Fluconazole (Diflucan) Treatment and Dosing for Fungal Infections
Fluconazole dosing varies significantly by infection type and severity, with vaginal candidiasis requiring only a single 150 mg dose, while life-threatening systemic infections demand 400-800 mg daily with loading doses. 1, 2
Vaginal Candidiasis
- A single oral dose of 150 mg is the standard treatment for uncomplicated vaginal candidiasis 2
- This achieves 88-97% cure rates at long-term follow-up 3
- For recurrent vulvovaginal candidiasis, use 150 mg weekly for 6 months after initial control 1
Oropharyngeal Candidiasis
- Topical agents are preferred first-line for mild disease 4, 5
- For moderate to severe cases: 200 mg loading dose on day 1, then 100 mg once daily for 7-14 days 2, 4
- In pediatric patients: 6 mg/kg on day 1, then 3 mg/kg once daily for at least 2 weeks 2
- Relapse rates approach 40% in immunocompromised patients regardless of antifungal used 6
Esophageal Candidiasis
- Standard dosing: 200 mg on day 1, then 100 mg once daily for 14-21 days minimum 2, 4
- Doses up to 400 mg daily may be used based on clinical response in severe cases 2, 4
- Treatment should continue for at least 2 weeks following symptom resolution 2
Candidemia and Invasive Candidiasis
Initial Therapy Selection
- For moderately severe to severe illness or recent azole exposure, echinocandins are preferred over fluconazole 1
- Fluconazole is appropriate for less critically ill patients without recent azole exposure 1
- Loading dose: 800 mg (12 mg/kg) on day 1, then 400 mg (6 mg/kg) daily 1
Species-Specific Considerations
- For C. albicans: Fluconazole is effective and preferred for step-down therapy 1
- For C. glabrata: Echinocandins are preferred; fluconazole should not be used without susceptibility confirmation 1
- For C. parapsilosis: Fluconazole is preferred over echinocandins 1
- For C. krusei: Fluconazole has no activity; use alternative agents 5
Duration and Catheter Management
- Continue therapy for 2 weeks after documented clearance from bloodstream and symptom resolution 1
- Intravenous catheter removal is strongly recommended in non-neutropenic patients 1
- All patients should undergo ophthalmological examination 1
Urinary Tract Infections
Asymptomatic Candiduria
- Treatment is NOT recommended unless patient is high-risk (neutropenic, very low birth weight <1500g, or undergoing urologic procedures) 1
- Elimination of indwelling bladder catheters is strongly recommended 1
Symptomatic Cystitis
- For fluconazole-susceptible organisms: 200 mg (3 mg/kg) daily for 2 weeks 1, 4
- For fluconazole-resistant C. glabrata: Amphotericin B deoxycholate 0.3-0.6 mg/kg daily for 1-7 days OR flucytosine 25 mg/kg four times daily for 7-10 days 1
- For C. krusei: Amphotericin B deoxycholate 0.3-0.6 mg/kg daily for 1-7 days 1
Pyelonephritis
- For fluconazole-susceptible organisms: 200-400 mg (3-6 mg/kg) daily for 2 weeks 1, 4
- Elimination of urinary tract obstruction is strongly recommended 1
- Consider removal or replacement of nephrostomy tubes or stents if present 1
Central Nervous System Infections
Cryptococcal Meningitis
- Initial therapy: Liposomal amphotericin B 5 mg/kg daily with or without flucytosine 25 mg/kg four times daily 1
- Step-down therapy: Fluconazole 400-800 mg (6-12 mg/kg) daily after patient responds 1
- Treatment duration: 10-12 weeks after CSF becomes culture negative 2
- Maintenance therapy for AIDS patients: 200 mg once daily to prevent relapse 2
Device Management
- Infected CNS devices (ventriculostomy drains, shunts, stimulators) should be removed if possible 1
Pediatric Dosing Equivalents
- 3 mg/kg in children ≈ 100 mg in adults 4
- 6 mg/kg in children ≈ 200 mg in adults 4
- 12 mg/kg in children ≈ 400 mg in adults (doses exceeding 600 mg/day not recommended) 2
Neonatal Considerations
- Premature newborns (26-29 weeks gestation): Use same mg/kg dose as older children but administer every 72 hours for first 2 weeks of life 2
- After 2 weeks: Dose once daily 2
Critical Resistance Patterns and Pitfalls
- Fluconazole has NO activity against C. krusei and variable activity against C. glabrata 5
- Resistance can develop, particularly in patients with recurrent or chronic infections 4
- Candida isolated from respiratory secretions usually represents colonization, not infection, and rarely requires treatment 4, 5
- Do not use azoles in neutropenic patients with prior azole prophylaxis 1
Pharmacokinetic Advantages
- Bioavailability exceeds 93% for oral formulations; daily dose is identical for oral and IV administration 2, 6
- Excellent penetration into CSF, vaginal secretions, saliva, and other body fluids at concentrations comparable to blood 6
- Long half-life (31-37 hours) allows once-daily dosing 6
- Loading doses of twice the daily dose are recommended on day 1 to achieve steady-state concentrations by day 2 2