{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:11:36Z","timestamp":1762866696407},"reference-count":19,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,8,22]],"date-time":"2015-08-22T00:00:00Z","timestamp":1440201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Endo Pharmaceuticals"},{"name":"Mallinckrodt"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pain Practice"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To characterize the safety of immediate\u2010release (IR)\/extended\u2010release (ER) oxycodone (OC)\/acetaminophen (APAP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data were assessed from 9 phase 1 trials in healthy volunteers and recreational users of prescription opioids (<jats:italic>N<\/jats:italic>\u00a0=\u00a0405), including 5 single\u2010dose and 3 multidose open\u2010label pharmacokinetic studies of IR\/ER OC\/APAP and\u00a0active comparators; and 1 randomized, controlled, single\u2010dose human abuse potential (HAP) study comparing IR\/ER OC\/APAP, IR OC\/APAP, and placebo in recreational users of opioids; and 2 phase 3 trials (<jats:italic>N<\/jats:italic>\u00a0=\u00a0701) including a 48\u2010hour placebo\u2010controlled safety and efficacy study in patients with moderate to severe postbunionectomy pain with a 14\u2010day open\u2010label safety extension and a long\u2010term (\u2264\u00a035\u00a0days) open\u2010label safety study in patients with chronic osteoarthritis pain or chronic low back pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Adverse events (AEs) experienced by \u2265\u00a010% of participants receiving IR\/ER OC\/APAP in all trials were pruritus, nausea, vomiting, dizziness, headache, and somnolence; these AEs occurred with similar frequency for equianalgesic doses of IR OC\/APAP and IR OC but less frequently for IR tramadol HCl\/APAP. In the HAP study, crushing IR\/ER or IR OC\/APAP tablets did not increase frequency of AEs. Constipation was experienced by &lt;\u00a010% of participants receiving IR\/ER OC\/APAP. No serious (SAE) or severe AEs were reported in phase 1 trials. In phase 3 trials of 8 reported SAEs, only 1 treatment\u2010related SAE (hypersensitivity to placebo) required treatment discontinuation. No clinically meaningful changes in vital signs, oxygen saturation, electrocardiograms, or laboratory values were reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Safety and tolerability of IR\/ER OC\/APAP are similar to other low\u2010dose opioid\/APAP analgesics.<\/jats:p><\/jats:sec>","DOI":"10.1111\/papr.12324","type":"journal-article","created":{"date-parts":[[2015,8,22]],"date-time":"2015-08-22T08:03:21Z","timestamp":1440230601000},"page":"856-868","source":"Crossref","is-referenced-by-count":4,"title":["Safety and Tolerability of Biphasic Immediate\u2010Release\/Extended\u2010Release Oxycodone\/Acetaminophen Tablets: Analysis of 11 Clinical Trials"],"prefix":"10.1111","volume":"16","author":[{"given":"Thomas","family":"Barrett","sequence":"first","affiliation":[{"name":"Clinical Research Mallinckrodt Pharmaceuticals Hazelwood Missouri U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Kostenbader","sequence":"additional","affiliation":[{"name":"Mallinckrodt Pharmaceuticals Hazelwood Missouri U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srinivas","family":"Nalamachu","sequence":"additional","affiliation":[{"name":"International Clinical Research Institute Overland Park Kansas U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Giuliani","sequence":"additional","affiliation":[{"name":"Research and Development Mallinckrodt Pharmaceuticals Hazelwood Missouri U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jim L.","family":"Young","sequence":"additional","affiliation":[{"name":"Clinical Affairs &amp; Program Management Research and Development Mallinckrodt Pharmaceuticals Hazelwood Missouri U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,8,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00045391-200105000-00006"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2008.10.008"},{"key":"e_1_2_7_4_1","volume-title":"Oxycodone Hydrochloride and Acetaminophen Extended\u2010release Tablets","author":"Xartemis\u2122 XR","year":"2014"},{"key":"e_1_2_7_5_1","unstructured":"US Food and Drug Administration.FDA Drug Safety Communication: Prescription Acetaminophen Products to be Limited to 325\u00a0mg per Dosage Unit; Boxed Warning will Highlight Potential for Severe Liver Failure. 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