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Antimicrobials

Fluconazole

Guidelines for use

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1. Spectrum of Activity

Active against:

  • Candida species: C. albicans, C. glabrata (dose-dependent sensitivity), C. parapsilosis (may demonstrate dose-dependent susceptibility), C. tropicalis, C. dubliniensis, C. guilliermondii
  • Cryptococcus species
  • Dimorphic Fungi (Blastomyces, Coccidiodes)

Not active against:

  • Candida krusei (intrinsic resistance)
  • Aspergillus species
  • Zygomycetes

2. Clinical use

  • Treatment of systemic candidiasis (where fluconazole-susceptible)
  • Treatment of severe mucocutaneous candidiasis
  • Treatment of blastomycosis, coccidiodomycosis or cryptococcal fungal infections (consult Infectious Diseases)

3. Precautions

4. Adverse Effects

  • Nausea, vomiting, diarrhea, abdominal pain
  • Elevation of transaminases; hepatotoxicity is rare.
  • QT prolongation (increased risk with concomitant use of other QT-prolonging agents)
  • Alopecia with doses ≥ 400mg daily after median of 3 months treatment

5. Dosage

Note:
The oral bioavailability of oral fluconazole is > 90%.
IV therapy should be reserved for patients with impaired gut absorption or for those unable to swallow.

  • Empiric therapy (Candidemia): 800 mg PO Q24H until species confirmed:
    • C. albicans, C. tropicalis, C. dubliniensis: 400 mg PO Q24H
    • C. glabrata & C. parapsilosis*: 800 mg PO Q24H

*for C. parapsilosis: may decrease dose to 400 mg PO Q24H if full sensitivity to fluconazole is confirmed. Maintain dose of 800 mg PO Q24H if fluconazole susceptibility is dose-dependent

  • Esophageal candidiasis: 200 – 400 mg PO Q24H
  • Vaginal candidiasis: 150 mg PO x 1 dose

Renal insufficiency:

CREATININE CLEARANCE (mL/min) FLUCONAZOLE DOSAGE
10 to 29 Usual dose Q48H
< 10 (ESRD; PD) Usual dose Q48H
Hemodialysis (HD)

Usual dose 3 times per week towards the end of HD. (None on non-dialysis days).

Continous Renal Replacement Therapy (CRRT) 600 mg q24h

6. Monitoring

  • Baseline LFTs, QTc, serum creatinine (for dosing considerations)
  • Periodic LFT assessment, QTc and serum creatinine (for dosing considerations) throughout therapy

Last updated: April 8, 2019