Review of Serum Voriconazole Concentrations and Correlations with Adverse Events and Efficacy

Abstract

Objective: To review the available evidence regarding the monitoring of serum voriconazole concentrations in terms of efficacy and safety. Data Sources: A literature search of MEDLINE was conducted (1950–February 2009), with combinations of the following search terms: voriconazole, therapeutic drug monitoring, voriconazole serum concentrations, voriconazole levels, trough, and adverse events. Data Collection: All studies and case reports that evaluated serum voriconazole concentrations in adults were reviewed and considered for inclusion. Citations in identified articles were searched for additional information. Data Synthesis: Ten studies and case reports that evaluated serum voriconazole concentrations in terms of efficacy and safety in adults were identified and included in this review. Results from efficacy studies show an association between low serum voriconazole concentrations and disease progression. One study found that a lack of response occurred more often in patients with a serum voriconazole trough of 1 μg/mL or less (p = 0.02). Another study found that patients were more likely to fail voriconazole therapy for invasive fungal infections when serum concentrations were less than or equal to 2 μg/mL. In terms of safety, 6 studies showed an association between elevated serum voriconazole concentrations and adverse events. Conclusions: Available data suggest that serum voriconazole concentrations of 1 μg/mL or less are associated with therapeutic failures, whereas serum voriconazole concentrations of 6 μg/mL or more are associated with adverse events. Studies show that monitoring serum voriconazole concentrations may decrease the incidence of adverse events while increasing efficacy.