{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T23:27:36Z","timestamp":1780442856722,"version":"3.54.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Itraconazole is the treatment of choice for many fungal infections, including histoplasmosis. While the tolerability of itraconazole has been described in short-term trial settings, there are few studies on side effects during long-term therapy. Fluconazole, which is usually thought to be less toxic, is associated with 52% toxicity in long-term treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To determine the frequency, types, and timing of side effects from itraconazole therapy, the resulting changes to treatment plans, and associations between patient characteristics and itraconazole serum levels with side effect status.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a single-centre, retrospective study of adult patients with histoplasmosis receiving itraconazole therapy for at least 28\u2005days from 2002 to 2021. Reported side effects were characterized, and propensity score matching was used to compare itraconazole serum levels between patients with and without side effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Sixty-three out of 227 (27.8%) patients experienced at least one side effect, the most common of which were hepatotoxicity (7.0%), nausea\/vomiting (6.6%), and diarrhoea (6.2%). 12 (19.0%) patients with side effects underwent an itraconazole dose reduction and 29 (46.0%) had itraconazole discontinued. The median time to side effect was 45\u2005days. Median itraconazole serum levels were significantly higher among patients with side effects than in a propensity score-matched population without side effects (2.9 versus 1.8\u2005mcg\/mL, P\u200a=\u200a0.009).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Side effects were experienced by approximately one-quarter of patients with histoplasmosis receiving long-term itraconazole therapy. About two-thirds of these patients had a therapeutic intervention. Itraconazole resulted in a lower frequency of side effects than fluconazole, as measured in other studies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae437","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T02:15:43Z","timestamp":1733883343000},"page":"503-508","source":"Crossref","is-referenced-by-count":14,"title":["Side effects associated with itraconazole therapy"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5979-3311","authenticated-orcid":false,"given":"Matthew R","family":"Osborn","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine , 4523 Clayton Ave, MSC 8051-0043-15, St. Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio C","family":"Zuniga-Moya","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine , 4523 Clayton Ave, MSC 8051-0043-15, St. Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick B","family":"Mazi","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine , 4523 Clayton Ave, MSC 8051-0043-15, St. Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9555-2550","authenticated-orcid":false,"given":"Adriana M","family":"Rauseo","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine , 4523 Clayton Ave, MSC 8051-0043-15, St. Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7612-4710","authenticated-orcid":false,"given":"Andrej","family":"Spec","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine , 4523 Clayton Ave, MSC 8051-0043-15, St. Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"2025020223520172600_dkae437-B1","doi-asserted-by":"publisher","first-page":"e364","DOI":"10.1016\/S1473-3099(21)00191-2","article-title":"Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology","volume":"21","author":"Thompson","year":"2021","journal-title":"Lancet Infect Dis"},{"key":"2025020223520172600_dkae437-B2","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1086\/521259","article-title":"Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America","volume":"45","author":"Wheat","year":"2007","journal-title":"Clin Infect Dis"},{"key":"2025020223520172600_dkae437-B3","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1086\/588300","article-title":"Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America","volume":"46","author":"Chapman","year":"2008","journal-title":"Clin Infect Dis"},{"key":"2025020223520172600_dkae437-B4","doi-asserted-by":"publisher","first-page":"e112","DOI":"10.1093\/cid\/ciw360","article-title":"2016 Infectious Diseases Society of America (IDSA) clinical practice guideline for the treatment of coccidioidomycosis","volume":"63","author":"Galgiani","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2025020223520172600_dkae437-B5","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1093\/cid\/ciw326","article-title":"Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America","volume":"63","author":"Patterson","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2025020223520172600_dkae437-B6","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1086\/514744","article-title":"Itraconazole prophylaxis for fungal infections in patients with advanced human immunodeficiency virus infection: randomized, placebo-controlled, double-blind study. 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