Santi Laurini Greta, Nikitina Victoria, Montanaro Nicola, Motola Domenico
Unit of Pharmacology, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
Pharmacology at the Alma Mater Studiorum University di Bologna, Bologna, Italy.
Fundam Clin Pharmacol. 2025 Aug;39(4):e70036. doi: 10.1111/fcp.70036.
Despite limited paediatric approvals, the use of proton pump inhibitors (PPIs) among children has increased in recent years, and concerns have arisen about their safety, including the risk of allergies. To provide additional evidence on the paediatric safety of PPIs, we performed a study on suspected adverse drug reactions (ADRs) in clinical practice.
We retrieved from EudraVigilance reports of suspected ADRs for PPIs in the age class 0-11 years in the period 2003-2022. Most reported ADRs and allergic conditions were evaluated by descriptive analysis. A case-non-case analysis was performed using reporting odds ratio (ROR) with a 95% confidence interval (CI). Chi-square or Fisher's exact tests were used to detect differences in reporting rates.
A total of 1389 reports and 4157 suspected ADRs were analysed. Most reports involved omeprazole (46.9%) and esomeprazole (27.3%), and 75.8% concerned serious outcomes. Gastrointestinal disorders were among the most common suspected ADRs, with vomiting being the most frequently reported (2.3%). Among allergic conditions, there were six cases of toxic epidermal necrolysis, five of Stevens-Johnson syndrome and four of drug reaction with eosinophilia and systemic symptoms. Statistically significant reactions for omeprazole were choking (ROR 5.54; 95% CI, 1.04-29.56) and pneumonia (3.61; 1.41-9.20), while for esomeprazole gastrointestinal disorder (7.57; 1.18-48.60) and constipation (4.74; 2.25-9.98).
Most common suspected ADRs reported with paediatric PPI use in Europe were gastrointestinal disorders, consistent with the safety profile in the product license. However, a high proportion of serious ADRs and few cases of severe cutaneous adverse reactions were reported.
尽管儿科用药批准有限，但近年来质子泵抑制剂（PPI）在儿童中的使用有所增加，人们对其安全性产生了担忧，包括过敏风险。为了提供更多关于PPI儿科安全性的证据，我们开展了一项关于临床实践中疑似药物不良反应（ADR）的研究。
我们从EudraVigilance中检索了2003年至2022年期间0至11岁年龄组中PPI的疑似ADR报告。大多数报告的ADR和过敏情况通过描述性分析进行评估。使用报告比值比（ROR）和95%置信区间（CI）进行病例-非病例分析。采用卡方检验或费舍尔精确检验来检测报告率的差异。
共分析了1389份报告和4157例疑似ADR。大多数报告涉及奥美拉唑（46.9%）和埃索美拉唑（27.3%），75.8%涉及严重后果。胃肠道疾病是最常见的疑似ADR之一，呕吐是报告最多的（2.3%）。在过敏情况中，有6例中毒性表皮坏死松解症、5例史蒂文斯-约翰逊综合征和4例伴有嗜酸性粒细胞增多和全身症状的药物反应。奥美拉唑具有统计学意义的反应是窒息（ROR 5.54；95% CI，1.04 - 29.56）和肺炎（3.61；1.41 - 9.20），而埃索美拉唑的是胃肠道疾病（7.57；1.18 - 48.60）和便秘（4.74；2.25 - 9.98）。
欧洲报告的儿童使用PPI最常见的疑似ADR是胃肠道疾病，与产品许可证中的安全性概况一致。然而，报告的严重ADR比例较高，严重皮肤不良反应病例较少。
