{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:43:00Z","timestamp":1792701780174,"version":"4.5.0"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1011251"],"award-info":[{"award-number":["1011251"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    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\n                    <jats:italic>OPRM1<\/jats:italic>\n                    (mu receptor) and\n                    <jats:italic>COMT<\/jats:italic>\n                    (catechol\u2010O\u2010methyltransferase). This guideline updates and expands the 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    genotype and codeine therapy and includes a summation of the evidence describing the impact of\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    ,\n                    <jats:italic>OPRM1<\/jats:italic>\n                    , and\n                    <jats:italic>COMT<\/jats:italic>\n                    on opioid analgesia and adverse events. We provide therapeutic recommendations for the use of\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    genotype results for prescribing codeine and tramadol and describe the limited and\/or weak data for\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    and hydrocodone, oxycodone, and methadone, and for\n                    <jats:italic>OPRM1<\/jats:italic>\n                    and\n                    <jats:italic>COMT<\/jats:italic>\n                    for clinical use.\n                  <\/jats:p>","DOI":"10.1002\/cpt.2149","type":"journal-article","created":{"date-parts":[[2021,1,2]],"date-time":"2021-01-02T10:33:03Z","timestamp":1609583583000},"page":"888-896","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":436,"title":["Clinical Pharmacogenetics Implementation Consortium Guideline for\n                    <i>CYP2D6<\/i>\n                    ,\n                    <i>OPRM1<\/i>\n                    , and\n                    <i>COMT<\/i>\n                    Genotypes and Select Opioid Therapy"],"prefix":"10.1111","volume":"110","author":[{"given":"Kristine R.","family":"Crews","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences St. Jude Children\u2019s Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew A.","family":"Monte","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine &amp; Colorado Center for Personalized Medicine University of Colorado School of Medicine Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Huddart","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science Stanford University Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly E.","family":"Caudle","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences St. Jude Children\u2019s Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan D.","family":"Kharasch","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Duke University School of Medicine Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Gaedigk","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Toxicology &amp; Therapeutic Innovation Children\u2019s Mercy Kansas City Kanas City Missouri USA"},{"name":"School of Medicine University of Missouri\u2010Kansas City Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry M.","family":"Dunnenberger","sequence":"additional","affiliation":[{"name":"Neaman Center for Personalized Medicine NorthShore University HealthSystem Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Steven","family":"Leeder","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Toxicology &amp; Therapeutic Innovation Children\u2019s Mercy Kansas City Kanas City Missouri USA"},{"name":"School of Medicine University of Missouri\u2010Kansas City Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Callaghan","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Clinical Pharmacology Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline Flora","family":"Samer","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Toxicology Department Geneva University Hospitals Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teri E.","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science Stanford University Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrine E.","family":"Haidar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences St. Jude Children\u2019s Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara L.","family":"Van Driest","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Medicine Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gualberto","family":"Ruano","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Sangkuhl","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science Stanford University Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa H.","family":"Cavallari","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Campbell Family Mental Health Research Institute of CAMH University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia A.","family":"Prows","sequence":"additional","affiliation":[{"name":"Divisions of Human Genetics and Patient Services Cincinnati Children\u2019s Hospital Medical Center Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Services Children\u2019s Cancer Hospital Egypt 57357 Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew A.","family":"Somogyi","sequence":"additional","affiliation":[{"name":"Discipline of Pharmacology Adelaide Medical School University of Adelaide Adelaide Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd C.","family":"Skaar","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Clinical Pharmacology Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,9]]},"reference":[{"key":"e_1_2_12_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.254"},{"key":"e_1_2_12_2_1","unstructured":"PharmGKB.Gene Reference Materials for CYP2D6<https:\/\/www.PharmGKBorg\/page\/cyp2d6RefMaterials>. 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