From the Guidelines
Fluconazole (Diflucan) dosing should be adjusted in patients with impaired renal function, with a recommended dose reduction of 50% for patients with creatinine clearance (CrCl) less than 50 mL/min, and full dose administered after each dialysis session for patients on hemodialysis. The adjustment is crucial because fluconazole is primarily eliminated unchanged through the kidneys, and reduced kidney function can lead to drug accumulation and increased side effects 1. For patients with CrCl greater than 50 mL/min, no adjustment is needed, and standard dosing can be used. However, for those with CrCl between 11-50 mL/min, administering 50% of the normal dose while maintaining the same dosing interval is recommended. Patients with severe renal impairment (CrCl ≤10 mL/min), including those on dialysis, should receive the reduced dose, with the full recommended daily dose given after each dialysis session. It's also important to note that fluconazole has a long half-life, which becomes significantly prolonged in renal impairment, necessitating monitoring for adverse effects such as elevated liver enzymes, nausea, headache, and rash, as well as checking for potential drug interactions since fluconazole is a moderate CYP3A4 inhibitor 1.
Key Considerations for Dosing Adjustments
- Creatinine clearance (CrCl) is the primary factor in determining the need for dosing adjustments
- Patients with CrCl < 50 mL/min require a 50% reduction in the standard dose
- Patients on hemodialysis should receive the full recommended daily dose after each dialysis session
- Monitoring for adverse effects and potential drug interactions is crucial in patients with renal impairment
Rationale for Adjustments
- Fluconazole is primarily eliminated unchanged through the kidneys
- Reduced kidney function leads to drug accumulation and potentially increased side effects
- The long half-life of fluconazole becomes significantly prolonged in renal impairment, increasing the risk of adverse effects 1
From the FDA Drug Label
Dosage In Patients With Impaired Renal Function: Fluconazole is cleared primarily by renal excretion as unchanged drug. There is no need to adjust single dose therapy for vaginal candidiasis because of impaired renal function. In patients with impaired renal function who will receive multiple doses of fluconazole tablets, an initial loading dose of 50 mg to 400 mg should be given After the loading dose, the daily dose (according to indication) should be based on the following table: Creatinine Clearance (mL/min) Recommended Dose (%)
50 100 ≤50 (no dialysis) 50 Hemodialysis 100% after each hemodialysis Patients on hemodialysis should receive 100% of the recommended dose after each hemodialysis; on non-dialysis days, patients should receive a reduced dose according to their creatinine clearance.
The dosing adjustments for Diflucan (fluconazole) in patients with impaired renal function are as follows:
- No adjustment is needed for single-dose therapy for vaginal candidiasis.
- For multiple-dose therapy, an initial loading dose of 50-400 mg should be given.
- The daily dose should be adjusted based on creatinine clearance:
- >50 mL/min: 100% of recommended dose
- ≤50 mL/min (no dialysis): 50% of recommended dose
- Hemodialysis: 100% of recommended dose after each hemodialysis, and a reduced dose on non-dialysis days according to creatinine clearance. 2
From the Research
Dosing Adjustments for Diflucan in Patients with Impaired Renal Function
The dosing adjustments for Diflucan (fluconazole) in patients with impaired renal function are as follows:
- For patients with creatinine clearance (CLcr) greater than 50 mL/min, no dose adjustment is necessary 3.
- For patients with CLcr between 21 and 50 mL/min, the maintenance dose should be reduced to 50% of the normal dose, with a loading dose of 200 mg and a maintenance dose of 100 mg/day 3.
- For patients with CLcr between 11 and 20 mL/min, the maintenance dose should be reduced to 25% of the normal dose, with a loading dose of 100 mg and a maintenance dose of 50 mg/day 3.
- For patients on hemodialysis, a loading dose of 200 mg should be administered after each dialysis session, with a maintenance dose of 100 mg after each dialysis session 3.
Pharmacokinetics of Fluconazole in Renal Failure
The pharmacokinetics of fluconazole in renal failure have been studied, and the results show that:
- The mean area under the curve (AUC) measurements are approximately proportional to the dose of fluconazole and independent of renal function 3.
- The mean renal clearance of fluconazole decreases as CLcr decreases, and the mean half-lives are inversely related to mean CLcr 3.
- The mean AUC on Day 10 is similar for patients with normal renal function and those with moderate renal insufficiency, despite a reduction in the maintenance dose by 50% 3.
Clinical Considerations
It is essential to consider the renal function of patients when dosing Diflucan, as renal impairment can affect the pharmacokinetics of the drug 3, 4, 5. Additionally, other antifungal agents, such as amphotericin B, can have nephrotoxic effects, and their use should be carefully considered in patients with renal impairment 6, 4, 7.