Fluconazole Dose Reduction in Renal Impairment
Reduce the fluconazole dose to half when the creatinine clearance (CrCl) is less than 50 mL/min. 1, 2
Dosing Algorithm Based on Renal Function
For CrCl >50 mL/min
- No dose adjustment required - administer standard dosing (50-400 mg daily depending on indication) 1, 3, 2
For CrCl ≤50 mL/min (not on dialysis)
- Administer a full loading dose (50-400 mg based on indication) on Day 1 2
- Reduce maintenance dose to 50% of the standard dose starting Day 2 1, 2
- Example: If standard dose is 400 mg daily, give 400 mg loading dose, then 200 mg daily maintenance 3
For Patients on Hemodialysis
- Administer 100% of the recommended dose after each hemodialysis session 1, 2
- On non-dialysis days, patients should receive the reduced dose according to their creatinine clearance 2
- Approximately 50% of fluconazole is removed during a 3-hour hemodialysis session 4
Critical Threshold Clarification
The threshold of CrCl <50 mL/min is the established cutoff, not 60 mL/min as sometimes mistakenly cited 3. This is based on the pharmacokinetic principle that fluconazole is cleared primarily by renal excretion as unchanged drug, with approximately 80% appearing in urine 2. The elimination half-life increases significantly with declining renal function - approximately three times longer in patients with CrCl <20 mL/min compared to normal volunteers 4.
Important Clinical Considerations
Pharmacokinetic Rationale
- Fluconazole renal clearance correlates directly with GFR 4
- The elimination half-life in normal volunteers is approximately 30 hours (range 20-50 hours), but extends to 73.6 hours in premature newborns and increases proportionally with declining renal function 2, 4
- Non-renal clearance also decreases with worsening renal function, compounding the need for dose adjustment 4
Common Pitfalls to Avoid
- Do not use the 60 mL/min threshold - this is incorrect and may lead to unnecessary dose reductions 3
- Always administer the full loading dose regardless of renal function to achieve therapeutic concentrations rapidly 2
- Monitor for drug interactions - fluconazole inhibits CYP3A4 regardless of renal dosing adjustments 3
Special Populations
- Elderly patients may have reduced creatinine clearance characteristic of aging, requiring dose adjustment based on calculated CrCl rather than age alone 2, 5
- Critically ill patients on continuous renal replacement therapy may require higher doses due to enhanced drug clearance through dialysis circuits 6