{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:59:38Z","timestamp":1790913578729,"version":"4.1.0"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Invasive aspergillosis (IA) poses significant mortality risks, particularly in immunocompromised patients. The safety profiles of FDA-approved antifungal agents, triazoles (Voriconazole, Posaconazole, Isavuconazole), polyenes (Amphotericin B), and echinocandins (Caspofungin), are not yet fully characterized in real-world settings. This study employed pharmacovigilance data to systematically evaluate the comparative safety profiles of these agents, providing evidence-based insights for clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective analysis of the FDA Adverse Event Reporting System (FAERS) data (2004Q1\u20132024Q3) was conducted. Disproportionality analyses, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma-Poisson Shrinker (MGPS), were employed to identify adverse event (AE) signals. Duplicate entries were identified and removed using CASE_ID and FDA_DT criteria, after which AE signals were classified according to MedDRA System Organ Classes (SOCs) and Preferred Terms (PTs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 26,004 antifungal-associated AE reports, Amphotericin B exhibited the strongest renal toxicity signals (nephropathy toxic (i.e., nephrotoxicity): ROR = 24.86; renal tubular disorder: ROR = 46.46), while voriconazole was associated with hepatobiliary disorders (ROR = 4.61) and ocular toxicity (toxic optic neuropathy: ROR = 228.80). Caspofungin demonstrated marked hepatotoxicity (cholestasis: ROR = 23.79), whereas Posaconazole and Isavuconazole showed lower mortality rates (19.56% and 22.70%, respectively). Amphotericin B demonstrated the highest mortality rate (47.14%), which was statistically significantly higher compared to other agents (\u03c7\n                      <jats:sup>2<\/jats:sup>\n                      test, p &amp;lt; 0.001), and life-threatening AE rates (4.97%), contrasting with Isavuconazole\u2019s favorable safety profile (1.89% life-threatening AEs). Time-to-onset analysis revealed delayed AE onset for Isavuconazole (median: 19.5\u00a0days) versus Caspofungin (6\u00a0days).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Significant safety variations exist among antifungal agents for IA. Amphotericin B and Caspofungin are associated with severe renal\/hepatic toxicities and higher mortality, while Isavuconazole and Posaconazole may offer safer alternatives with delayed AE onset. Clinicians should prioritize drug-specific risks when tailoring treatment for IA patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1718019","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:52:56Z","timestamp":1767768776000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacovigilance insights: safety profiles of antifungal agents for invasive aspergillosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Wei","family":"Jia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiezhou","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingru","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1007\/s11046-023-00727-z","article-title":"Treatment of invasive aspergillosis: how it's going, where it's heading","volume":"188","author":"Boyer","year":"2023","journal-title":"Mycopathologia"},{"key":"B2","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.idc.2015.10.015","article-title":"Invasive aspergillosis: current strategies for diagnosis and management","volume":"30","author":"Cadena","year":"2016","journal-title":"Infect. Dis. Clin. North Am."},{"key":"B3","first-page":"244","article-title":"Characteristics of amphotericin B-induced endothelial cell injury","volume":"121","author":"Cutaia","year":"1993","journal-title":"J. Lab. Clin. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.ijantimicag.2014.05.019","article-title":"Voriconazole pharmacokinetics and exposure-response relationships: assessing the links between exposure, efficacy and toxicity","volume":"44","author":"Dolton","year":"2014","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B5","doi-asserted-by":"publisher","first-page":"324","DOI":"10.3390\/jof6040324","article-title":"Isavuconazole: mechanism of action, clinical efficacy, and resistance","volume":"6","author":"Ellsworth","year":"2020","journal-title":"J. Fungi (Basel)"},{"key":"B6","volume-title":"FDA regional implementation guide for E2b(R3) electronic transmission of individual case safety reports for drug and biological products: guidance for industry","year":"2024"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3569","DOI":"10.2174\/13816128113199990330","article-title":"Invasive aspergillosis: new insights into disease, diagnostic and treatment","volume":"19","author":"Karthaus","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"B8","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/s1368-7646(03)00064-5","article-title":"Caspofungin: the first in a new class of antifungal agents","volume":"6","author":"Kartsonis","year":"2003","journal-title":"Drug Resist Updat"},{"key":"B9","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.medcli.2024.01.045","article-title":"Invasive aspergillosis: a comprehensive review","volume":"163","author":"Machado","year":"2024","journal-title":"Med. Cl\u00edn. (English Edition)"},{"key":"B10","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/S0140-6736(15)01159-9","article-title":"Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by aspergillus and other filamentous fungi (secure): a phase 3, randomised-controlled, non-inferiority trial","volume":"387","author":"Maertens","year":"2016","journal-title":"Lancet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2196\/medinform.3022","article-title":"Automatically recognizing medication and adverse event information from food and drug administration's adverse event reporting system narratives","volume":"2","author":"Polepalli Ramesh","year":"2014","journal-title":"JMIR Med. Inf."},{"key":"B12","doi-asserted-by":"publisher","first-page":"94","DOI":"10.2165\/00002018-199005020-00003","article-title":"Amphotericin B nephrotoxicity drug safety","volume":"5","author":"Sabra","year":"1990","journal-title":"Drug Saf."},{"key":"B13","doi-asserted-by":"publisher","first-page":"796","DOI":"10.7150\/ijms.6048","article-title":"Data mining of the public version of the FDA adverse event reporting system","volume":"10","author":"Sakaeda","year":"2013","journal-title":"Int. J. Med. Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1034\/j.1399-3062.1999.010406.x","article-title":"Amphotericin B and its new formulations: pharmacologic characteristics, clinical efficacy, and tolerability","volume":"1","author":"Tiphine","year":"1999","journal-title":"Transpl. Infectious Dis."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e0007423","DOI":"10.1128\/mbio.00074-23","article-title":"Caspofungin-induced \u0392(1,3)-glucan exposure in Candida albicans is driven by increased chitin levels","volume":"14","author":"Wagner","year":"2023","journal-title":"mBio"},{"key":"B16","doi-asserted-by":"publisher","first-page":"164","DOI":"10.3389\/fcimb.2020.00164","article-title":"Caspofungin induced cell wall changes of candida species influences macrophage interactions","volume":"10","author":"Walker","year":"2020","journal-title":"Front. Cell Infect. Microbiol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1718019\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:52:57Z","timestamp":1767768777000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1718019\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":16,"alternative-id":["10.3389\/fphar.2025.1718019"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1718019","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]},"article-number":"1718019"}}