Fluconazole

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