What is the recommended dose of Diflucan (fluconazole) for a patient with impaired renal function, specifically a Glomerular Filtration Rate (GFR) of 29 and a creatinine level of 1.7?

Fluconazole Dosing for GFR 29 mL/min/1.73 m²

For a patient with GFR 29 mL/min/1.73 m² (Stage 4 CKD), give a loading dose of 50-400 mg based on indication, then reduce the maintenance dose by 50% of the standard daily dose. 1

Dosing Algorithm

Step 1: Determine Your Loading Dose

• Give the full loading dose appropriate for the infection type (50-400 mg depending on indication) 1
• The loading dose does NOT require adjustment for renal impairment 1

Step 2: Calculate Maintenance Dose

Since GFR 29 falls in the category of creatinine clearance ≤50 mL/min (no dialysis):

• Reduce the standard maintenance dose by 50% 1

Specific Examples by Indication:

• Oropharyngeal candidiasis: Loading dose 200 mg, then 100 mg daily (50% of standard 200 mg) 1
• Esophageal candidiasis: Loading dose 200 mg, then 100 mg daily (50% of standard 200 mg) 1
• Systemic candidiasis: Loading dose 400 mg, then 200 mg daily (50% of standard 400 mg) 1
• Cryptococcal meningitis: Loading dose 400 mg, then 200 mg daily (50% of standard 400 mg) 1

Pharmacokinetic Rationale

Why dose reduction is critical: Fluconazole is primarily eliminated unchanged by the kidneys, with renal clearance accounting for approximately 75% of total clearance 2. At GFR 29 mL/min/1.73 m², the elimination half-life extends from approximately 31 hours in normal renal function to 85-102 hours in severe renal impairment 3. Without dose adjustment, drug accumulation occurs rapidly, reaching potentially toxic levels 3.

The FDA labeling explicitly states that patients with creatinine clearance ≤50 mL/min who are not on dialysis should receive 50% of the recommended dose after the initial loading dose 1. This recommendation is supported by pharmacokinetic studies demonstrating that a 50% dose reduction maintains therapeutic AUC levels comparable to those in patients with normal renal function receiving standard doses 3.

Critical Monitoring Points

• Renal function: Monitor creatinine and eGFR at least twice yearly, or more frequently if clinical status changes 4
• Drug levels: Consider therapeutic drug monitoring if available, targeting trough concentrations of 1-3 mg/L for most infections 2
• Clinical response: Assess for treatment efficacy and adjust duration as needed based on infection resolution 1

Common Pitfalls to Avoid

• Do not skip the loading dose: The loading dose ensures rapid achievement of therapeutic levels and is safe even in severe renal impairment 1, 3
• Do not use standard maintenance doses: Failure to reduce the maintenance dose by 50% leads to drug accumulation and increased toxicity risk 5, 3
• Do not assume eGFR alone predicts drug handling: While fluconazole clearance correlates moderately with GFR (R² = 0.40-0.44), individual variation exists 6
• Do not forget this patient needs nephrology referral: At GFR 29 (Stage 4 CKD), immediate nephrology consultation is indicated to prepare for potential renal replacement therapy 4

Additional Renal Management Considerations

At GFR 29 mL/min/1.73 m², this patient requires comprehensive CKD management beyond fluconazole dosing:

• Discontinue metformin immediately if prescribed (contraindicated at eGFR <30) 4
• Reduce insulin doses by 35-50% due to decreased renal clearance 4
• Monitor for volume overload as fluid handling is severely impaired 4
• Screen for CKD complications: anemia, metabolic acidosis, secondary hyperparathyroidism 4