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732. Posaconazole Serum Drug Levels Associated with Pseudohyperaldosteronism

BACKGROUND: Posaconazole is an extended-spectrum triazole used in the treatment and prophylaxis of many fungal diseases. There have been case reports of posaconazole-induced pseudohyperaldosteronism; however, its occurrence and association with serum posaconazole drug levels need further investigati...

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Detalles Bibliográficos
Autores principales: Nguyen, Minh-Vu Hoang, Davis, Matthew R, Wittenberg, Rebecca, Mchardy, Ian, Baddley, John W, Young, Brian, Odermatt, Alex, Thompson, George R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810883/
http://dx.doi.org/10.1093/ofid/ofz360.800
Descripción
Sumario:BACKGROUND: Posaconazole is an extended-spectrum triazole used in the treatment and prophylaxis of many fungal diseases. There have been case reports of posaconazole-induced pseudohyperaldosteronism; however, its occurrence and association with serum posaconazole drug levels need further investigation. METHODS: In this single-center retrospective observational study, we examined the occurrence of posaconazole-induced pseudohyperaldosteronism (PIPH), diagnosed either clinically or via laboratory abnormalities, and evaluated differences in serum posaconazole concentration and clinical characteristics between those with and without this syndrome. RESULTS: Sixty-nine patients receiving posaconazole were included; of whom, 16 (23.2%) met the definition of PIPH. Patients with PIPH were significantly older (61.1 vs. 44.7 years, P = 0.007), more frequently had hypertension prior to starting posaconazole (68.8% vs. 32.1%, P = 0.009), and were more frequently prescribed posaconazole for active treatment instead of prophylaxis compared with patients without PIPH (62.5% vs. 24.5%, P = 0.005). Patients with PIPH had a significantly higher median serum posaconazole level than those without PIPH (3.0 vs. 1.2 µg/mL, P = 0.0001). There was a positive correlation between serum posaconazole level and change in systolic blood pressure (r = 0.37, P = 0.01), a negative correlation between serum posaconazole level and change in serum potassium (r = −0.39, P = 0.006), and a positive correlation between serum posaconazole level and serum 11-deoxycortisol (r = 0.69, P < 0.0001). CONCLUSION: Posaconazole is associated with secondary hypertension and hypokalemia, consistent with pseudohyperaldosteronism, and development is associated with higher serum posaconazole concentrations, older age, and baseline hypertension. Management may include dose reduction, the addition of an aldosterone antagonist, or an alternative triazole agent. [Image: see text] [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.