolled pain was reported more frequently in individuals with reduced CYP2D6 activity (odds ratio: 0.50; 95% CI: 0.25-0.94). Conclusion: Phenoconversion for drug-drug and drug-gene interactions is an important consideration in pharmacogenomic implementation; drug-drug interactions may obscure the potential benefits of genotyping.en-USPublisher PolicyAdverse side effectsCYP2D6IGNITEINGENIOUSPharmacogeneticsOpioidsPharmacogenomicsPhenoconversionArticle