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Drug–gene and drug–drug interactions associated with tramadol and codeine therapy in the INGENIOUS trial

    Cathy R Fulton

    Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA

    Department of Health Informatics, Indiana University School of Informatics and Computing, Indianapolis, IN 46202, USA

    ,
    Yong Zang

    Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN 46202, USA

    ,
    Zeruesenay Desta

    Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA

    ,
    Marc B Rosenman

    Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA

    Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA

    Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA

    ,
    Ann M Holmes

    Richard M Fairbanks School of Public Health, Indiana University-Purdue University Indianapolis, IN 46202, USA

    ,
    Brian S Decker

    Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA

    ,
    Yifei Zhang

    Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN 46202, USA

    ,
    John T Callaghan

    Regenstrief Institute for Health Care, Indianapolis, IN 46202, USA

    ,
    Victoria M Pratt

    Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA

    ,
    Kenneth D Levy

    Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA

    ,
    Brandon T Gufford

    Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA

    ,
    Paul R Dexter

    Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA

    Richard L Roudebush Veteran Affairs Medical Center, Indianapolis, IN 46202, USA

    ,
    Todd C Skaar

    Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA

    &
    Michael T Eadon

    *Author for correspondence: Tel.: +1 317 274 2502; Fax: +1 317 274 8575;

    E-mail Address: meadon@iupui.edu

    Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA

    Published Online:https://doi.org/10.2217/pgs-2018-0205

    Background: 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.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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