Does Voriconazole (Voriconazole) require dialysis in patients with Impaired renal function?

From the Guidelines

Voriconazole does not require dialysis in patients with impaired renal function, as it is primarily metabolized by the liver and has minimal renal clearance. When considering the management of patients with impaired renal function, it is crucial to understand the pharmacokinetics of voriconazole. According to the clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America 1, voriconazole's oral bioavailability is excellent and not affected by gastric pH, but it decreases when the drug is administered with food.

Key Points to Consider:

• The guideline states that intravenous voriconazole is complexed to a cyclodextrin molecule, and because of the potential for cyclodextrin accumulation and possible nephrotoxicity among patients with significant renal dysfunction, intravenous voriconazole is not currently recommended for patients with a creatinine clearance <50 mL/minute 1.
• However, oral voriconazole does not require dosage adjustment for renal insufficiency, as it is primarily metabolized by the liver and has minimal renal clearance 1.
• It is essential to note that voriconazole has a narrow therapeutic window, and close monitoring of voriconazole levels is recommended in patients with impaired renal function due to potential variability in drug metabolism.
• The standard dosing regimen for voriconazole should be used, with a loading dose of 400 mg (6 mg/kg) twice daily for 2 doses, followed by 200–300 mg (3–4 mg/kg) twice daily 1.

Important Considerations:

• Common polymorphisms in the gene encoding the primary metabolic enzyme for voriconazole result in wide variability of serum levels 1.
• Drug–drug interactions are common with voriconazole and should be considered when initiating and discontinuing treatment with this compound 1.
• Voriconazole has not been studied systematically in fluconazole-resistant Candida species, and with the exception of C. krusei, use is currently discouraged 1.

From the FDA Drug Label

In a single oral dose (200 mg) study in 24 subjects with normal renal function and mild to severe renal impairment, systemic exposure (AUC) and peak plasma concentration (C max) of voriconazole were not significantly affected by renal impairment. A pharmacokinetic study in subjects with renal failure undergoing hemodialysis showed that voriconazole is dialyzed with clearance of 121 mL/min A 4-hour hemodialysis session does not remove a sufficient amount of voriconazole to warrant dose adjustment

Voriconazole does not require dialysis in patients with impaired renal function, as a 4-hour hemodialysis session does not remove a sufficient amount of voriconazole to warrant dose adjustment 2.

From the Research

Voriconazole and Dialysis in Patients with Impaired Renal Function

• The need for dialysis in patients with impaired renal function taking Voriconazole is not explicitly stated in the provided studies, but some insights can be gathered from the pharmacokinetic properties of the drug.
• According to 3, Voriconazole penetrates well into peritoneal fluid, but there is minimal peritoneal clearance of the drug, suggesting that dialysis may not be necessary for removing Voriconazole from the body.
• However, 4 notes that the administration of Voriconazole by the intravenous route in patients with moderate or severe renal failure is limited due to potential toxic effects of the accumulation of the solvent vehicle sulphobutylether beta cyclodextrin sodium.
• The study 4 found that the use of intravenous Voriconazole in ICU patients with pretreatment impaired renal function was not associated with renal or liver damage, but it does not provide direct evidence on the need for dialysis.
• Another study 5 mentions that approximately 80% of the total dose of Voriconazole is recovered in the urine, almost completely as metabolites, which may imply that patients with impaired renal function could accumulate the drug or its metabolites, potentially requiring dose adjustment rather than dialysis.
• Overall, while there is no direct evidence to suggest that Voriconazole requires dialysis in patients with impaired renal function, caution is advised when administering the drug to such patients, and dose adjustment may be necessary to avoid potential toxic effects 6.