What is the recommended Voriconazole (Voriconazole) dose for a patient with impaired renal function (creatinine clearance of 25)?

Voriconazole Dosing in Renal Impairment (CrCl 25 mL/min)

Use oral voriconazole at standard doses (loading dose 400 mg twice daily for 2 doses, then 200-300 mg twice daily) without dose adjustment, as oral formulations do not require modification for renal impairment. 1, 2

Route Selection Based on Renal Function

Avoid intravenous voriconazole in patients with creatinine clearance <50 mL/min due to accumulation of the vehicle sulfobutylether-β-cyclodextrin (SBECD), which is renally cleared and may cause nephrotoxicity. 1, 2

Oral Formulation (Preferred Route)

• Standard loading dose: 400 mg (6 mg/kg) orally twice daily for 2 doses 1
• Maintenance dose: 200-300 mg (3-4 mg/kg) orally twice daily 1
• No dose adjustment required for any degree of renal impairment, including severe dysfunction 1, 2
• Oral bioavailability exceeds 90% and is not affected by gastric pH, though absorption decreases when administered with food 1

Intravenous Formulation (Use With Caution)

• Contraindicated per guidelines for CrCl <50 mL/min due to SBECD accumulation 1, 2
• If IV route is absolutely necessary and benefit outweighs risk, monitor serum creatinine closely and switch to oral therapy as soon as clinically feasible 1, 2

Evidence Regarding Safety in Renal Impairment

Guideline Recommendations

The IDSA guidelines explicitly state that intravenous voriconazole is not recommended for patients with creatinine clearance <50 mL/min, though retrospective data have not identified toxic effects in some patients with renal dysfunction below this threshold. 1

Clinical Evidence Supporting Cautious Use

Recent research provides nuanced perspective on IV voriconazole safety:

• A retrospective ICU study found that IV voriconazole in patients with impaired renal function (including serum creatinine >2.5 mg/dL) was not associated with increased renal or liver damage compared to those with normal renal function. 3

• A candidemia trial showed that IV voriconazole in patients with moderate (CrCl 30-50 mL/min) or severe (CrCl <30 mL/min) renal insufficiency resulted in less acute renal toxicity than amphotericin B/fluconazole (39% vs 53% worsening renal function). 4

• A prospective study of 166 patients found that voriconazole route of administration and baseline renal function were not predictors of worsening renal dysfunction; rather, underlying disease and concomitant medications were the strongest predictors. 5

Critical Pitfalls to Avoid

• Do not use IV voriconazole as first-line in patients with CrCl <50 mL/min when oral formulation is feasible, as the oral route provides equivalent systemic exposure without SBECD-related risks. 1, 2

• Do not adjust oral voriconazole doses based on renal function, as this may lead to subtherapeutic levels. 1, 2

• Monitor for hepatotoxicity regardless of route, as voriconazole requires dose reduction in hepatic impairment (reduce maintenance dose by 50% in Child-Pugh Class A or B). 1, 2

• Consider therapeutic drug monitoring due to wide interpatient variability from CYP2C19 polymorphisms, particularly in critically ill patients. 1

• Review drug interactions carefully as voriconazole is both substrate and inhibitor of CYP2C19, CYP2C9, and CYP3A4. 1

Hemodialysis Considerations

• Voriconazole is hemodialyzed (clearance 121 mL/min), but a 4-hour hemodialysis session does not remove sufficient drug to warrant dose adjustment. 2

• SBECD is also hemodialyzed (clearance 55 mL/min). 2

• No supplemental dosing is required post-dialysis. 2