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

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, Michael T. Eadon

Research output: Contribution to journalArticle

2 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)397-408
Number of pages12
Issue number6
StatePublished - Apr 1 2019


  • CYP2D6
  • adverse side effects
  • pharmacogenetics; opioids
  • pharmacogenomics
  • phenoconversion

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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