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Adverse Effects Associated with Long-Term Administration of Azole Antifungal Agents

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Abstract

Azole antifungals are first-line options in the prophylaxis and treatment of invasive fungal infections. They are often used for prolonged (weeks to months) periods of time, particularly in patients with hematologic malignancies, or in those who have received a solid organ or hematopoietic stem cell transplant. Long-term use of azoles is associated with hepatotoxicity and hormone-related effects, including gynecomastia, alopecia, decreased libido, oligospermia, azoospermia, impotence, hypokalemia, hyponatremia, and (rarely) adrenal insufficiency. Voriconazole and posaconazole have been associated with peripheral neuropathies, and itraconazole and voriconazole with pancreatitis. In addition, voriconazole has been associated with periostitis, phototoxic reactions, and squamous cell carcinoma. Since many at-risk patients are commonly receiving multiple medications, it can be difficult for care providers to identify antifungal agent causality or contribution to patient symptoms. Knowledge and recognition of adverse events caused by azoles, leading to dose reduction or discontinuation, can generally reverse these adverse events.

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Authors and Affiliations

  1. Michigan Medicine, 1540 East Medical Center Dr. CW7-521B, Ann Arbor, MI, 48109, USA

    Lydia L. Benitez

  2. University of Michigan College of Pharmacy, 428 Church St., Ann Arbor, MI, 48109-1065, USA

    Peggy L. Carver

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  1. Lydia L. Benitez
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Peggy L. Carver, PharmD, FIDP has served as a consultant for Astellas. Lydia L. Benitez, PharmD, BCOP has no conflicts to disclose.

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Benitez, L.L., Carver, P.L. Adverse Effects Associated with Long-Term Administration of Azole Antifungal Agents. Drugs 79, 833–853 (2019). https://doi.org/10.1007/s40265-019-01127-8

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