Itraconazole oral solution as antifungal prophylaxis in children undergoing stem cell transplantation or intensive chemotherapy for haematological disorders

Abstract

This was an open study of oral antifungal prophylaxis in 103 neutropenic children aged 0–14 (median 5) years. Most (90%) were undergoing transplantation for haematological conditions (77% allogeneic BMT, 7% autologous BMT, 6% PBSC transplants and 10% chemotherapy alone). They received 5.0 mg/kg itraconazole/day (in 10 mg/ml cyclodextrin solution). Where possible, prophylaxis was started at least 7 days before the onset of neutropenia and continued until neutrophil recovery. Of the 103 who entered the study, 47 completed the course of prophylaxis, 27 withdrew because of poor compliance, 19 because of adverse events and 10 for other reasons. Two patients died during the study and another five died within the subsequent 30 days. No proven systemic fungal infections occurred, but 26 patients received i.v. amphotericin for antibiotic-unresponsive pyrexia. One patient received amphotericin for mycologically confirmed oesophageal candidosis. Three patients developed suspected oral candidosis but none was mycologically proven and no treatment was given. Serious adverse events (other than death) occurred in 21 patients, including convulsions (7), suspected drug interactions (6), abdominal pain (4) and constipation (4). The most common adverse events considered definitely or possibly related to itraconazole were vomiting (12), abnormal liver function (5) and abdominal pain (3). Tolerability of study medication at end-point was rated as good (55%), moderate (11%), poor (17%) or unacceptable (17%). Some patients had poor oral intakes due to mucositis. No unexpected problems of safety or tolerability were encountered. We conclude that itraconazole oral solution may be used as antifungal prophylaxis for neutropenic children.