Management of posaconazole-induced pseudohyperaldosteronism

Author:

Davis Matthew R1ORCID,Nguyen Minh-Vu H2,Gintjee Thomas J3,Odermatt Alex4,Young Brian Y5,Thompson George R267

Affiliation:

1. Department of Pharmacy, University of California Los Angeles Ronald Reagan Medical Center, Los Angeles, CA, USA

2. Department of Internal Medicine, Division of Infectious Diseases, University of California–Davis Health, Sacramento, CA, USA

3. Department of Pharmacy, University of California–Davis Health, Sacramento, CA, USA

4. Swiss Centre for Applied Human Toxicology and Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland

5. Department of Internal Medicine, Division of Nephrology, University of California–Davis Health, Sacramento, CA, USA

6. Department of Medical Microbiology and Immunology, University of California–Davis Health, Sacramento, CA, USA

7. University of California–Davis Center for Valley Fever, Davis, CA, USA

Abstract

Abstract Background Posaconazole-induced pseudohyperaldosteronism (PIPH) has been associated with elevated posaconazole serum concentrations. Clinicians are faced with the difficult task of managing patients with PIPH while maintaining the efficacy of antifungal therapy. Commonly, modifications to posaconazole therapy are utilized in managing PIPH, including dosage reduction of posaconazole or switch to an alternative antifungal. Objectives To characterize the management of patients diagnosed with PIPH and their response to various therapeutic interventions. Methods We retrospectively reviewed 20 consecutive adult patients diagnosed with PIPH. Patient data collected included blood pressure, electrolytes, endocrine laboratory values and posaconazole serum concentrations collected before and after therapeutic intervention. Results Of 20 patients included, 17 patients (85%) underwent therapeutic modification, with posaconazole dose reduction (n = 11) as the most common change. Other modifications included discontinuation (n = 3), switch to an alternative antifungal (n = 2) and addition of spironolactone (n = 1). Clinical improvement (decrease in systolic blood pressure and increase in serum potassium) was observed in 9 of 17 patients (52.9%). An average decrease in systolic blood pressure of 7.1 mmHg and increase in serum potassium of 0.22 mmol/L was observed following therapeutic modification. Conclusions We report our experience with PIPH management, for which there is no universally effective strategy. We utilized a stepwise approach for management, starting with posaconazole dose reduction and repeat assessment of clinical and laboratory parameters. If resolution of PIPH is not achieved, an alternative triazole antifungal or the addition of an aldosterone antagonist are additional potential interventions. It is possible for PIPH to persist after therapeutic modification despite these interventions. Thus, early diagnosis and continuous monitoring is warranted.

Funder

Swiss Centre for Applied Human Toxicology

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)

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