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.