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However, the reasoning behind these warnings is often unclear and frequently lacks clinical validation. Reported reactions may include skin rashes, itching, severe vomiting, fainting or respiratory arrest occurring during postoperative recovery where opioids were administered. In many cases, there is also uncertainty about which specific opioid was used. An allergy warning to one opioid further raises the question of whether the patient can tolerate other opioids. In this review, we address the exceedingly rare IgE\u2010mediated opioid allergy and cross\u2010reactivity between opioids, along with non\u2013immune\u2010mediated histamine release and other adverse effects of opioids that patients or clinicians may mistake for allergic reactions. We propose a simple risk stratification algorithm for the clinical management of patients labelled as opioid allergic\u2014helping to distinguish who should be referred for allergy evaluation and who can safely be treated with opioids with or without antihistamine pre\u2010treatment.<\/jats:p>","DOI":"10.1111\/bcpt.70182","type":"journal-article","created":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T11:35:29Z","timestamp":1766662529000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hypersensitivity to Opioids: Prevalence, Mechanisms, Diagnosis and Management"],"prefix":"10.1111","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3612-5828","authenticated-orcid":false,"given":"Kenneth","family":"Skov","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Zealand University Hospital  Koege Denmark"},{"name":"Department of Clinical Medicine Copenhagen University  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva\u00a0Aggerholm","family":"S\u00e6dder","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gitte\u00a0Krogh","family":"Madsen","sequence":"additional","affiliation":[{"name":"General Practice Roskilde Laegehus  Roskilde Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter\u00a0Gaarsdal","family":"Uhrbrand","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas\u00a0Halgreen","family":"Eiset","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7777-4501","authenticated-orcid":false,"given":"Lene\u00a0Heise","family":"Garvey","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Copenhagen University  Copenhagen Denmark"},{"name":"Allergy Clinic, Department of Dermatology and Allergy Copenhagen University Hospital\u2010Herlev and Gentofte  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jamia\/ocv143"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0310057X1204000204"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-022-03402-2"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(93)90581-M"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/15360288.2024.2448531"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028019860521"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.all.0000011034.96839.aa"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-021-03068-2"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ai.2017.06.002"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12617"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejp.2180"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.67523"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000002184"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-199819030-00002"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199207000-00023"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2019.08.010"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-023-03596-z"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-800634-4.00043-3"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14105"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/1178646919873925"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcg109"},{"issue":"41","key":"e_1_2_8_23_1","article-title":"Unwarranted Allergy Labels Against Opioids","volume":"186","author":"Uhrbrand P. 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