{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T09:27:52Z","timestamp":1786958872976,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"abstract":"<jats:p>\n                    Tramadol is frequently co\u2010prescribed with oxycodone or hydrocodone after surgery under the assumption that its dual mechanism of action provides an opioid\u2010sparing benefit. However, evidence supporting this practice is limited and inconsistent. We conducted a secondary analysis of the multicenter IGNITE ADOPT\u2010PGx pragmatic trial of patients undergoing elective surgery who were prescribed oxycodone alone (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009317) versus tramadol + oxycodone (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200996), or hydrocodone alone (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009563) versus tramadol + hydrocodone (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200942). Co\u2010primary outcomes of this study were cumulative morphine milligram equivalents (MME) consumed during the 10\u2009days following surgery and composite pain scores at day 10 defined as the sum of current pain and average and worst pain in the past 7\u2009days (score ranges from 3 to 15). Inverse probability of treatment weighting (IPTW) was used to adjust for demographic characteristics, comorbidities, and concomitant analgesics. Sensitivity analyses restricted to CYP2D6 normal metabolizers and sites prescribing both monotherapy and combination therapy and subgroup analysis including total knee arthroplasty patients were conducted. Compared to oxycodone alone, the combination of oxycodone and tramadol was associated with higher MME (adjusted mean 205.2 vs 122.5;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001) and lower mobility, without meaningful differences in pain scores (adjusted mean 9.6 vs 9.4;\n                    <jats:italic>P\u2009=\u20090.41<\/jats:italic>\n                    ). Similar findings were observed for hydrocodone\u2010only vs hydrocodone + tramadol groups. Results were consistent in sensitivity and subgroup analyses. Co\u2010administration of tramadol with oxycodone or hydrocodone was associated with substantially higher total MME and reduced mobility without any demonstrable improvement in pain control.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70434","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:56:47Z","timestamp":1786957007000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tramadol Co\u2010Administration with Oxycodone or Hydrocodone Increases Opioid Burden without Improving Postoperative Pain Control"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2190-7555","authenticated-orcid":false,"given":"Noor A.","family":"Nahid","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics College of Medicine, The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9539-8167","authenticated-orcid":false,"given":"Ahmed I.","family":"Soliman","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Science College of Pharmacy, The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4849-5415","authenticated-orcid":false,"given":"Jordan F.","family":"Baye","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice South Dakota State University  Brookings South Dakota USA"},{"name":"Sanford Health Imagenetics  Sioux Falls South Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5089-9286","authenticated-orcid":false,"given":"Natasha J.","family":"Petry","sequence":"additional","affiliation":[{"name":"Sanford Health Imagenetics  Sioux Falls South Dakota USA"},{"name":"Department of Pharmacy Practice School of Pharmacy, North Dakota State University  Fargo North Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8312-3695","authenticated-orcid":false,"given":"Chancellor F.","family":"Gray","sequence":"additional","affiliation":[{"name":"Florida Orthopaedic Institute  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0086-8339","authenticated-orcid":false,"given":"Rachel A.","family":"Myers","sequence":"additional","affiliation":[{"name":"Clinical Research Unit, Department of Medicine Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica N.","family":"Elwood","sequence":"additional","affiliation":[{"name":"Center of Pharmacogenomic and Precision Medicine University of Florida, College of Pharmacy  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth C.","family":"Harris","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine  Durham North Carolina 27701 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9078-845X","authenticated-orcid":false,"given":"Hrishikesh","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine  Durham North Carolina 27701 USA"},{"name":"Department of Biostatistics and Bioinformatics Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Volpi","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7765-2988","authenticated-orcid":false,"given":"Renee","family":"Rider","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Dexter","sequence":"additional","affiliation":[{"name":"Regenstrief Institute, Indiana University  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7553-0749","authenticated-orcid":false,"given":"Josh F.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3849-374X","authenticated-orcid":false,"given":"Todd C.","family":"Skaar","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5547-405X","authenticated-orcid":false,"given":"Hari K.","family":"Parvataneni","sequence":"additional","affiliation":[{"name":"Florida Orthopaedic Institute  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7184-5292","authenticated-orcid":false,"given":"Larisa H.","family":"Cavallari","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine College of Pharmacy, University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9847-1932","authenticated-orcid":false,"given":"Julie A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine College of Pharmacy, University of Florida  Gainesville Florida USA"},{"name":"Clinical and Translational Science Institute The Ohio State University  Columbus Ohio USA"},{"name":"Department of Internal Medicine College of Medicine, The Ohio State University  Columbus Ohio USA"},{"name":"Department of Pharmaceutics &amp; Pharmacology College of Pharmacy, The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the IGNITE Pragmatic Trial Network 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