International journal of antimicrobial agents · 2025
Adverse effects of posaconazole on adrenal steroid biosynthesis: An integrative approach using FAERS-based pharmacovigilance and systematic review with meta-analysis of randomised controlled trials.
СтатьяСистематический обзорМетаанализНазвание и аннотация: Перевод в очереди
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Nakano Yuki, Kotake Kazumasa, Asai Yuki, Murata Masayuki, Uchiyama Masanobu, Shimono Nobuyuki, Hasuwa Hirotsugu
Аннотация
OBJECTIVES: Posaconazole, a broad-spectrum azole antifungal agent, is used for prophylaxis and treatment of invasive fungal infections. 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; I2 = 0%). Synthesising 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.
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; I2 = 0%). Synthesising 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.