{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:08:19Z","timestamp":1791821299902,"version":"4.3.4"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T00:00:00Z","timestamp":1679616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> The United States (US) ranks high, nationally, in opioid consumption. The ongoing increase in the misuse and mortality amid the opioid epidemic has been contributing to its rising cost. The worsening health and economic impact of opioid use disorder in the US warrants further attention. We, therefore, assessed commonly prescribed opioids to determine the opioids that were over-represented versus under-represented for adverse drug events (ADEs) to better understand their distribution patterns using the Food and Drug Administration\u2019s Adverse Event Reporting System (FAERS) while correcting for distribution using the Drug Enforcement Administration\u2019s Automation of Reports and Consolidated Orders System (ARCOS). Comparing the ratio of the percentage of adverse drug events as reported by the FAERS relative to the percentage of distribution as reported by the ARCOS database is a novel approach to evaluate post-marketing safety surveillance and may inform healthcare policies and providers to better regulate the use of these opioids.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We analyzed the adverse events for 11 prescription opioids, when correcting for distribution, and their ratios for three periods, 2006\u20132010, 2011\u20132016, and 2017\u20132021, in the US. The opioids include buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, and tapentadol. Oral morphine milligram equivalents (MMEs) were calculated by conversions relative to morphine. The relative ADEs of the selected opioids, opioid distributions, and ADEs relative to distribution ratios were analyzed for the 11 opioids.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Oxycodone, fentanyl, and morphine accounted for over half of the total number of ADEs (<jats:italic>n<\/jats:italic> = 667,969), while meperidine accounted for less than 1%. Opioid distributions were relatively constant over time, with methadone repeatedly accounting for the largest proportions. Many ADE-to-opioid distribution ratios increased over time, with meperidine (60.6), oxymorphone (11.1), tapentadol (10.3), and hydromorphone (7.9) being the most over-represented for ADEs in the most recent period. Methadone was under-represented (&amp;lt;0.20) in all the three periods.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The use of the FAERS with the ARCOS provides insights into dynamic changes in ADEs of the selected opioids in the US. There is further need to monitor and address the ADEs of these drugs.<\/jats:p>","DOI":"10.3389\/fphar.2023.1163976","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T04:29:40Z","timestamp":1679632180000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Variation in adverse drug events of opioids in the United States"],"prefix":"10.3389","volume":"14","author":[{"given":"Edward Y.","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth L.","family":"McCall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Piper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/ADM.0000000000000633","article-title":"The ASAM national practice guideline for the treatment of opioid use disorder: 2020 focused update","volume":"14","year":"2020","journal-title":"J. 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