{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:35:46Z","timestamp":1791873346847,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,6,11]],"date-time":"2018-06-11T00:00:00Z","timestamp":1528675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In recognition of potential for increased overdose risk, drug labels for extended\u2010release and long\u2010acting (ER\/LA) opioids emphasize the need for established opioid tolerance prior to initiating high dosages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Describe the proportion of patients with opioid tolerance prior to initiation of 90 morphine milligram equivalents (MME) ER\/LA opioids and examine subsequent risk of opioid poisoning.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used Truven Health Analytics' MarketScan Databases (2006\u20102015) to identify patients initiating ER\/LA opioids \u226590 MME. We examined prescription histories and describe the proportion of initiators with opioid tolerance (defined as \u22657\u00a0days of 60 MME in the prior 14\u00a0days). We adjusted for age, sex, year of initiation, and baseline comorbidities using inverse probability of treatment weighted Cox proportional hazards models. We estimated adjusted hazard ratios and 95% confidence intervals for the effect of opioid tolerance on the risk of clinically recognized opioid poisoning (based on diagnosis codes) in specific periods (0\u20107, 8\u201030, 31\u201090, and 91\u2010365\u00a0days) following initiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 372\u00a0038 initiators, 38% did not meet opioid tolerance criteria. The proportion of nontolerant initiators was highest among those initiating methadone (44%) and fentanyl (42%). Nontolerant patients were 37% more likely to be diagnosed with opioid poisoning (adjusted hazard ratios\u00a0=\u00a01.37 [1.07, 1.76]) in the week following ER\/LA initiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Over one\u2010third of patients initiating \u226590 MME ER\/LA opioids did not have evidence of opioid tolerance. The 7\u00a0days following high dose ER\/LA initiation may represent a high\u2010risk period for clinically diagnosed opioid poisoning in patients who do not have prior opioid tolerance.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.4572","type":"journal-article","created":{"date-parts":[[2018,6,11]],"date-time":"2018-06-11T07:10:11Z","timestamp":1528701011000},"page":"39-47","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Opioid tolerance and clinically recognized opioid poisoning among patients prescribed extended\u2010release long\u2010acting opioids"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2655-192X","authenticated-orcid":false,"given":"Jessica C.","family":"Young","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1108-0689","authenticated-orcid":false,"given":"Jennifer L.","family":"Lund","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4098-605X","authenticated-orcid":false,"given":"Nabarun","family":"Dasgupta","sequence":"additional","affiliation":[{"name":"Injury Prevention Research Center University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3756-7540","authenticated-orcid":false,"given":"Michele","family":"Jonsson Funk","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40266-017-0482-6"},{"issue":"3","key":"e_1_2_10_3_1","first-page":"21","article-title":"Classifying patient histories in Medicare claims: Fixed vs. all available lookbacks","volume":"25","author":"Conover MMST","year":"2016","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"e_1_2_10_4_1","unstructured":"RiosM.Fueled by Aging Baby Boomers Nation's Older Population to Nearly Double in the Next 20 Years Census Bureau Reports.2014[cited Release Number: CB14\u201384 January 11 2018]; 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