Clinical Safety of Long-Term Intravenous Itraconazole for the Treatment of Invasive Fungal Infection In Severely Ill Patients with Hematological Malignancies

Abstract 4943

The clinical safety of intravenous itraconazole use exceeding 14 days is unknown. However, many cases need further treatment, but the absorption of itraconazole oral in severely ill patients is variable and unpredictable. Gastric acidity and food influence the absorption of oral formulation. The intravenous formulation, on the other hand, achieves adequate blood levels more rapidly and its bioavailability is predictable and invariable compared to the oral formulation. We performed this study to investigate the clinical safety of long-term intravenous itraconazole for the treatment of invasive fungal infection (IFI) in severely ill patients with hematological malignancies. 20 patients (median age, 70 years; range, 38–82 years) with hematological malignancies who had met the IFI inclusion criteria were enrolled. All the infection sites were the lung. These patients were given intravenous itraconazole for 14 days. There were significant effective but the lesions were not fully absorbed and no severe adverse events were found. So the long-term intravenous itraconazole therapy was enabled. Clinical efficacy and adverse events were recorded. Itraconazole 200 mg via intravenous infusion (administered over 1 hour) twice a day for 4 doses followed by 200 mg once a day until the lesions was fully absorbed. The treatment median time was 27(18-58) days. During this period, closely monitor changes in vital signs, chest CT, liver enzymes, renal function, electrocardiogram and electrolytes were assessed. We found that the patients achieved composite endpoints including survival, defervescence and undetectable lesions, except one patient died of primary disease - acute myeloid leukemia. Treatment-related adverse events were found in 7 patients (35%) during the study and none of them were severe adverse events. Such as hypokalemia (10.0%), gastrointestinal disorders (10.0%), elevation of liver enzymes (10.0%) and pleural effusion (5.0%). All the adverse events occurred during the first two weeks of the treatment and no significant exacerbation in the following days.

In conclusion, long-term intravenous itraconazole therapy was effective for IFI and the drug-related adverse events have been shown to be generally predictable and manageable.