Intravenous Itraconazole followed by Oral Itraconazole for the Treatment of Amphotericin-B-Refractory Invasive Pulmonary Aspergillosis

The efficacy and safety of 2 weeks of intravenous itraconazole (200 mg twice daily for 2 days, then 200 mg once daily for 12 days) followed by 12 weeks of oral itraconazole capsules 200 mg twice daily were evaluated in a multicentre, open trial in 31 immunocompromised patients with invasive pulmonary aspergillosis (IPA). We report on a subset of 21 patients who had amphotericin-B-refractory IPA. All patients had haematological malignancies, 10 patients had failed prophylaxis, 12 patients had failed empirical therapy and 2 patients had failed treatment of confirmed infection with amphotericin B. By the second day of treatment, all patients assessed (n = 12) had trough plasma concentrations of itraconazole greater than 250 ng/ml. Mean trough plasma concentrations increased throughout the intravenous and oral treatment periods. Of the 10 patients who completed the 14 weeks of therapy, 9 (90%) had a complete or partial response and the remaining patient had stable disease. Overall, 11 of the 21 patients (52%) had a complete or partial response at their last assessment and three additional patients had stable disease. During intravenous treatment, 18 patients (86%) experienced adverse events; during oral treatment, 11 patients (52%) experienced adverse events. Most adverse events were not related to itraconazole treatment and all were expected in this patient population. In conclusion, intravenous itraconazole followed by oral itraconazole is an effective and well-tolerated treatment for amphotericin-B-refractory IPA. Copyright (C) 2003 S. Karger AG, Basel.