• Cathy R Fulton, Yong Zang, Zeruesenay Desta, Marc B Rosenman, Ann M Holmes, Brian S Decker, Yifei Zhang, John T Callaghan, Victoria M Pratt, Kenneth D Levy, Brandon T Gufford, Paul R Dexter, Todd C Skaar, and Michael T Eadon.
• Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
• Pharmacogenomics. 2019 Apr 1; 20 (6): 397-408.

AbstractBackground: 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.

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