Drug–gene and drug–drug interactions associated with tramadol and codeine therapy in the INGENIOUS trial
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.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
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