What are the recommended fluconazole dosing regimens for adults and children for different infections, and how should the dose be adjusted in renal impairment?

Fluconazole Dosing Recommendations

For adults with invasive candidiasis or candidemia, administer a loading dose of 800 mg (12 mg/kg) on day 1, followed by 400 mg (6 mg/kg) daily, with dose reduction to 50% of the maintenance dose (200 mg daily after the loading dose) required when creatinine clearance falls below 50 mL/min. 1, 2

Standard Adult Dosing by Indication

Invasive Candidiasis and Candidemia

• Loading dose: 800 mg (12 mg/kg) IV or PO on day 1 1, 2
• Maintenance dose: 400 mg (6 mg/kg) daily 1, 2
• Duration: Minimum 14 days after first negative blood culture and resolution of symptoms 1, 2
• Remove all intravascular catheters whenever feasible 2

Esophageal Candidiasis

• Dose: 200–400 mg (3–6 mg/kg) daily 1, 2
• Duration: 14–21 days 1, 2
• For moderate-to-severe disease, use 400 mg daily 2

Oropharyngeal Candidiasis

• Mild disease: 100–200 mg daily for 7–14 days 1
• Moderate-to-severe disease: 100–200 mg daily for 7–14 days 1, 2

Urinary Tract Candidiasis

• Symptomatic cystitis: 200 mg (3 mg/kg) daily for 14 days 1
• Pyelonephritis: 200–400 mg (3–6 mg/kg) daily for 14 days 1
• Fluconazole achieves urinary concentrations 10–20 times serum levels, making it ideal for urinary infections 1, 3

Cryptococcal Meningitis

• Consolidation phase: 400–800 mg daily for 8 weeks 4, 5
• Maintenance/suppression (AIDS patients): 200 mg daily 5

Renal Dose Adjustments

The critical threshold for dose reduction is creatinine clearance ≤50 mL/min, NOT 60 mL/min—this is a common prescribing error. 2, 3

Dosing Algorithm by Renal Function

CrCl >50 mL/min:

• No adjustment needed; use standard dosing based on indication 2, 3, 5

CrCl ≤50 mL/min (not on dialysis):

• Administer full loading dose on day 1 2, 3, 5
• Reduce maintenance dose to 50% starting day 2 2, 3, 5
• Example: For invasive candidiasis, give 800 mg day 1, then 200 mg daily thereafter 2

Hemodialysis patients:

• Administer 100% of recommended dose after each dialysis session 2, 3, 5
• For serious infections: 400 mg post-HD, typically 3 times weekly 2
• On non-dialysis days, give reduced dose according to CrCl 3, 5
• Approximately 50% of fluconazole is removed during a 3-hour hemodialysis session 3

Pharmacokinetic Rationale

Fluconazole is cleared primarily by renal excretion as unchanged drug (>90% excreted unchanged in urine), and renal clearance decreases proportionally with declining CrCl 2, 3. The elimination half-life is approximately 30 hours in normal renal function but becomes prolonged in renal impairment 3, 6.

Pediatric Dosing

Standard Pediatric Dosing Equivalents

The following weight-based doses provide equivalent exposure to adult fixed doses 5:

• 3 mg/kg (pediatric) ≈ 100 mg (adult) 5
• 6 mg/kg (pediatric) ≈ 200 mg (adult) 5
• 12 mg/kg (pediatric) ≈ 400 mg (adult) 5

Age-Specific Considerations

Neonates (first 2 weeks of life):

• Use same mg/kg dose as older children but administer every 72 hours due to prolonged half-life 4, 5
• After 2 weeks: transition to once-daily dosing 5

Children >1 year with life-threatening infections:

• May require 6 mg/kg every 12 hours due to more rapid clearance 4

Pediatric Dosing by Indication

Oropharyngeal candidiasis:

• 6 mg/kg loading dose day 1, then 3 mg/kg daily for ≥2 weeks 5

Esophageal candidiasis:

• 6 mg/kg loading dose day 1, then 3 mg/kg daily (up to 12 mg/kg/day based on response) 5
• Minimum 3 weeks and ≥2 weeks after symptom resolution 5

Systemic Candida infections:

• 6–12 mg/kg/day 5

Cryptococcal meningitis:

• 12 mg/kg loading dose day 1, then 6 mg/kg daily (up to 12 mg/kg based on response) 5
• Duration: 10–12 weeks after CSF culture negative 5

Pediatric renal impairment:

• Dosage reduction should parallel adult recommendations 5
• Use formula: K × height (cm) / serum creatinine (mg/100 mL), where K=0.55 for children >1 year and 0.45 for infants 5

Route of Administration

Oral and IV formulations are therapeutically equivalent with >90% bioavailability. 1, 2

• Switch to oral therapy as soon as patient can tolerate oral intake 2
• Absorption not affected by food, gastric pH, or disease state 1
• Can be taken with or without food 5

IV infusion rate: ≤200 mg/hour 2

Critical Species Considerations

Candida krusei is intrinsically resistant to fluconazole—use an alternative agent (amphotericin B or echinocandin). 1, 2

Candida glabrata may have reduced susceptibility and require higher doses or alternative therapy 2

Common Pitfalls to Avoid

1. Do NOT reduce dose at CrCl 60 mL/min—the threshold is 50 mL/min 2, 3
2. Always give full loading dose even in renal impairment—only reduce maintenance dosing 2, 3
3. Never confuse prophylaxis dosing with treatment dosing—prophylaxis regimens (typically 100–400 mg daily) are inadequate for active infections requiring 6–12 mg/kg daily 1, 4
4. Do NOT use IV voriconazole (contains cyclodextrin) in CrCl <50 mL/min—fluconazole is safer in this setting 1
5. Remember to adjust concomitant medications—fluconazole inhibits CYP3A4 and CYP2C9, affecting cyclosporine, phenytoin, warfarin, and oral hypoglycemics 3

Monitoring Recommendations

• Perform dilated retinal examination within first week for all candidemia patients 2
• Monitor renal function regularly during therapy, as changes in CrCl may necessitate dose adjustments 3
• For cryptococcal infections, document CSF culture clearance after 2 weeks of induction 4

Special Populations

Breastfeeding mothers: Can safely continue nursing while taking fluconazole without interruption 4

Transplant recipients: Fluconazole clearance may be further reduced due to concurrent calcineurin inhibitors affecting renal function 4