What is the recommended dose of fluconazole (an antifungal medication) for an adult patient with normal renal function and impaired renal function, respectively?

Fluconazole Dosing Recommendations

Standard Dosing in Adults with Normal Renal Function

For invasive candidiasis and candidemia, initiate fluconazole with an 800 mg (12 mg/kg) loading dose on day 1, followed by 400 mg (6 mg/kg) daily. 1, 2

Dosing by Indication (Normal Renal Function):

• Candidemia/Invasive Candidiasis: 800 mg loading dose, then 400 mg daily for at least 14 days after first negative blood culture and symptom resolution 1, 2

• Oropharyngeal Candidiasis:

  • Mild disease: 100-200 mg daily for 7-14 days 1, 3
  • Moderate to severe disease: 100-200 mg daily for 7-14 days 4, 3

• Esophageal Candidiasis: 200-400 mg (3-6 mg/kg) daily for 14-21 days 4

• Urinary Tract Candidiasis:

  • Cystitis: 200 mg (3 mg/kg) daily for 2 weeks 1, 4
  • Pyelonephritis: 200-400 mg (3-6 mg/kg) daily for 2 weeks 1, 4

• Cryptococcal Meningitis:

  • Consolidation: 400-600 mg daily for 8 weeks 1
  • Maintenance: 200 mg (3 mg/kg) daily for 6-12 months 1

• C. glabrata Infections: 800 mg (12 mg/kg) daily for fluconazole-susceptible isolates only 1

Dosing Adjustments for Impaired Renal Function

After administering the full loading dose (50-400 mg depending on indication), reduce the maintenance dose to 50% of the standard dose for patients with creatinine clearance ≤50 mL/min who are not on dialysis. 1, 2, 5

Specific Renal Dosing Algorithm:

• CrCl >50 mL/min: 100% of standard dose (no adjustment needed) 5

• CrCl ≤50 mL/min (no dialysis):

  • Give full loading dose initially 5
  • Then 50% of standard maintenance dose 1, 2, 5
  • Example: If standard dose is 400 mg daily, give 200 mg daily 4

• Hemodialysis Patients:

  • Give 100% of recommended dose after each hemodialysis session 2, 5
  • For serious infections: 400 mg post-HD, typically 3 times weekly 2
  • Loading dose: 800 mg (12 mg/kg) on day 1, then 400 mg (6 mg/kg) after each HD session 2
  • On non-dialysis days, use reduced dosing per CrCl 5

• Continuous Renal Replacement Therapy (CRRT):

  • 800 mg daily is recommended due to high extracorporeal clearance 6, 7
  • CVVHD clearance exceeds that of healthy individuals, requiring higher doses 7
  • Maintenance dose should be multiplied by factor of 3.8 for CAVHD/CVVHD with combined dialysate/ultrafiltrate flow of 1.5 L/h 7

Critical Considerations for Renal Dosing:

• No adjustment needed for single-dose vaginal candidiasis therapy regardless of renal function 5

• Loading doses should always be given at full strength before implementing renal dose reductions 5

• Therapeutic drug monitoring is recommended for life-threatening infections in patients on CRRT to ensure adequate plasma levels (target 4-20 mcg/mL) 7

• Fluconazole is cleared ~50% by a 3-hour hemodialysis session, necessitating post-dialysis dosing 5

Important Clinical Pitfalls

• Do not reduce loading doses in renal impairment—only maintenance doses require adjustment 5

• ICU patients with normal renal function may require higher doses (600 mg daily) due to increased clearance 6

• Trough concentrations correlate well with AUC, making therapeutic drug monitoring practical for dose optimization 6

• No hepatic dose adjustment is required even in severe hepatic dysfunction 1

• Fluconazole clearance is highly variable in critically ill patients and strongly dependent on actual renal function, not just baseline estimates 6