Fluconazole Dosing Guidelines
Standard Dosing by Indication
For invasive candidiasis and candidemia, administer a loading dose of 800 mg (12 mg/kg) on day 1, followed by 400 mg (6 mg/kg) daily, continuing for 2 weeks after documented blood culture clearance and clinical improvement. 1, 2
Candida Infections
- Oropharyngeal candidiasis: Give 200 mg loading dose on day 1, then 100 mg once daily for at least 14 days 1, 2
- Esophageal candidiasis: Administer 200–400 mg loading dose on day 1, then 100–200 mg daily for minimum 3 weeks and at least 2 weeks after symptom resolution 3, 1
- Uncomplicated vaginal candidiasis: Single 150 mg oral dose achieves >90% clinical cure rates 2
- Recurrent vulvovaginal candidiasis: Use 150 mg weekly for 6 months as maintenance after initial control 2
- Candida cystitis (fluconazole-susceptible species): Treat with 200 mg daily for 2 weeks 1
- Candida pyelonephritis: Administer 200–400 mg daily for 2 weeks 1
- Asymptomatic candiduria: No treatment required in immunocompetent patients; for high-risk patients undergoing urologic procedures, give 200–400 mg daily for several days before and after 1, 2
Cryptococcal Infections
- Non-HIV cryptococcal meningitis: After 2-week amphotericin B induction, give 400 mg daily for 8–10 weeks (consolidation), then 200 mg daily for 6–12 months (maintenance) 1
- Transplant-recipient cryptococcal meningitis: Consolidation with 400–800 mg daily for 8 weeks, followed by 200–400 mg daily for 6–12 months 1
Coccidioidal Infections
- Coccidioidal meningitis: Administer 400–1200 mg daily; doses <400 mg are ineffective in adults without substantial renal impairment; lifelong therapy is required 1, 4
- Extrapulmonary soft-tissue coccidioidomycosis: Use 400 mg daily 1
- Bone or joint coccidioidomycosis: Fluconazole is preferred for at least 1–2 years 1
- Transplant recipients with coccidioidomycosis: Give 400 mg daily if clinically stable and renal function is normal 1
Renal Dose Adjustments
The critical threshold for fluconazole dose reduction is creatinine clearance (CrCl) ≤50 mL/min, NOT 60 mL/min—this is a common dosing error. 1, 4
Dosing Algorithm by Renal Function
- CrCl >50 mL/min: No dose modification required; use standard dosing for the indication 1, 4
- CrCl ≤50 mL/min (non-dialysis):
- Hemodialysis patients:
Pharmacokinetic Rationale
90% of fluconazole is excreted unchanged in urine; renal clearance falls proportionally with decreasing CrCl, leading to drug accumulation if not adjusted 1, 4
- Elimination half-life is ~30 hours in normal renal function and is markedly prolonged in renal impairment 1, 4, 5
- Urine concentrations reach 10–20 times serum levels, making fluconazole particularly suitable for urinary tract candidiasis even in renal impairment 4
Hepatic Impairment
- No dose adjustment is required in hepatic dysfunction 1
- However, monitor liver enzymes closely because fluconazole can cause hepatotoxicity, especially during prolonged therapy 1
Critical Drug Interactions
Fluconazole inhibits CYP3A4 and CYP2C9, necessitating careful review of all concomitant medications. 1, 4
- Warfarin: Reduce warfarin dose by ~50% and monitor INR closely 1
- Cyclosporine/Tacrolimus: Significant dose reductions required; therapeutic drug monitoring is essential 1
- Phenytoin: Monitor for increased anticonvulsant levels and toxicity 1
- Oral hypoglycemics: Monitor blood glucose closely 1
- Antiretroviral agents: Conduct careful evaluation for potential interactions 1
Special Populations
Transplant Recipients
- Use the same fluconazole dosing as non-transplant patients for most infections 1
- Close monitoring for interactions with immunosuppressants is mandatory 1
- When adjusting immunosuppression in transplant patients on fluconazole, reduce corticosteroids first before other agents 1
- Fluconazole clearance may be further reduced due to concurrent calcineurin inhibitors affecting renal function 4
Neutropenic Patients
- Manage as invasive candidiasis with 400–800 mg daily 1
Monitoring Recommendations
- Renal function: Check regularly; adjust dose promptly if CrCl falls ≤50 mL/min 1, 4
- Hepatic function: Monitor for signs of hepatotoxicity, especially during prolonged therapy 1
- Fluconazole serum levels: Routine therapeutic drug monitoring is NOT required 1
- If flucytosine is co-administered: Measure flucytosine concentrations (target 40–60 µg/mL), particularly in renal impairment 1
Critical Pitfalls to Avoid
- Do NOT reduce fluconazole dose at CrCl 60 mL/min; the correct threshold is ≤50 mL/min 1, 4
- Always give the full loading dose on day 1, even in renal impairment; only the maintenance dose is reduced thereafter 1, 4
- Fluconazole is NOT appropriate for CNS aspergillosis; voriconazole should be used instead 1
- For coccidioidal meningitis, never use <400 mg daily in adults without substantial renal impairment 1, 4
- Avoid fluconazole for suspected C. glabrata or C. krusei infections, as these species have reduced susceptibility; consider echinocandins instead 2
- Do not use fluconazole prophylaxis in immunocompetent patients taking antibiotics, as it promotes resistance without proven benefit 2
- If azole prophylaxis was used, do not use azoles for empiric therapy; switch to an echinocandin 2
Key Pharmacokinetic Advantages
- Oral bioavailability exceeds 90%, permitting seamless IV-to-oral transition 1, 2
- Once-daily dosing is suitable because of the ~30-hour half-life 1, 4
- Absorption is not affected by food, gastric pH, or disease state 2
- CSF concentrations reach 50–89% of serum levels, making it ideal for CNS infections 2
- Fluconazole can persist in tissues for up to 6 months after discontinuation 1, 4