Fluconazole Dose Adjustment in CKD on Dialysis
Yes, fluconazole requires dose adjustment for patients with chronic kidney disease on dialysis—specifically, patients on hemodialysis should receive 100% of the recommended dose after each dialysis session. 1
Dosing Algorithm for Dialysis Patients
Loading Dose
- Administer the full loading dose (50-400 mg depending on indication) regardless of renal function 1
- This loading dose is critical because fluconazole has a long half-life (31.6 hours in normal renal function, extending to approximately 3 times longer in severe renal impairment) 2, 3
Maintenance Dosing on Hemodialysis
- Give 100% of the standard recommended dose after each hemodialysis session 1
- On non-dialysis days, administer 50% of the standard dose based on the patient being functionally anuric 1
- For example, if treating cryptococcal meningitis (standard dose 400 mg daily), give 400 mg after each dialysis and 200 mg on non-dialysis days 4
Rationale for Post-Dialysis Dosing
Approximately 38% of a fluconazole dose is removed during a 3-hour hemodialysis session 3. This substantial dialytic clearance necessitates replacement dosing immediately following dialysis to maintain therapeutic levels 4.
Continuous Renal Replacement Therapy (CRRT)
If the patient is on CRRT instead of intermittent hemodialysis, the dosing differs significantly:
- CVVH (continuous veno-venous hemofiltration): Multiply the anuric dose by 2.2 (ultrafiltrate flow 0.5 L/h) 5
- CVVHD (continuous veno-venous hemodiafiltration): Multiply the anuric dose by 3.8 (combined dialysate/ultrafiltrate flow 1.5 L/h) 5
- Recent evidence suggests critically ill patients on CRRT may require 800 mg daily to achieve adequate exposure 6, 7
The higher clearance with CVVHD (30.5 ml/min) compared to CVVH (17.5 ml/min) explains why CVVHD requires substantially higher doses 7.
Indication-Specific Dosing Examples
Cryptococcal Meningitis
- Standard dose: 400-1200 mg daily 4
- Hemodialysis: 400-1200 mg after each dialysis session; 200-600 mg on non-dialysis days 4
Candidemia/Invasive Candidiasis
- Standard dose: 400-800 mg daily 4
- Hemodialysis: Full dose after dialysis; 50% dose on non-dialysis days 1
Oropharyngeal Candidiasis
Critical Monitoring Considerations
Therapeutic drug monitoring is strongly recommended for dialysis patients receiving fluconazole for life-threatening infections 5, 7. Trough concentrations correlate well with AUC and can guide dose adjustments 6.
Target Concentrations
- For invasive infections, target fAUC/MIC ratio of 100 6
- Trough levels of 1-3 mg/L are typical for prophylaxis; 20 mg/L may be needed for severe infections 2
Common Pitfalls to Avoid
- Do not reduce the loading dose in dialysis patients—the volume of distribution is unchanged 1, 2
- Do not assume all dialysis modalities are equivalent—CRRT removes significantly more fluconazole than intermittent hemodialysis 5, 7
- Do not forget post-dialysis supplementation—this is when drug levels are lowest 4, 1
- Do not use creatinine clearance formulas alone—they may underestimate clearance in dialysis patients; use the specific dialysis-based dosing recommendations 1