What is the renal dose of fluconazole (injection fluconazole) for patients with systemic candidiasis and impaired renal function?

From the Guidelines

For patients with systemic candidiasis and impaired renal function, the renal dose of fluconazole should be adjusted based on creatinine clearance, with a loading dose of 800 mg (12 mg/kg) followed by a daily dose of 400 mg (6 mg/kg) for patients with creatinine clearance >50 mL/min, and a lower dosage required for patients with creatinine clearance <50 mL/min. When considering the management of systemic candidiasis in patients with impaired renal function, it is crucial to adjust the fluconazole dosage to prevent drug accumulation and potential toxicity 1. The adjustment of fluconazole dosing is based on creatinine clearance (CrCl), which is a key indicator of renal function.

Key Considerations

• For patients with CrCl >50 mL/min, the standard dose of 400 mg (6 mg/kg) IV on day 1, followed by 200-400 mg (3-6 mg/kg) IV daily, can be used.
• For patients with CrCl 11-50 mL/min, administering 50% of the recommended dose is necessary to avoid excessive drug levels.
• For patients with CrCl ≤10 mL/min, including those on hemodialysis, administering 25% of the recommended dose is required to minimize the risk of toxicity.
• Patients on hemodialysis should receive the full dose after each dialysis session to maintain adequate drug exposure.

Rationale

Fluconazole is primarily eliminated unchanged through the kidneys, and reduced renal function leads to drug accumulation and potential toxicity 1. Therefore, adjusting the dose based on creatinine clearance is essential to ensure effective treatment while minimizing adverse effects.

Additional Recommendations

Therapeutic drug monitoring may be beneficial in critically ill patients with renal dysfunction to ensure adequate drug exposure while minimizing adverse effects. Treatment duration for systemic candidiasis typically ranges from 14 days to several weeks, continuing for at least 14 days after the last positive blood culture and resolution of symptoms 1.

From the FDA Drug Label

In patients with impaired renal function who will receive multiple doses of fluconazole, an initial loading dose of 50 mg to 400 mg should be given After the loading dose, the daily dose (according to indication) should be based on the following table: Creatinine Clearance (mL/min) Recommended Dose (%)

50 100 ≤ 50 (no dialysis) 50 Hemodialysis 100% after each hemodialysis Patients on hemodialysis should receive 100% of the recommended dose after each hemodialysis; on non-dialysis days, patients should receive a reduced dose according to their creatinine clearance.

The renal dose of fluconazole for patients with systemic candidiasis and impaired renal function is as follows:

• Initial loading dose: 50 mg to 400 mg
• Daily dose:
  • Creatinine clearance > 50 mL/min: 100% of the recommended dose
  • Creatinine clearance ≤ 50 mL/min (no dialysis): 50% of the recommended dose
  • Hemodialysis: 100% of the recommended dose after each hemodialysis, and a reduced dose on non-dialysis days according to creatinine clearance 2

From the Research

Renal Dose of Fluconazole for Systemic Candidiasis

The renal dose of fluconazole for patients with systemic candidiasis and impaired renal function is as follows:

• For patients with poor to moderate renal function, a dose of 400 mg is recommended 3
• For patients with adequate renal function, a dose of 600 mg is recommended 3
• For patients treated with continuous renal replacement therapy (CRRT), a dose of 800 mg is recommended 3
• In patients with impaired renal function, the daily dose should be reduced in accordance with the guidelines given for adults 4
• Dosage reduction is advised for patients with impaired renal function 5

Key Considerations

• Fluconazole clearance is highly variable in ICU patients and is strongly dependent on renal function and CRRT 3
• The volume of distribution (Vd) of fluconazole remains stable at 46.3 +/- 7.9L and is considered to be an 'invariant' parameter across species 6
• Fluconazole is poorly metabolised and is mainly eliminated unchanged in the urine 6, 5
• The percentage of the dose recovered in the urine in 48 hours is close to 60% 6
• Concentrations in the urine are high and the half-life (t1/2) is long (37.2 +/- 5.5h) in patients, mainly those with AIDS 6

Special Populations

• In neonates during the first two weeks of life, the daily dosage should be administered only every 72 hours 4
• In weeks two to four of life, the same dose should be given every 48 hours 4
• After that daily dosing is appropriate 4