Clinical application of voriconazole concentrations in the treatment of invasive aspergillosis

Abstract

Objective: To review the current literature to determine the clinical application of therapeutic drug monitoring of voriconazole in the treatment of invasive aspergillosis (IA).

Data source: A MEDLINE search (1966-June 2008) was performed using the search terms voriconazole, aspergillosis, levels, monitoring, and serum concentration.

Study selection and data extraction: All pertinent English-language literature on voriconazole use in adults was included for evaluation.

Data synthesis: IA is a serious fungal infection with a mortality rate of nearly 100% without adequate treatment; current therapeutic options are limited. A clinical trial comparing amphotericin B deoxycholate with voriconazole in treatment of IA found voriconazole to be superior. The use of voriconazole, however, is complicated due to its saturable metabolism, nonlinear kinetic profile, and drug interactions, which result in considerable interpatient variability in concentrations. Therefore, therapeutic monitoring of voriconazole trough concentrations may lead to improved patient outcomes. A recent prospective study on the use of voriconazole for treatment of invasive mycoses demonstrated that 46% of the patients had a lack of response when trough plasma concentrations were less than or equal to 1 microg/mL, compared with 12% of patients with trough concentrations greater than 1 microg/mL (p = 0.02). All patients with low trough concentrations who did not respond to voriconazole improved upon dose escalation. The upper limit of a therapeutic range is based on the presence of adverse events. The most common adverse effects associated with voriconazole are visual disturbances (21%) and elevations in liver transaminase levels (12.4%). Current literature suggests that a greater incidence of adverse effects may be associated with trough concentrations greater than 6 microg/mL.

Conclusions: A standardized therapeutic range for voriconazole has not been defined. Most available studies recommend trough concentrations of approximately 1-6 microg/mL. Prospective, randomized trials are needed to confirm the correlation between plasma voriconazole concentrations and clinical outcomes.