What is the recommended dose of fluconazole (an antifungal medication) for an adult patient with moderate to severe fungal infection, considering potential impaired liver or kidney function?

Fluconazole Dosing Recommendations

For moderate to severe fungal infections in adults, fluconazole should be initiated with an 800 mg (12 mg/kg) loading dose on day 1, followed by 400 mg (6 mg/kg) daily, with dose adjustments required for impaired renal function but not for hepatic dysfunction. 1

Dosing by Infection Type and Severity

Candidemia and Invasive Candidiasis

• Loading dose: 800 mg (12 mg/kg) on day 1 1
• Maintenance: 400 mg (6 mg/kg) daily for at least 14 days after first negative blood culture and resolution of symptoms 1
• Duration: Continue for 2 weeks after documented clearance of bloodstream infection 1

Oropharyngeal and Esophageal Candidiasis

• Mild disease: 100-200 mg daily for 7-14 days 1
• Moderate to severe disease: 200-400 mg (3-6 mg/kg) daily for 14-21 days 1
• For esophageal candidiasis specifically, the higher end of this range (400 mg daily) is preferred 1

Urinary Tract Candidiasis

• Cystitis (fluconazole-susceptible): 200-400 mg (3-6 mg/kg) daily for 2 weeks 1, 2
• Pyelonephritis: 200-400 mg (3-6 mg/kg) daily for 2 weeks 1, 2
• For fluconazole-resistant organisms (C. glabrata, C. krusei), amphotericin B deoxycholate 0.3-0.6 mg/kg daily is recommended instead 1

Cryptococcal Meningitis

• Initial therapy: 400-1200 mg orally daily (typically 400 mg for most patients) 1
• Consolidation: 400-600 mg daily for 8 weeks 1
• Maintenance: 200 mg (3 mg/kg) daily for 6-12 months 1

Renal Function Adjustments

Critical dosing modification required for impaired kidney function:

• CrCl >50 mL/min: No adjustment needed - use 100% of standard dose 2, 3
• CrCl ≤50 mL/min (no dialysis): Reduce maintenance dose to 50% of standard dose after loading dose 2, 3
• Hemodialysis patients: Administer 100% of recommended dose after each dialysis session (typically 400 mg post-HD for serious infections, 3 times weekly) 4, 3
• Loading dose: Always give full loading dose regardless of renal function (50-400 mg depending on indication) 3

The FDA label specifies that when serum creatinine is the only measure available, use the Cockcroft-Gault equation to estimate creatinine clearance for dosing adjustments 3.

Hepatic Function Considerations

No dose adjustment is required for hepatic impairment - fluconazole is primarily renally eliminated with approximately 80% excreted unchanged in urine 3. However, monitor liver enzymes as elevations can occur during treatment 5.

Common Pitfalls to Avoid

• Underdosing in serious infections: The 400 mg daily maintenance dose is necessary for invasive candidiasis; lower doses (200 mg) are only appropriate for less severe infections like uncomplicated cystitis 4
• Assuming all Candida species are susceptible: C. krusei is intrinsically resistant to fluconazole, and C. glabrata often has reduced susceptibility - obtain susceptibility testing and consider alternative agents (amphotericin B or echinocandins) for these organisms 1, 4
• Forgetting the loading dose: The loading dose (typically double the maintenance dose) is essential to rapidly achieve therapeutic concentrations, particularly in critically ill patients 1, 4
• Inadequate duration: Premature discontinuation leads to relapse - continue for at least 14 days after documented clearance for candidemia 1
• Overlooking renal dosing: Fluconazole accumulates significantly in renal impairment; failure to adjust can lead to toxicity 2, 3

Special Populations

Hemodialysis Patients with Wound Infections

• Day 1: 800 mg (12 mg/kg) loading dose 4
• Maintenance: 400 mg (6 mg/kg) after each hemodialysis session (3 times weekly for standard intermittent HD) 4
• Duration: Continue for at least 2 weeks after clinical resolution; extend for deep tissue involvement based on clinical response 4
• Essential adjunct: Ensure adequate source control with debridement of necrotic tissue and drainage of collections 4

Elderly Patients

• Pharmacokinetic studies show higher AUC and longer half-life (46.2 hours vs. 30 hours in younger adults) due to age-related decline in renal function 3
• Adjust dosing based on creatinine clearance rather than age alone 3

High-Dose Therapy Considerations

For refractory or severe infections, doses up to 800-1600 mg daily have been studied and show dose-dependent responses with acceptable safety profiles 6. However, a maximum daily dose of 1600 mg is recommended to avoid neurological toxicity 7. These higher doses should be reserved for life-threatening infections with documented or suspected resistant organisms 6.