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.