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
- Dose reductions are required in severe renal insufficiency (see Dosing Guidelines)
- Fluconazole can inhibit the hepatic metabolism of many other drugs via CYP 450 enzymes: screen for drug interactions
- Pregnancy and breastfeeding - for safety information, see Table on Safety of Anti-infective therapy in Pregnancy & Lactation
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