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Itraconazole for invasive fungal infection with pediatric malignancies
Ryoji Kobayashi1, Daisuke Suzuki, Kazue Yasuda
1Department of Pediatrics, Sapporo Hokuyu Hospital, Sapporo, Japan. r-koba@jacls.jp
Background:
Invasive fungal infection (IFI) is an increasingly common and often fatal infection in children with hematological malignancies and solid tumor. Prophylactic therapy with anti-fungal agents is very important for these patients, because the early diagnosis of IFI is very difficult.
Procedure:
A total of 0.5 mL/kg per day of itraconazole oral solution (ITCZ-OS) was administered in twice-daily doses to 22 children with hematological malignancies who had received chemotherapy, and its usefulness and safety regarding the prevention of IFI were examined.
Result:
Prophylactic therapy with ITCZ-OS was completed in 18 (81.8%) of the 22 children. Of these, IFI was not strongly suspected in any child. Side-effects included non-alcoholic steatohepatitis in two children, syndrome of inappropriate anti-diuretic hormone secretion in one, and liver dysfunction in one. The administration of ITCZ-OS was discontinued in these cases. These four children had received vincristine sulfate (VCR) or irinotecan hydrochloride, which were reported to interact with ITCZ. In most children the plasma levels of ITCZ were satisfactory. The plasma levels, however, were slightly increased in VCR-treated children; ITCZ should be carefully administered.
Conclusion:
Although the number of subjects was small in the present study, the plasma concentrations of ITCZ-OS favorably increased in the children with hematological malignancies, suggesting that this agent exhibits prophylactic effects on IFI. It must be considered, however, that some combined agents cause side-effects via their interactions with ITCZ.
Insights
Itraconazole oral solution (ITCZ-OS) shows promise in preventing invasive fungal infections (IFIs) in pediatric cancer patients. Careful administration is advised due to potential drug interactions and side effects.
Area of Science:
- Pediatric Oncology
- Infectious Diseases
- Pharmacology
Background:
- Invasive fungal infections (IFIs) pose a significant threat to children with hematological malignancies and solid tumors.
- Early diagnosis of IFIs in this vulnerable population is challenging, underscoring the importance of prophylactic antifungal therapy.
Purpose of the Study:
- To evaluate the efficacy and safety of itraconazole oral solution (ITCZ-OS) as a prophylactic agent against IFIs in children undergoing chemotherapy for hematological malignancies.
Main Methods:
- A total of 22 children with hematological malignancies received 0.5 mL/kg/day of ITCZ-OS in divided doses.
- The study monitored the prevention of IFIs, assessed side effects, and measured plasma levels of itraconazole.
Main Results:
- Prophylactic ITCZ-OS was completed by 81.8% of patients, with no suspected IFIs. Four children discontinued treatment due to side effects, including liver dysfunction and syndrome of inappropriate anti-diuretic hormone secretion, often associated with concomitant use of vincristine sulfate or irinotecan hydrochloride.
- Plasma levels of ITCZ were generally satisfactory, though slightly elevated in patients receiving vincristine sulfate, indicating a need for careful administration.
Conclusions:
- ITCZ-OS demonstrated favorable plasma concentrations and suggested prophylactic effects against IFIs in pediatric cancer patients.
- Potential drug interactions with agents like vincristine sulfate and irinotecan hydrochloride must be considered, as they may contribute to adverse events.
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