PII-043 - ASSOCIATION BETWEEN CYP2D6 GENOTYPE-INHIBITOR INTERACTIONS AND PAIN-RELATED EMERGENCY DEPARTMENT VISITS IN CYP2D6-OPIOID-TREATED PATIENTS

N. Nahid¹, C. McDonough², Y. Wei³, Y. Gong⁴, P. Empey⁵, A. Haddad⁵, R. Fillingim⁶, J. Johnson³; ¹Ohio State University, Gainesville, FL, United States, ²Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida., Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida - Gainesville, Florida., USA, ³The Ohio State University, Columbus, OH, USA, ⁴University of Florida, GNV, United States, ⁵University of Pittsburgh, Pittsburgh, PA, USA, ⁶University of Florida, Gainesville, FL, USA.

Background: Hydrocodone (HC), tramadol (Tram), codeine (Cod), and oxycodone (Oxy) depend on activation by the highly polymorphic CYP2D6 to active metabolites. Variant CYP2D6 alleles may lead to null (poor metabolizers, PM), reduced (intermediate metabolizers, IM), normal (normal metabolizers, NM), or enhanced (ultra rapid metabolizers, UM) activities. CYP2D6 inhibitors can also markedly reduce CYP2D6 activity, leading to phenotypic PM or IM. We sought to determine the role of CYP2D6 genotype and drug interactions on CYP2D6 opioid efficacy, using emergency department (ED) visits as an indicator of poor pain control.

Methods: To test the association of CYP2D6 inhibitors and genetics together on pain control by HC/Tram/Cod/Oxy, we utilized electronic health records and CYP2D6 genetic data from the All of Us (AoU) Research Program. The association between ED visits and CYP2D6 phenotype considering genetics and inhibitors was tested using multivariable logistic regression. Subgroup analyses were also performed.

Results: We identified 33,116 patients (67% female; mean [SD] age, 51 [15.1]) with active prescriptions for Cod/HC/Tram/Oxy. Of these, 24,206 were classified as phenotypic pNM/pUM, while 8,910 were classified as phenotypic pIM/pPM, considering both genetics and CYP2D6 inhibitors. Patients with pPM/pIM status had a significantly higher crude rate of pain-related ED visits than those pNM/pUM status (2.42% vs. 1.8%), with an adjusted odds ratio (aOR) 1.23 and 95% CI 1.04 to 1.46. Similar findings were observed for HC/Tram/Cod-treated patients pIM/pPM versus pNM/pUM, (aOR 1.38; 95% CI: 1.10 to 1.75). Oxy-treated patients with pPM/pIM also had a higher crude rate of pain-related ED visits compared to pNM/pUM, though the difference was not statistically significant (aOR: 1.05, 95% CI: 0.81 to 1.35).

Conclusion: These data underscore the role of CYP2D6 genotype and drug interactions in pain management with opioids. The nonsignificant findings with oxycodone alone may be due to parent drug analgesic activity and reduced reliance on CYP2D6 metabolism versus the other drugs. Consideration of CYP2D6 genotype and drug interactions when prescribing HC/Tram/Cod/Oxy may have the potential to improve pain control.