Fluconazole-Associated Hypercalcemia in Patients with Coccidioidomycosis

Abstract

Fluconazole, voriconazole, and itraconazole may potentiate the hypercalcemic effect of other medications, although to date, triazoles alone have not been linked to hypercalcemia. We describe a case of new-onset hypercalcemia in the setting of high-dose fluconazole that resolved after changing the antifungal regimen. We reviewed our institutional database to assess the frequency of moderate or severe hypercalcemia (serum calcium ≥12 mg/dL) among patients with coccidioidomycosis treated with a triazole. We identified 2,133 patients, seen from January 1, 2005, through December 20, 2012, with a diagnosis of coccidioidomycosis. Twenty-three patients (1%) had subsequent hypercalcemia; of these, 20 patients (87%) had moderate or severe hypercalcemia. Nine of the 20 patients (45%) with moderate or severe hypercalcemia were taking triazoles, and most had comorbid conditions that were risk factors for hypercalcemia (tertiary hyperparathyroidism, n=4; multiple myeloma, n=2; adrenal insufficiency, n=1). The effect of fluconazole on calcium metabolism possibly is small or not clinically significant until the dose is high. Fluconazole may also contribute to hypercalcemia in patients with underlying hyperparathyroidism because of the loss of calcium's inhibitory effect on parathyroid hormone secretion. In summary, moderate or severe hypercalcemia is uncommon in coccidioidomycosis and rare in those treated with triazoles. High-dose fluconazole may be associated with symptomatic hypercalcemia, especially in patients with predisposing comorbid conditions.

Case Report: Hypercalcemia as a manifestation of acute adrenal crisis precipitated by fluconazole use, and a review of the literature

“…There have been case reports of hypercalcemia occurring with azole antifungal use, although cortisol levels were not measured, and it is unclear whether hypocortisolism may have contributed to hypercalcemia ( 36 , 37 ). The authors postulated that hypercalcemia may have occurred due to inhibition of CYP enzymes responsible for the metabolism of vitamin A or via PTH-mediated hypercalcemia.…”

Negative cerebrospinal fluid β-d-glucan levels as an indicator for treatment cessation ahead of biochemical resolution: A case report of Candida glabrata meningitis

“…Triazole-associated hypercalcemia is rare. A case report of symptomatic hypercalcemia associated with high-dose fluconazole has been published in the literature [ 10 ]. Our patient developed new-onset hypercalcemia after more than a month of fluconazole therapy, during which no new medication was introduced throughout this period.…”