Fluconazole (Diflucan) Adult Dosing
Fluconazole dosing in adults varies by indication, with a loading dose of 800 mg (12 mg/kg) followed by 400 mg (6 mg/kg) daily for invasive candidiasis, while uncomplicated vaginal candidiasis requires only a single 150 mg dose. 1, 2
Dosing by Clinical Indication
Invasive Candidiasis/Candidemia
- Loading dose: 800 mg (12 mg/kg) on day 1, then 400 mg (6 mg/kg) daily 1, 3
- Continue for 2 weeks after documented clearance of Candida from bloodstream and resolution of symptoms 1, 3
- Fluconazole is recommended for less critically ill patients without recent azole exposure 1
- For moderately severe to severe illness or recent azole exposure, echinocandins are preferred over fluconazole 1
Oropharyngeal Candidiasis
- 200 mg loading dose on day 1, then 100 mg daily 3, 2
- Treat for at least 2 weeks to decrease relapse likelihood 2
- Clinical resolution typically occurs within several days 2
Esophageal Candidiasis
- 200 mg on day 1, then 100 mg daily 2
- Doses up to 400 mg daily may be used based on clinical response 2
- Treat for minimum 3 weeks and at least 2 weeks after symptom resolution 2
Vaginal Candidiasis
- Single dose of 150 mg orally 3, 2
- Clinical cure rates exceed 90% 3, 4
- For recurrent vulvovaginal candidiasis: 150 mg weekly for 6 months as maintenance therapy 3
Urinary Tract Infections
- Asymptomatic candiduria in immunocompetent patients requires no treatment 3
- Symptomatic cystitis: 200 mg daily for 2 weeks 3
- Pyelonephritis: 200-400 mg daily for 2 weeks 3
- For general Candida UTI and peritonitis: 50-200 mg daily 2
Cryptococcal Meningitis
- Acute treatment: 400 mg on day 1, then 200 mg daily 2
- Up to 400 mg daily may be used based on response 2
- Treat for 10-12 weeks after CSF becomes culture negative 2
- Suppression therapy in AIDS patients: 200 mg daily 2
Prophylaxis in High-Risk Patients
- Bone marrow transplant: 400 mg daily starting several days before anticipated neutropenia, continuing for 7 days after neutrophil count >1000 cells/mm³ 2
- Solid organ transplant (liver, pancreas, small bowel): 200-400 mg (3-6 mg/kg) daily for 7-14 days postoperatively 1
- ICU patients at high risk: 400 mg (6 mg/kg) daily 1
- Chemotherapy-induced neutropenia: 400 mg (6 mg/kg) daily during neutropenia 1
Critical Dosing Adjustments
Renal Impairment
- For creatinine clearance ≤50 mL/min: reduce dose to 50% of recommended dose 3, 2
- Hemodialysis patients: give 100% of recommended dose after each dialysis session 3
Loading Dose Principle
- A loading dose of twice the daily dose is recommended on day 1 to achieve near steady-state concentrations by day 2 2
- This applies to all indications except single-dose vaginal candidiasis 2
Important Pharmacokinetic Considerations
Bioavailability and Administration
- Oral bioavailability is approximately 90%, making oral and IV dosing equivalent 3, 5
- Absorption is not affected by food, gastric pH, or disease state 3, 5
- Peak concentrations (Cmax) occur at 2.4-3.7 hours 5
Tissue Penetration
- CSF concentrations reach 50-89% of serum levels, making fluconazole ideal for CNS infections 3, 5
- Urine concentrations reach 10-20 times serum levels 3
- Excellent penetration into vaginal secretions, breast milk, saliva, and sputum 5
Elimination
- Half-life: 22-37 hours, allowing once-daily dosing 5, 6
- Primarily eliminated unchanged in urine (approximately 60% in 48 hours) 5
- Low protein binding (11-23%) 5
Critical Pitfalls to Avoid
Species-Specific Considerations
- Avoid fluconazole for suspected C. glabrata or C. krusei infections due to reduced susceptibility; use echinocandins instead 1, 3
- For C. parapsilosis, fluconazole is preferred over echinocandins 1
- Do not transition from echinocandin to fluconazole without confirming species susceptibility 1
Prophylaxis Misuse
- Do not use fluconazole prophylaxis in immunocompetent patients taking antibiotics, as it promotes resistance without proven benefit 3
- Azole prophylaxis precludes empiric azole therapy; prior azole exposure necessitates switching to echinocandins for empiric treatment 1, 3
Treatment Duration Errors
- Inadequate treatment duration leads to recurrence of active infection 2
- Always continue therapy until clinical parameters or laboratory tests indicate fungal infection has subsided 2
- AIDS patients with cryptococcal meningitis or recurrent oropharyngeal candidiasis require maintenance therapy to prevent relapse 2