What is the recommended dosing of fluconazole (Fluconazole) for a patient with Impaired renal function on Hemodialysis (HD) with a Candida wound infection?

Fluconazole Dosing for Candida Wound Infection in Hemodialysis Patients

For hemodialysis patients with Candida wound infections, administer fluconazole 400 mg (6 mg/kg) after each hemodialysis session. 1, 2

Loading Dose Strategy

• Initiate therapy with an 800 mg (12 mg/kg) loading dose on Day 1, followed by the maintenance regimen. 3, 2
• The loading dose ensures rapid achievement of therapeutic concentrations, which is critical given the prolonged half-life (72-85 hours) in dialysis patients compared to 31 hours in those with normal renal function. 4, 5

Maintenance Dosing for Hemodialysis

• Administer 400 mg (6 mg/kg) after each hemodialysis session (typically 3 times weekly for standard intermittent HD). 1, 2
• On non-dialysis days, no additional dose is required as fluconazole has a prolonged half-life in renal failure. 2
• The FDA label explicitly states that hemodialysis patients should receive 100% of the recommended dose after each dialysis session, as hemodialysis removes significant amounts of fluconazole. 2

Treatment Duration

• Continue therapy for at least 2 weeks after clinical resolution of the wound infection. 3
• For more severe or deep tissue involvement, extend treatment duration based on clinical response and imaging if applicable. 3
• Premature discontinuation significantly increases relapse risk. 3

Critical Considerations for Wound Infections

• Ensure adequate source control: debridement of necrotic tissue and drainage of any collections is essential for treatment success. 3
• If the isolate is C. glabrata or C. krusei, fluconazole may not be appropriate—consider amphotericin B deoxycholate 0.3-0.6 mg/kg daily or an echinocandin instead. 1
• Obtain susceptibility testing to confirm fluconazole susceptibility, as resistance patterns vary. 3, 1

Pharmacokinetic Rationale

• Fluconazole is primarily eliminated unchanged by the kidneys (60% recovered in urine over 48 hours in patients with normal function). 6, 4
• In hemodialysis, the extracorporeal clearance necessitates post-dialysis dosing to maintain therapeutic levels. 2, 4
• The sieving coefficient during hemodialysis approaches 0.88-0.96, indicating efficient removal during dialysis sessions. 7
• Between dialysis sessions, the prolonged half-life (72-85 hours) maintains adequate drug concentrations. 5

Common Pitfalls to Avoid

• Do not dose fluconazole on non-dialysis days in standard intermittent hemodialysis—this leads to excessive accumulation and potential toxicity. 2
• Avoid underdosing: the 400 mg post-dialysis dose is necessary for serious infections; lower doses (200 mg) are only appropriate for less severe infections like candiduria. 1, 2
• Do not assume all Candida species are fluconazole-susceptible: C. krusei is intrinsically resistant and C. glabrata often has reduced susceptibility. 1
• Maximum daily doses should not exceed 1600 mg to avoid neurological toxicity, though this is rarely relevant in standard wound infection management. 6

Alternative for Continuous Renal Replacement Therapy

• If the patient is on continuous venovenous hemodialysis (CVVHD) or hemodiafiltration (CVVHDF) rather than intermittent HD, dosing differs significantly. 8, 7
• For CVVHD with dialysate/ultrafiltrate flow of 1.5-2 L/h: multiply the standard anuric dose by 3.8, resulting in approximately 800 mg daily. 8, 7
• Drug monitoring is strongly recommended in CRRT due to highly variable clearance rates. 8, 7