Vanderbilt University School of Medicine, Nashville, TN, USA.
Office of Pediatric Therapeutics, Office of the Commissioner, Food and Drug Administration, 10903 New Hampshire Avenue, Building 32, Room 5158, Silver Spring, MD, 20993, USA.
Paediatr Drugs. 2019 Feb;21(1):47-58. doi: 10.1007/s40272-018-0318-9.
Half of prescription drugs commonly given to children lack product labeling on pediatric safety, efficacy, and dosing. Two drugs most widely used off-label in pediatrics are azithromycin and fentanyl. We sought to determine the risk of serious adverse events (SAEs) when oral azithromycin or intravenous/intramuscular fentanyl are used off-label compared to on-label in pediatric intensive care units (ICUs).
Six pediatric hospitals participated in a retrospective chart review of patients administered oral azithromycin (n = 241) or intravenous/intramuscular fentanyl (n = 367) between January 5, 2013 and December 26, 2014. Outcomes were SAEs by drug and labeling status: off-label compared to on-label by Food and Drug Administration (FDA)-approved age and/or indication. Statistical analysis was performed using logistic regression to estimate odds ratios (ORs) and Cox regression to estimate hazard ratios (HRs).
Twenty-one (9%) children receiving azithromycin experienced SAEs. Off-label use of azithromycin was not associated with a higher risk of SAE (OR 0.87, 95% CI 0.27-2.71, p = 0.81). Ninety-five (26%) children receiving fentanyl experienced SAEs. Fentanyl off-label use by both age and indication was not associated with a higher risk of overall SAEs compared to on-label use (OR 1.99, 95% CI 0.94-4.19, p = 0.07). However, the risk of the SAE respiratory depression was significantly greater when fentanyl was used off-label by both age and indication (OR 5.05, 95% CI 1.08-23.56, p = 0.044). Results based on HRs were similar.
Azithromycin off-label use in pediatric ICUs does not appear to be associated with an increased risk of SAEs. Off-label use of fentanyl appears to be more frequently associated with respiratory depression when used off-label by both age and indication in pediatric ICUs. Prospective studies should be undertaken to assess the safety and efficacy of fentanyl in the pediatric population so that data can be added to the FDA labeling.
常用的儿童处方药中，有一半缺乏关于儿科安全性、疗效和剂量的产品标签。在儿科中最广泛的两种超说明书使用的药物是阿奇霉素和芬太尼。我们旨在确定在儿科重症监护病房（PICU）中，与标签内用药相比，口服阿奇霉素或静脉/肌肉内芬太尼的超说明书使用的严重不良事件（SAE）风险。
六家儿童医院参与了一项回顾性病历审查，评估了 2013 年 1 月 5 日至 2014 年 12 月 26 日期间接受口服阿奇霉素（n=241）或静脉/肌肉内芬太尼（n=367）治疗的患者。药物和标签状态的结局为 SAE：根据食品和药物管理局（FDA）批准的年龄和/或适应证进行超说明书与标签内用药比较。使用逻辑回归估计比值比（OR）和 Cox 回归估计风险比（HR）进行统计分析。
21 名（9%）接受阿奇霉素治疗的患儿发生 SAE。阿奇霉素的超说明书使用与 SAE 风险增加无关（OR 0.87，95%CI 0.27-2.71，p=0.81）。95 名（26%）接受芬太尼治疗的患儿发生 SAE。与标签内用药相比，芬太尼的年龄和适应证双超说明书使用与总体 SAE 风险增加无关（OR 1.99，95%CI 0.94-4.19，p=0.07）。然而，当芬太尼的年龄和适应证双超说明书使用时，呼吸抑制的 SAE 风险显著增加（OR 5.05，95%CI 1.08-23.56，p=0.044）。基于 HR 的结果相似。
儿科 ICU 中阿奇霉素的超说明书使用似乎不会增加 SAE 的风险。在儿科 ICU 中，当芬太尼的年龄和适应证双超说明书使用时，与标签内用药相比，更常与呼吸抑制相关。应进行前瞻性研究，以评估芬太尼在儿科人群中的安全性和疗效，以便为 FDA 标签添加数据。
