What is the appropriate fluconazole (antifungal medication) dose for a patient with impaired renal function (creatinine level 1.33)?

From the Guidelines

For a patient with impaired renal function (creatinine level 1.33), the fluconazole dose should be adjusted to approximately 50-75% of the standard dose, depending on the indication, as recommended by the most recent guidelines 1.

Key Considerations

• The patient's creatinine level of 1.33 indicates moderate renal impairment, which affects the body's ability to clear fluconazole, a medication primarily eliminated by the kidneys 1.
• According to the guidelines for preventing opportunistic infections among HIV-infected persons, for patients with renal dysfunction and a creatinine clearance of <50 mL/min, the fluconazole dose should be reduced to half of the standard dose 1.
• For most indications, if the standard dose would be 400 mg daily, consider reducing to 200-300 mg daily, and for less severe infections typically treated with 200 mg daily, a reduction to 100-150 mg daily would be appropriate.

Monitoring and Adjustments

• Regular monitoring of renal function during treatment is recommended to further adjust dosing if needed, as renal impairment can lead to drug accumulation and toxicity if standard doses are used 1.
• It's also important to monitor for side effects such as nausea, headache, abdominal pain, and liver function abnormalities, which may be more pronounced in patients with renal impairment.

Special Considerations

• For patients on hemodialysis, a full dose should be administered after each dialysis session, as recommended by the guidelines 1.
• The selection of appropriate patients for empiric antifungal therapy should be based on clinical risk factors, serologic tests, and culture data, and the duration of therapy should be individualized based on the patient's response to treatment 1.

From the FDA Drug Label

Dosage In Patients With Impaired Renal Function: Fluconazole is cleared primarily by renal excretion as unchanged drug. ... When serum creatinine is the only measure of renal function available, the following formula (based on sex, weight, and age of the patient) should be used to estimate the creatinine clearance in adults: Males: Weight (kg) x (140 - age) ————————————— 72 x serum creatinine (mg/100 mL) Females: 0. 85 × above value Although the pharmacokinetics of fluconazole has not been studied in children with renal insufficiency, dosage reduction in children with renal insufficiency should parallel that recommended for adults.

Creatinine Clearance (mL/min) Recommended Dose (%)

50 100 ≤50 (no dialysis) 50 Hemodialysis 100% after each hemodialysis

To determine the appropriate dose, we need to estimate the creatinine clearance. Given the serum creatinine level is 1.33, we can use the formula for adults:

• For males: Weight (kg) x (140 - age) / (72 x serum creatinine (mg/100 mL))
• For females: 0.85 × above value

However, without the patient's weight, age, and sex, we cannot calculate the creatinine clearance directly.

Assuming we had this information, if the creatinine clearance is:

• >50 mL/min, the recommended dose is 100%.
• ≤50 mL/min (no dialysis), the recommended dose is 50%.
• For patients on hemodialysis, the dose should be 100% after each hemodialysis, and on non-dialysis days, the dose should be adjusted according to the creatinine clearance.

Since we lack specific patient details (weight, age, sex) necessary for calculating creatinine clearance and thus determining the exact dosage adjustment for a creatinine level of 1.33, a precise dose cannot be recommended. It's crucial to consult with a healthcare provider to assess the patient's overall condition and calculate the appropriate dose based on individual factors 2.

From the Research

Fluconazole Dosing in Renal Impairment

The appropriate fluconazole dose for a patient with impaired renal function, specifically a creatinine level of 1.33, can be determined by considering the patient's creatinine clearance (CrCl).

• The CrCl can be estimated using the Cockcroft-Gault equation, which takes into account the patient's age, weight, sex, and serum creatinine level 3.
• Studies have shown that fluconazole's pharmacokinetics are affected by impaired renal function, with a significant increase in the area under the plasma concentration-time curve (AUC) and terminal elimination half-life (t1/2) in patients with moderate to severe renal impairment 4, 3.
• The dose adjustment for fluconazole in patients with renal impairment is typically based on the CrCl, with a recommended dose reduction of 50% for patients with a CrCl of 50 mL/min or less 3.
• However, it is essential to note that the estimated glomerular filtration rate (eGFR) may not accurately predict aspects of proximal tubule drug handling, and dose modification should be individualized based on the patient's specific renal function and other factors 5.

Key Considerations

• The patient's CrCl should be estimated using the Cockcroft-Gault equation to determine the appropriate fluconazole dose.
• Fluconazole's pharmacokinetics are significantly affected by impaired renal function, and dose adjustment is necessary to avoid toxicity.
• The recommended dose reduction for fluconazole in patients with renal impairment is 50% for those with a CrCl of 50 mL/min or less.
• Individualized dose modification is crucial, considering the patient's specific renal function and other factors, as eGFR may not accurately predict proximal tubule drug handling.

Relevant Studies

• 4 An assessment of the effects of impaired renal function and haemodialysis on the pharmacokinetics of fluconazole.
• 3 The effects of renal impairment on the pharmacokinetics and safety of fosfluconazole and fluconazole following a single intravenous bolus injection of fosfluconazole.
• 5 GFR may not accurately predict aspects of proximal tubule drug handling.