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

Cathy R. Fulton, Yong Zang, Zeruesenay Desta, Marc Rosenman, Ann Holmes, Brian Decker, Yifei Zhang, John T Callaghan, Victoria M. Pratt, Kenneth Levy, Brandon T. Gufford, Paul Dexter, Todd Skaar, Michael Eadon

Research output: Contribution to journalArticle

1 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



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

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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