Institute for Medical Biometry, Informatics and Epidemiology, University Hospital of Bonn, Bonn, Germany.
Research Division, Federal Institute for Drugs and Medical Devices, Bonn, Germany.
BMC Pharmacol Toxicol. 2021 Oct 7;22(1):56. doi: 10.1186/s40360-021-00520-y.
Adverse drug reactions (ADRs) in the pediatric population may differ in types and frequencies compared to other populations. Respective studies analyzing ADR reports referring to children have already been performed for certain countries. However, differences in drug prescriptions, among others, complicate the transferability of the results from other countries to Germany or were rarely considered. Hence, the first aim of our study was to analyze the drugs and ADRs reported most frequently in ADR reports from Germany referring to children contained in the European ADR database (EudraVigilance). The second aim was to set the number of ADR reports in relation to the number of drug prescriptions. These were provided by the Research Institute for Ambulatory Health Care in Germany.
For patients aged 0-17 years 20,854 spontaneous ADR reports were received between 01/01/2000-28/2/2019. The drugs and ADRs reported most frequently were identified. Stratified analyses with regard to age, sex and drugs used "off-label" were performed. Reporting rates (number of ADR reports/number of drug prescriptions) were calculated.
Methylphenidate (5.5%), ibuprofen (2.3%), and palivizumab (2.0%) were most frequently reported as suspected. If related to the number of drug prescriptions, the ranking changed (palivizumab, methylphenidate, ibuprofen). Irrespective of the applied drugs, vomiting (5.4%), urticaria (4.6%) and dyspnea (4.2%) were the ADRs reported most frequently. For children aged 0-1 year, drugs for the treatment of nervous system disorders and foetal exposure during pregnancy were most commonly reported. In contrast, methylphenidate ranked first in children older than 6 years and referred 3.5 times more often to males compared to females. If age- and sex-specific exposure was considered, more ADR reports for methylphenidate referred to children 4-6 years and females 13-17 years. Drugs for the treatment of nervous system disorders ranked first among "off-label" ADR reports.
Our analysis underlines the importance of putting the number of ADR reports of a drug in context with its prescriptions. Additionally, differences in age- and sex-stratified analysis were observed which may be associated with age- and sex-specific diseases and, thus, drug exposure. The drugs most frequently included in "off-label" ADR reports differed from those most often used according to literature.
与其他人群相比，儿科人群中的药物不良反应（ADR）在类型和频率上可能有所不同。已经针对某些国家开展了各自分析儿童 ADR 报告的研究。然而，由于药物处方等方面的差异，使得其他国家的研究结果难以在德国应用或很少被考虑。因此，我们研究的首要目标是分析在欧洲 ADR 数据库（EudraVigilance）中包含的德国儿童 ADR 报告中最常报告的药物和 ADR。其次，我们旨在确定 ADR 报告数量与药物处方数量之间的关系。这些数据由德国门诊医疗保健研究所提供。
在 2000 年 1 月 1 日至 2019 年 2 月 28 日期间，我们共收到 0-17 岁患者的 20854 例自发 ADR 报告。确定了最常报告的药物和 ADR。并根据年龄、性别和“超说明书”使用的药物进行分层分析。计算了报告率（ADR 报告数/药物处方数）。
哌醋甲酯（5.5%）、布洛芬（2.3%）和帕利珠单抗（2.0%）最常被报告为疑似药物。如果与药物处方数量相关，排名则发生变化（帕利珠单抗、哌醋甲酯、布洛芬）。无论使用何种药物，呕吐（5.4%）、荨麻疹（4.6%）和呼吸困难（4.2%）是最常报告的 ADR。对于 0-1 岁的儿童，最常报告的是治疗神经系统疾病的药物和怀孕期间胎儿暴露的药物。相比之下，哌醋甲酯在 6 岁以上的儿童中排名第一，并且报告给男性的比例是女性的 3.5 倍。如果考虑年龄和性别特异性暴露，哌醋甲酯的 ADR 报告更多地指向 4-6 岁的儿童和 13-17 岁的女性。治疗神经系统疾病的药物在“超说明书”ADR 报告中排名第一。
我们的分析强调了将药物的 ADR 报告数量与药物处方数量相结合的重要性。此外，还观察到了年龄和性别分层分析的差异，这可能与年龄和性别特异性疾病以及因此的药物暴露有关。“超说明书”ADR 报告中最常包含的药物与文献中最常使用的药物不同。
