a Pediatric Hematology Oncology , Azienda Ospedaliera Universitaria Integrata , Verona , Italy.
Expert Rev Anti Infect Ther. 2018 Jul;16(7):543-553. doi: 10.1080/14787210.2018.1490177. Epub 2018 Jul 3.
Posaconazole is a broad-spectrum triazole widely used to prevent and treat invasive mycoses in adults. Since it received marketing authorization more than a decade ago, many authors have reported on its off-label use in pediatric patients, despite the fact that the pharmacokinetics, safety, and efficacy in children have not been extensively investigated. Areas covered: We reviewed pediatric studies published between 2010 and 2017 describing the prophylactic and therapeutic use of posaconazole, with special attention to the correlation between oral dose, plasma levels, safety, and effectiveness. We found that posaconazole is well tolerated in children with a low incidence of adverse effects. As in adults, posaconazole absorption is hampered by factors such as high gastric pH, mucositis, and concomitant medications, whereas there is no direct correlation between the daily dose and the trough plasma concentration due to saturable absorption. Expert Commentary: Posaconazole has proved safe and effective in preventing and treating fungal infections in immunocompromised children. A body-weight-based dosing regimen and therapeutic drug monitoring are recommended to optimize posaconazole plasma concentration. Absorption can be improved by high-fat foods or avoiding the use of proton-pump inhibitors. Further pediatric studies are needed especially for the new formulations of posaconazole (vials and tablets).
泊沙康唑是一种广谱三唑类药物,广泛用于预防和治疗成人侵袭性真菌感染。自十多年前获得上市许可以来,尽管儿童的药代动力学、安全性和疗效尚未得到广泛研究,但许多作者已报告其在儿科患者中的超适应证使用。
我们回顾了 2010 年至 2017 年期间发表的描述泊沙康唑预防性和治疗性使用的儿科研究,特别关注口服剂量、血浆水平、安全性和疗效之间的相关性。我们发现泊沙康唑在儿童中耐受性良好,不良反应发生率低。与成人一样,泊沙康唑的吸收受到高胃 pH 值、黏膜炎和同时使用的药物等因素的影响,而由于吸收达到饱和,每日剂量与谷浓度之间没有直接相关性。
泊沙康唑已被证明在预防和治疗免疫功能低下儿童的真菌感染方面是安全有效的。推荐基于体重的给药方案和治疗药物监测,以优化泊沙康唑的血浆浓度。高脂肪食物或避免使用质子泵抑制剂可改善吸收。需要进一步开展儿科研究,特别是针对泊沙康唑的新剂型(小瓶和片剂)。