Tolerability of long-term fluconazole therapy

Matthew R. Davis, Minh Vu H. Nguyen, Monica A. Donnelley, George R. Thompson

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Background: Fluconazole is a commonly prescribed first-generation triazole antifungal. Although the toxicity profile of fluconazole has been evaluated in clinical trials, there are scant data regarding its tolerability with longterm therapy. Treatment guidelines for coccidioidomycosis recommend fluconazole therapy and severe or disseminated infections can require lifelong treatment. Objectives: To assess the prevalence of long-term fluconazole adverse effects, their consequences for antifungal therapy, time to adverse effects and the association between dosing regimen or fluconazole serum level and adverse effect status. Methods: We conducted a single-centre, retrospective study of adult patients (≥18 years) with proven or probable coccidioidomycosis receiving long-term fluconazole therapy for an intended duration of≥28 days. Results: Out of 124 patients included, 64 (51.6%) experienced adverse effects. The most common adverse effects were xerosis (16.9%), alopecia (16.1%) and fatigue (11.3%). Of the 64 patients experiencing adverse effects, 42 (65.6%) required a therapeutic intervention such as dose reduction, discontinuation or switch to a new antifungal. Patients experiencing adverse effects were prescribed higher total daily fluconazole doses (6.7 versus 5.7 mg/kg; P<0.01). The median therapeutic drug levels did not differ significantly between patients who experienced adverse effects and those who did not (36.1 versus 28.1 mg/L; P=0.35). Conclusions: A significant number of patients receiving long-term fluconazole therapy for coccidioidomycosis experienced adverse effects. Of these, around two-thirds required a therapeutic change. We believe these findings are representative of the adverse effect profile of long-term fluconazole therapy as it is used in clinical practice for coccidioidomycosis as opposed to use in clinical trials.

Original languageEnglish (US)
Pages (from-to)768-771
Number of pages4
JournalJournal of Antimicrobial Chemotherapy
Issue number3
StatePublished - Mar 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)


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