Tolerability of long-term fluconazole therapy

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 long-term 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
JournalThe Journal of antimicrobial chemotherapy
Volume74
Issue number3
DOIs
StatePublished - Mar 1 2019

Fingerprint

Fluconazole
Coccidioidomycosis
Therapeutics
Clinical Trials
Triazoles
Alopecia
Fatigue
Retrospective Studies
Guidelines

ASJC Scopus subject areas

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

Cite this

Tolerability of long-term fluconazole therapy. / Davis, Matthew R.; Nguyen, Minh Vu H.; Donnelley, Monica A.; Thompson, George Richard.

In: The Journal of antimicrobial chemotherapy, Vol. 74, No. 3, 01.03.2019, p. 768-771.

Research output: Contribution to journalArticle

Davis, Matthew R. ; Nguyen, Minh Vu H. ; Donnelley, Monica A. ; Thompson, George Richard. / Tolerability of long-term fluconazole therapy. In: The Journal of antimicrobial chemotherapy. 2019 ; Vol. 74, No. 3. pp. 768-771.
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AB - 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 long-term 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.

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