Itraconazole and Voriconazole: The Complexity of Dose Adjustments

To the Editor—Hendrix and colleagues showed that voriconazole in histoplasmosis was associated with increased mortality in the first 42 days compared with itraconazole [1]. This study seems significant because it exhibited the efficacy of voriconazole in histoplasmosis when itraconazole is recommended for histoplasmosis therapy [2]. However, we raise 2 issues in this study: antifungal dose adjustments and drug interactions. Serum drug concentration monitoring is recommended for both itraconazole and voriconazole. In particular, the voriconazole dose should be adjusted based on serum voriconazole concentrations. However, this study did not provide the dose and serum concentration of both antifungals. Thus, whether the dose was appropriately adjusted was unclear. Furthermore, it is crucial to consider drug interactions when discussing azoles. Approximately 60% of patients included in this study were immunocompromised. Thus, some of these patients could have been using drugs that interact with azoles. Both itraconazole and voriconazole...