Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy.


Crews KR(1), Monte AA(2), Huddart R(3), Caudle KE(1), Kharasch ED(4), Gaedigk A(5)(6), Dunnenberger HM(7), Leeder JS(5)(6), Callaghan JT(8), Samer CF(9), Klein TE(3), Haidar CE(1), Van Driest SL(10), Ruano G(11), Sangkuhl K(3), Cavallari LH(12), Müller DJ(13), Prows CA(14), Nagy M(15), Somogyi AA(16), Skaar TC(8).
Author information:
(1)Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
(2)Department of Emergency Medicine & Colorado Center for Personalized Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
(3)Department of Biomedical Data Science, Stanford University, Stanford, California, USA.
(4)Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA.
(5)Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children's Mercy Kansas City, Kanas City, Missouri, USA.
(6)School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, USA.
(7)Neaman Center for Personalized Medicine, NorthShore University HealthSystem, Evanston, Illinois, USA.
(8)Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
(9)Clinical Pharmacology and Toxicology Department, Geneva University Hospitals, Geneva, Switzerland.
(10)Departments of Pediatrics and Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
(11)Institute of Living Hartford Hospital, Genomas Lab of Personalized Health, University of Connecticut School of Medicine and University of Puerto Rico Medical Sciences, Hartford, Connecticut, USA.
(12)Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, University of Florida, Gainesville, Florida, USA.
(13)Department of Psychiatry, Campbell Family Mental Health Research Institute of CAMH, University of Toronto, Toronto, Ontario, Canada.
(14)Divisions of Human Genetics and Patient Services, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
(15)Department of Pharmaceutical Services, Children's Cancer Hospital Egypt 57357, Cairo, Egypt.
(16)Discipline of Pharmacology, Adelaide Medical School, University of Adelaide, Adelaide, Australia.


Opioids are mainly used to treat both acute and chronic pain. Several opioids are metabolized to some extent by CYP2D6 (codeine, tramadol, hydrocodone, oxycodone, and methadone). Polymorphisms in CYP2D6 have been studied for an association with the clinical effect and safety of these drugs. Other genes that have been studied for their association with opioid clinical effect or adverse events include OPRM1 (mu receptor) and COMT (catechol-O-methyltransferase). This guideline updates and expands the 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and codeine therapy and includes a summation of the evidence describing the impact of CYP2D6, OPRM1, and COMT on opioid analgesia and adverse events. We provide therapeutic recommendations for the use of CYP2D6 genotype results for prescribing codeine and tramadol and describe the limited and/or weak data for CYP2D6 and hydrocodone, oxycodone, and methadone, and for OPRM1 and COMT for clinical use.