Cathy R Fulton1,2, Yong Zang3, Zeruesenay Desta1, Marc B Rosenman1,4,5, Ann M Holmes6, Brian S Decker1, Yifei Zhang3, John T Callaghan7, Victoria M Pratt1, Kenneth D Levy1, Brandon T Gufford1, Paul R Dexter1,8, Todd C Skaar1, Michael T Eadon1. 1. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. 2. Department of Health Informatics, Indiana University School of Informatics and Computing, Indianapolis, IN 46202, USA. 3. Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN 46202, USA. 4. Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA. 5. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. 6. Richard M Fairbanks School of Public Health, Indiana University-Purdue University Indianapolis, IN 46202, USA. 7. Regenstrief Institute for Health Care, Indianapolis, IN 46202, USA. 8. Richard L Roudebush Veteran Affairs Medical Center, Indianapolis, IN 46202, USA.
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.
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.
Authors: M T Eadon; Z Desta; K D Levy; B S Decker; R C Pierson; V M Pratt; J T Callaghan; M B Rosenman; J S Carpenter; A M Holmes; C A McDonald; E A Benson; A S Patil; R Vuppalanchi; B T Gufford; N Dave; J D Robarge; M A Hyder; D M Haas; R P Kreutz; P R Dexter; T C Skaar; D A Flockhart Journal: Clin Pharmacol Ther Date: 2016-03-31 Impact factor: 6.875
Authors: Yvan Gasche; Youssef Daali; Marc Fathi; Alberto Chiappe; Silvia Cottini; Pierre Dayer; Jules Desmeules Journal: N Engl J Med Date: 2004-12-30 Impact factor: 91.245
Authors: Roseann S Gammal; Kristine R Crews; Cyrine E Haidar; James M Hoffman; Donald K Baker; Patricia J Barker; Jeremie H Estepp; Deqing Pei; Ulrich Broeckel; Winfred Wang; Mitchell J Weiss; Mary V Relling; Jane Hankins Journal: Pediatrics Date: 2016-07 Impact factor: 7.124