Itraconazole for prophylaxis of systemic mycoses in neutropenic patients with haematological malignancies.

The efficacy of oral itraconazole 2 x 200 mg capsules daily for prevention of systemic mycoses was investigated in granulocytopenic patients with haematological malignancies. Of 241 patients, 197 were evaluable for prophylactic efficacy, and 214 for adverse events. Patients with similar characteristics receiving oral amphotericin B as antifungal prophylaxis, observed over 15 months before introduction of itraconazole, served as control group (n = 223). With itraconazole prophylaxis, 13 cases of aspergillosis (9 proven, 1 probable, 3 possible; 7%) and no systemic yeast infection occurred, compared with 14 episodes of aspergillosis (9 proven, 2 probable, 3 possible; 6%) and 3 proven systemic yeast infections (Candida albicans, Candida norvegensis, Trichosporon beigelii) in the historical group. Adverse events were observed in 13% of evaluable patients receiving itraconazole. In four patients with acute lymphoblastic leukaemia receiving itraconazole and vincristine simultaneously, severe vinca alkaloid-induced neurotoxicity occurred. Plasma concentrations of itraconazole and hydroxyitraconazole were measured in 64 patients. After eight days of itraconazole the median drug concentration was adequate (700 ng/mL), but there was a marked individual variation (229-2861 ng/mL). In comparison with a historical group, antifungal prophylaxis with itraconazole reduced the incidence of systemic yeast infections, but the frequency of aspergillosis was similar. However, a general increasing incidence of aspergillus infections at our hospital over the last four years should be considered in the assessment of study results.