Posaconazole Serum Drug Levels Associated With Pseudohyperaldosteronism

Abstract

Background: Posaconazole tablets are well tolerated and efficacious in the prophylaxis and treatment of aspergillosis, mucormycosis, and other invasive fungal infections. There have been case reports of posaconazole-induced pseudohyperaldosteronism (PIPH); however, its occurrence and association with serum posaconazole drug levels have not previously been investigated.

Methods: In this single-center, retrospective, observational study, we examined the occurrence of PIPH in outpatients newly starting posaconazole and evaluated differences in serum posaconazole concentrations 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 = .007) and more frequently had hypertension prior to starting posaconazole (68.8% vs 32.1%, P = .009). Patients with PIPH had a significantly higher median serum posaconazole level than those without PIPH (3.0 vs 1.2 µg/mL, P ≤ .0001). There was a positive correlation between serum posaconazole levels and changes in systolic blood pressure (r = .37, P = .01), a negative correlation between serum posaconazole levels and changes in serum potassium (r = -.39, P = .006), and a positive correlation between serum posaconazole levels and serum 11-deoxycortisol (r = .69, P < .0001).

Conclusions: 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.

Keywords: hypertension; hypokalemia; therapeutic drug monitoring; toxicity; triazole.