Background
- Antifungal in the triazole family with excellent bioavadilability but limited efficacy outside of Candida
Pharmacokinetics and Pharmacodynamics
- Good oral bioavailability
- Good CNS penetration
- Fungistatic
- Efficacy predicted by AUC/MIC ratio
Clinical Breakpoints
| Species | ECV (μg/mL) | Breakpoints (μg/mL) | Breakpoints (mm) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| S | SDD | I | R | S | SDD | I | R | ||
| Candida albicans | 0.5 | ≤2 | 4 | — | ≥8 | ≥17 | 14-16 | — | ≤13 |
| Candida dubliniensis | 0.5 | ||||||||
| Candida glabrata | 8 | — | ≤32 | — | ≥64 | — | ≥15 | — | ≤14 |
| Candida guilliermondii | 8 | ||||||||
| Candida krusei | intrinsically resistant | intrinsically resistant | |||||||
| Candida lusitaniae | 1 | ||||||||
| Candida parapsilosis | 1 | ≤2 | 4 | — | ≥8 | ≥17 | 14-16 | — | ≤13 |
| Candida tropicalis | 1 | ≤2 | 4 | — | ≥8 | ≥17 | 14-16 | — | ≤13 |
| Cryptococcus neoformans | 8 | ||||||||
| Cryptococcus gattii | 16-32 | ||||||||
Dosing
- Invasive candidiasis: fluconazole 6 to 12 mg/kg PO/IV q24h
- Candidemia: 12 mg/kg IV load followed by 6 mg/kg PO/IV daily
- Can use 800 mg daily for isolates that show dose-dependent susceptibility
- Vaginal candidiasis: 150 mg PO once, with or without intravaginal clotrimazole
- Oral thrush: 100 mg po daily for 7 to 14 days
- Esophageal candidiasis: 200 mg PO daily for 14 to 21 days
- Urinary tract infection: 200 mg po daily for 7 to 14 days
- Intraabdominal infection: 400 mg PO daily
Monitoring
- ECG for QT prolongation
- Liver enzymes for hepatitis
Adverse Drug Reactions
- Best side effect profiles of the antifungals
- Before starting, check:
- Liver enzymes as baseline (hepatitis)
- Creatinine (requires renal dosing)
- EKG (QTc prolongation)
- Beware drug-drug interactions, especially with new DOACs
