What is the recommended dose of fluconazole for a patient with severe impaired renal function (creatinine clearance (CrCl) 23 ml/min)?

Fluconazole Dosing for CrCl 23 mL/min

For a patient with CrCl 23 mL/min requiring fluconazole 400 mg daily, reduce the maintenance dose to 200 mg daily after administering a full 400 mg loading dose. 1, 2, 3

Dosing Algorithm

Step 1: Administer Loading Dose

• Give the full 400 mg loading dose on Day 1, regardless of renal function 3
• Loading doses do not require adjustment because single-dose therapy is unaffected by renal impairment 3

Step 2: Calculate Maintenance Dose

• For CrCl ≤50 mL/min (including your patient with CrCl 23): Reduce maintenance dose by 50% 1, 2, 3
• Your patient's maintenance dose: 400 mg × 50% = 200 mg daily 1, 2, 3

Step 3: Timing Considerations

• Administer maintenance dose starting on Day 2 3
• Continue daily dosing (no need for alternate-day dosing at this level of renal impairment) 3

Evidence-Based Rationale

The 50% dose reduction threshold occurs at CrCl <50 mL/min, not at 60 mL/min 1, 2. This is critical because:

• Fluconazole is cleared primarily by renal excretion as unchanged drug (approximately 80% renal elimination) 3, 4
• The elimination half-life increases approximately 3-fold when CrCl drops below 20 mL/min compared to normal renal function 5
• AUC increases 2.4-fold in moderate impairment (CrCl 30-50) and 3.6-fold in severe impairment (CrCl <30) 6

Special Considerations for Your Patient

Hemodialysis Status

• If your patient requires hemodialysis: Give 100% of the recommended dose (400 mg) after each dialysis session 3
• On non-dialysis days: Use the reduced 200 mg dose based on CrCl 3
• Approximately 38% of fluconazole is removed during a 3-hour hemodialysis session 5

Monitoring Requirements

• Renal function should be monitored periodically as fluconazole clearance correlates linearly with creatinine clearance 6
• If renal function worsens further (CrCl <15 mL/min), the same 50% dose reduction applies 3
• Trough concentrations correlate well with AUC and can guide therapeutic drug monitoring if available 7

Common Pitfalls to Avoid

• Do not reduce the loading dose - this is a frequent error that leads to delayed achievement of therapeutic levels 3
• Do not use the 60 mL/min threshold - the actual cutoff for dose adjustment is 50 mL/min 1, 2
• Do not assume non-renal clearance compensates - non-renal clearance actually decreases with worsening renal function 5
• Do not forget drug interactions - fluconazole inhibits CYP3A4 and may require adjustment of concomitant medications regardless of renal dosing 1