Drug–gene and drug–drug interactions associated with tramadol and codeine therapy in the INGENIOUS trial. (20th February 2019)

• Record Type: Journal Article
• Authors: Fulton, Cathy R; Zang, Yong; Desta, Zeruesenay; Rosenman, Marc B; Holmes, Ann M; Decker, Brian S; Zhang, Yifei; T Callaghan, John; Pratt, Victoria M; Levy, Kenneth D; Gufford, Brandon T; Dexter, Paul R; Skaar, Todd C; Eadon, Michael T
• Is Part Of: Pharmacogenomics. Volume 20:Number 6(2019)
• Page Start: 397
• Page End: 408
• Publication Date: 2019-02-20
• Subjects: adverse side effects -- CYP2D6 -- IGNITE -- INGENIOUS -- pharmacogenetics; opioids -- pharmacogenomics -- phenoconversion; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs-2018-0205
• Languages: English
• ISSNs: 1462-2416

Abstract

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.