Factors affecting voriconazole pharmacokinetic variability in critically ill patients: a systematic review.

BACKGROUND: The efficacy and toxicity of voriconazole, a broad-spectrum antifungal agent, are correlated with its trough concentration (Ctrough). Patients hospitalised in the intensive care unit (ICU) frequently experience inadequate voriconazole exposure. We sought to identify factors associated with variability of voriconazole Ctrough in ICU patients. METHODS: We searched MEDLINE, Web of Science and Cochrane Library databases from inception through July 2025. RESULTS: Thirty-one studies describing nine factors of variability were included. Liver dysfunction, high body mass index, high SOFA score and high inflammation status were associated with voriconazole overexposure, whereas the oral route of administration, renal replacement therapy and low body mass index were associated with voriconazole underexposure. The effects of extracorporeal membrane oxygenation and hypoalbuminemia on voriconazole exposure were unclear. CONCLUSIONS: A systematic dose adaptation is required for patients with liver dysfunction, and voriconazole dose calculation should not be based on total body weight, with an adjusted body weight a preferred alternative. Intravenous administration should be favoured in patients without severe renal dysfunction. Further research to define the benefit of an individualised dosing approach for voriconazole in ICU patients that combines pharmacokinetic modelling and machine learning, is warranted. Meanwhile, close therapeutic drug monitoring is needed for ICU patients, especially those with identified risk factors for under- or overexposure.