Current experience with itraconazole in neutropenic patients: A concise overview of pharmacological properties and use in prophylactic and empirical antifungal therapy

Abstract

Itraconazole is a triazole broad-spectrum antifungal agent that can be given as capsules, oral solution or intravenous solution. Bioavailability in neutropenic patients is different between capsules (c. 23%) and oral solution (c. 55%). A dose-response relationship has been established for the use of itraconazole in antifungal prophylaxis: HPLC-determined trough concentrations of itraconazole need to be above 500ng/mL for effective prevention of invasive Aspergillus infections. A meta-analysis of 13 randomised clinical trials and 3597 neutropenic patients with haematological malignancies has demonstrated a 53% reduction in the incidence of invasive Aspergillus infections with a sufficient dose of itraconazole. Two randomised clinical trials evaluated itraconazole for empirical antimycotic therapy in neutropenic patients with persisting fever despite broad-spectrum antibiotic therapy in comparison to conventional amphotericin B. Both demonstrated significantly reduced nephrotoxicity and at least comparable efficacy. In conclusion, itraconazole should be regarded as the standard for antifungal prophylaxis in high-risk patients and a valuable therapeutic option for empirical antifungal therapy in these patients. © 2006 European Society of Clinical Microbiology and Infectious Diseases.