| アブストラクト | BACKGROUND: Posaconazole, a broad-spectrum azole antifungal agent, is used for prophylaxis and treatment of invasive fungal infections (IFIs). However, it has been associated with pseudoaldosteronism-a syndrome involving hypertension, hypokalaemia, and QT prolongation-likely mediated by adrenal steroid biosynthesis inhibition. This study aimed to assess the association between posaconazole and pseudoaldosteronism using a triangulated approach integrating real-world pharmacovigilance data, clinical trial evidence, and a structured causality framework. METHODS: A disproportionality analysis of real-world pharmacovigilance data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) was performed to detect signals for pseudoaldosteronism, hypokalaemia, hypertension, and QT prolongation. Co-reported adverse events in pseudoaldosteronism cases were identified and counted. Clinical trial evidence was synthesised through a systematic review and meta-analysis (SR/MA) of randomised controlled trials comparing posaconazole with other antifungal agents. Causality was assessed based on the Bradford Hill criteria (BHC). RESULTS: In the FAERS analysis, posaconazole and itraconazole consistently showed signals for pseudoaldosteronism. Among reports of posaconazole, 29.8% (95% confidence interval [CI]: 22.1-38.4%) of pseudoaldosteronism cases co-occurred with hypokalaemia. The MA showed that posaconazole significantly increased the risk of hypokalaemia than did voriconazole (risk ratio: 10.41; 95% CI: 2.00-54.27; I(2) = 0%). Synthesizing our findings from the FAERS analysis and SR/MA supported a causal relationship based on the BHC. CONCLUSIONS: This study supports a causal association between posaconazole and pseudoaldosteronism by integrating clinical data from FAERS and SR/MA. Clinicians should closely monitor serum potassium during posaconazole therapy and consider pseudoaldosteronism in patients with hypokalaemia. |
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| ジャーナル名 | International journal of antimicrobial agents |
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| Pubmed追加日 | 2025/11/27 |
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| 投稿者 | Nakano, Yuki; Kotake, Kazumasa; Asai, Yuki; Murata, Masayuki; Uchiyama, Masanobu; Shimono, Nobuyuki; Hasuwa, Hirotsugu |
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| 組織名 | Department of Pharmacy, Saga University Hospital, Saga, Japan; Department of;Pharmacy, Saiseikai Futsukaichi Hospital, Fukuoka, Japan. Electronic address:;ynakano_1105@outlook.com.;Department of Pharmacy, Zikei Hospital/Zikei Institute of Psychiatry, Okayama,;Japan.;Department of Pharmacy, Mie University Hospital, Mie, Japan.;Department of Environmental Medicine and Infectious Disease, Kyushu University,;Fukuoka, Japan.;Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical;Sciences, Fukuoka University.;Department of General Internal Medicine, Kyushu University Hospital, Fukuoka,;Department of Pharmacy, Saiseikai Futsukaichi Hospital, Fukuoka, Japan. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/41297713/ |
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