泊沙康唑
加药
医学
不利影响
治疗药物监测
移植
内科学
造血干细胞移植
科克伦图书馆
药理学
胃肠病学
荟萃分析
药代动力学
抗真菌
皮肤病科
伊曲康唑
作者
Heather Weerdenburg,Hannah Walker,Nigel Curtis,Stephen B. Duffull,Gabrielle M Haeusler,Theresa Cole,Amanda Gwee
摘要
Abstract Objectives Posaconazole is increasingly used for the treatment and prophylaxis of invasive fungal infections in immunocompromised children. We aimed to review evidence for paediatric posaconazole dosing regimens focusing on attainment of target concentrations and frequency of adverse effects. Methods In May 2023, the Cochrane, Embase, MEDLINE and PubMed databases were searched for articles reporting posaconazole dosing in children with malignancy or post-haematopoietic stem cell transplantation. Studies reporting the attainment of target serum concentrations were included. Results Overall, 24 studies were included. Eighteen studies of the oral suspension consistently reported poor attainment of target concentrations for prophylaxis (≥0.7 µg/mL, 12%–78%) despite high daily doses of 14–23 mg/kg/day (max. 1200 mg/day). Target attainment was significantly affected by gastric pH and food intake. Six studies of the delayed-release tablet (DRT) reported 58%–94% achieved concentrations ≥0.7 µg/mL, with the majority using lower doses of 4–12 mg/kg/day (max. 300 mg/day). Similarly, one study of powder for oral suspension found 67%–100% achieved target concentrations with a dose of 6 mg/kg/day (max. 300 mg/day). As expected, the IV formulation had high attainment of prophylaxis targets (81%–90%) with 6–10 mg/kg/day (max. 400 mg/day). All formulations were well tolerated, and no relationship between adverse effects and posaconazole concentrations was identified. Conclusions The required posaconazole dose in immunocompromised children varies depending on the formulation. The IV infusion had the highest attainment of therapeutic concentration followed by the DRT and powder for suspension. By contrast, the oral suspension had low attainment of target concentrations despite higher daily doses.
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