Fluconazole (Diflucan) Treatment Regimens
Candidemia and Invasive Candidiasis in Adults
For most adult patients with candidemia, fluconazole should be administered as a loading dose of 800 mg (12 mg/kg), followed by 400 mg (6 mg/kg) daily, and is recommended for patients who are less critically ill and have had no recent azole exposure. 1
Initial Therapy Selection
- Fluconazole is appropriate for non-critically ill patients without recent azole exposure 1
- For moderately severe to severe illness or recent azole exposure, echinocandins are preferred over fluconazole 1
- Transition from an echinocandin to fluconazole is recommended once the patient is clinically stable and the isolate is confirmed susceptible (e.g., Candida albicans) 1
Species-Specific Considerations
- For C. glabrata infections, echinocandins are preferred; do not transition to fluconazole without documented susceptibility testing 1
- For C. parapsilosis infections, fluconazole is the preferred agent 1
- For C. krusei, use voriconazole as this species has intrinsic fluconazole resistance 1
Duration and Adjunctive Measures
- Continue therapy for 2 weeks after documented clearance of Candida from bloodstream and resolution of symptoms 1
- Central venous catheter removal is strongly recommended in non-neutropenic patients 1
Vulvovaginal Candidiasis
A single oral dose of fluconazole 150 mg is highly effective for uncomplicated vulvovaginal candidiasis, achieving clinical cure rates of 69% and therapeutic cure rates of 55%. 2
Treatment Approach
- Single 150 mg oral dose for uncomplicated cases 3, 2
- This regimen is comparable to 7-day topical azole therapy 2, 4
- Clinical cure or improvement occurs in 94-97% of patients by day 14 4
Recurrent Vulvovaginal Candidiasis
- For recurrent disease (≥4 episodes per year), fluconazole 150 mg weekly for 6 months is recommended after initial control 1
- Patients with recurrent vaginitis have lower cure rates (57% clinical, 40% therapeutic) compared to acute cases 2
Important Caveats
- Approximately 23% of patients experience relapse, reinfection, or recolonization at long-term follow-up 5
- Treatment of sexual partners is not recommended as vulvovaginal candidiasis is not sexually transmitted 3
Oropharyngeal and Esophageal Candidiasis
For oropharyngeal candidiasis, fluconazole 100 mg daily for a minimum of 14 days achieves a 90.4% clinical cure rate. 6
Dosing Regimens
- Oropharyngeal candidiasis: 100 mg daily for at least 14 days 6
- Esophageal candidiasis: 100 mg daily for at least 3 weeks 6
- In pediatric immunocompromised patients, 2-3 mg/kg/day achieves 86% clinical cure versus 46% with nystatin 2
Relapse Considerations
- Relapse rates are high (40%) in immunocompromised patients regardless of antifungal used 6, 7
- Long-term prophylaxis may be necessary in chronically immunocompromised patients, particularly those with AIDS 7
Urinary Tract Candidiasis
For symptomatic cystitis, fluconazole 200 mg (3 mg/kg) daily for 2 weeks is recommended. 1
Clinical Scenarios
- Asymptomatic candiduria typically does not require treatment unless the patient is high-risk (neonates, neutropenic adults) or undergoing urologic procedures 1
- For pyelonephritis: fluconazole 200-400 mg (3-6 mg/kg) daily for 2 weeks 1
- For urologic procedures in high-risk patients: fluconazole 200-400 mg (3-6 mg/kg) daily for several days before and after the procedure 1, 8
Alternative Therapy
- For fluconazole-resistant organisms (C. krusei, C. glabrata), use amphotericin B deoxycholate 0.3-0.6 mg/kg daily 1
Central Nervous System Candidiasis
For CNS candidiasis, lipid formulation amphotericin B 3-5 mg/kg daily with or without flucytosine 25 mg/kg four times daily is the preferred initial therapy, with fluconazole 400-800 mg (6-12 mg/kg) daily reserved for step-down therapy. 1
Treatment Protocol
- Initial therapy: Lipid formulation amphotericin B ± flucytosine 1
- Step-down therapy after clinical response: fluconazole 12 mg/kg daily for susceptible isolates 1
- Continue therapy until all signs, symptoms, CSF abnormalities, and radiological findings have resolved 1
- Remove infected CNS devices (ventriculostomy drains, shunts) whenever possible 1
Neonatal Candidiasis
For neonatal disseminated candidiasis, amphotericin B deoxycholate 1 mg/kg IV daily is the first-line agent, with fluconazole 12 mg/kg IV or oral daily as a reasonable alternative in patients not on fluconazole prophylaxis. 1
Neonatal Dosing
- Amphotericin B deoxycholate: 1 mg/kg daily (preferred) 1
- Fluconazole: 12 mg/kg daily (alternative if no prior fluconazole prophylaxis) 1
- Duration: 2 weeks after clearance of Candida from bloodstream and resolution of symptoms 1
Essential Adjunctive Measures
- Perform lumbar puncture and dilated retinal examination in all neonates with positive blood/urine cultures 1
- Remove central venous catheters 1
Cardiac Device and Endocarditis
For native valve endocarditis, lipid formulation amphotericin B 3-5 mg/kg daily ± flucytosine OR high-dose echinocandin is recommended for initial therapy, with step-down to fluconazole 400-800 mg (6-12 mg/kg) daily for susceptible isolates in stable patients. 1
Treatment Strategy
- Initial therapy: Lipid formulation amphotericin B or high-dose echinocandin 1
- Step-down therapy: fluconazole 400-800 mg (6-12 mg/kg) daily for susceptible organisms after clinical stability 1
- Valve replacement is strongly recommended 1
- For prosthetic devices that cannot be removed, chronic suppression with fluconazole 400-800 mg (6-12 mg/kg) daily is recommended 1, 8
Prophylaxis in High-Risk Settings
In neonatal intensive care units with invasive candidiasis rates >10%, fluconazole prophylaxis 3-6 mg/kg twice weekly is recommended. 1
Prophylactic Indications
- High-risk nurseries: fluconazole 3-6 mg/kg twice weekly 1
- Urologic procedures (e.g., penile prosthesis): fluconazole 400 mg (6 mg/kg) daily for several days before and after the procedure 8
Pharmacokinetic Considerations
Fluconazole exhibits excellent bioavailability (>93%), linear dose-concentration relationships, and penetrates well into body fluids including CSF, with an elimination half-life of approximately 30-37 hours allowing once-daily dosing. 6, 9
Key Pharmacokinetic Properties
- Bioavailability exceeds 93% for oral formulations 6
- Peak plasma concentrations occur at 2.4-3.7 hours 6
- Volume of distribution: 46.3 ± 7.9 L 6
- Elimination half-life: 30-37 hours 6, 9
- Approximately 60% excreted unchanged in urine within 48 hours 6
- Dose adjustment required in renal impairment 8
- Food intake, hypochlorhydria, and gastrointestinal resection do not affect absorption 6