What is the recommended dose of fluconazole (an antifungal medication) for an adult patient with normal renal function and impaired renal function, respectively?

Fluconazole Dosing Recommendations

Standard Dosing for Adults with Normal Renal Function

For invasive candidiasis and candidemia, initiate fluconazole with an 800 mg (12 mg/kg) loading dose on day 1, followed by 400 mg (6 mg/kg) daily. 1, 2

Dosing by Infection Type

Oropharyngeal Candidiasis:

• Mild disease: 100-200 mg daily for 7-14 days 1
• Moderate to severe disease: 100-200 mg daily for 7-14 days 1

Esophageal Candidiasis:

• 200-400 mg (3-6 mg/kg) daily for 14-21 days 1
• Continue until clinical improvement is documented 1

Urinary Tract Infections:

• Symptomatic cystitis: 200 mg (3 mg/kg) daily for 14 days 1, 3
• Pyelonephritis: 200-400 mg (3-6 mg/kg) daily for 14 days 1
• Critical caveat: Do NOT treat asymptomatic candiduria in immunocompetent patients 4

Candidemia/Invasive Candidiasis:

• Loading dose: 800 mg (12 mg/kg) on day 1 1, 2
• Maintenance: 400 mg (6 mg/kg) daily 1, 2
• Duration: Continue for 2 weeks AFTER first negative blood culture AND resolution of symptoms, not from start of therapy 1, 4

Cryptococcal Infections:

• Consolidation therapy: 400-600 mg daily for 8 weeks 1
• Maintenance therapy: 200 mg (3 mg/kg) daily for 6-12 months 1
• Non-meningeal cryptococcosis (mild-moderate): 400 mg daily for 6-12 months 1

Vulvovaginal Candidiasis:

• Uncomplicated: Single dose of 150 mg orally achieves >90% cure rate 4
• Recurrent (≥4 episodes/year): 150 mg weekly for 6 months 4

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Dosing Adjustments for Impaired Renal Function

For patients with creatinine clearance ≤50 mL/min (not on dialysis), reduce the maintenance dose to 50% of the standard dose after administering the full loading dose. 1, 2, 5

Specific Renal Dosing Algorithm:

Step 1: Administer full loading dose (50-400 mg depending on indication) 5

Step 2: Adjust maintenance dose based on creatinine clearance:

• CrCl >50 mL/min: 100% of standard dose 5
• CrCl ≤50 mL/min (no dialysis): 50% of standard dose 1, 2, 5

Step 3: For hemodialysis patients:

• Administer 100% of the recommended dose after EACH hemodialysis session 1, 2, 5
• For serious infections: 400 mg post-HD, 3 times weekly 2
• On non-dialysis days: Give reduced dose according to creatinine clearance 5

Hemodialysis-Specific Regimen:

Loading dose: 800 mg (12 mg/kg) on day 1, followed by 400 mg (6 mg/kg) after each hemodialysis session (3 times weekly for standard intermittent HD). 2

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Critical Pitfalls to Avoid

Species-Specific Resistance:

• C. krusei is intrinsically fluconazole-resistant; use amphotericin B or echinocandins instead 4
• C. glabrata may develop resistance during therapy; if fluconazole-resistant, switch to amphotericin B deoxycholate 0.3-0.6 mg/kg daily 1, 4

Duration Errors:

• Do NOT discontinue therapy based solely on symptom resolution 4
• For candidemia, duration is 2 weeks AFTER first negative blood culture, not from treatment initiation 1, 4

Inappropriate Prophylaxis:

• Do NOT use fluconazole prophylaxis routinely in immunocompetent patients on antibiotics—this promotes resistance without proven benefit 4

Pregnancy:

• Fluconazole is contraindicated in pregnancy 4

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Special Populations

Neonates and Infants:

• Recommended daily dosage: 6 mg/kg 6
• First 2 weeks of life: Administer every 72 hours 5, 6
• Weeks 2-4 of life: Administer every 48 hours 6
• After 4 weeks: Daily dosing appropriate 6
• For disseminated candidiasis in neonates: 12 mg/kg IV or oral daily 1

Critically Ill ICU Patients:

• Recent evidence suggests higher clearance than expected 7
• Recommended doses: 400 mg for poor-moderate renal function, 600 mg for adequate renal function, 800 mg for patients on CRRT 7
• Trough concentrations correlate well with AUC, enabling therapeutic drug monitoring 7

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Pharmacokinetic Considerations

Key Properties:

• Bioavailability exceeds 93% for tablets, suspension, and suppositories 8
• Low protein binding (11-23%) 8
• Long half-life: 31-37 hours in patients 8
• Primarily eliminated unchanged in urine (60% in 48 hours) 8
• No adjustment needed for hepatic dysfunction 2
• Food intake does not affect absorption 8

Therapeutic Drug Monitoring:

• Target plasma concentrations: 4-20 mcg/mL 6
• For invasive infections, target fAUC/MIC ratio of 100 (EUCAST recommendation) 7