Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
Sci Rep. 2024 Apr 20;14(1):9074. doi: 10.1038/s41598-024-59710-3.
Serious hematological adverse drug reactions (HADRs) may lead to or prolong hospitalization and even cause death. The aim of this study was to determine the regulatory factors associated with HADRs caused by drugs that were authorized up to July 2023 by the European Medicines Agency (EMA) and to evaluate the frequency of HADRs. Using a cross-sectional approach, the type and frequency of HADRs were collected from the Summaries of Product Characteristics of Drugs Authorized by the EMA and analyzed within proprietary, nonproprietary, and biosimilar/biological frameworks. Multivariate statistical analysis was used to investigate the associations of generic status, biosimilar status, conditional approval, exceptional circumstances, accelerated assessment, orphan drug status, years on the market, administration route, and inclusion on the Essential Medicines List (EML) with HADRs. In total, 54.78% of proprietary drugs were associated with HADRs at any frequency, while anemia, leucopenia, and thrombocytopenia were observed in approximately 36% of the patients. The predictors of any HADR, anemia, and thrombocytopenia of any frequency are generic status, biosimilar status, and inclusion on the EML, while the only protective factor is the administration route. Biosimilars and their originator biologicals have similar frequencies of HADRs; the only exception is somatropin. Knowledge of the regulatory factors associated with HADRs could help clinicians address monitoring issues when new drugs are introduced for the treatment of patients.
严重的药物不良反应（HADR）可能导致或延长住院时间，甚至导致死亡。本研究旨在确定与截至 2023 年 7 月由欧洲药品管理局（EMA）批准的药物相关的 HADR 监管因素，并评估 HADR 的频率。采用横断面研究方法，从 EMA 批准药物的产品特性概要中收集 HADR 的类型和频率，并在专有、非专有和生物类似物/生物制品框架内进行分析。采用多变量统计分析方法研究通用状态、生物类似物状态、有条件批准、特殊情况、加速评估、孤儿药状态、上市时间、给药途径和列入基本药物清单（EML）与 HADR 之间的关联。专有药物中，约有 54.78%的药物在任何频率下都与 HADR 相关，而贫血、白细胞减少和血小板减少在约 36%的患者中出现。任何 HADR、贫血和任何频率的血小板减少的预测因子是通用状态、生物类似物状态和列入 EML，而唯一的保护因素是给药途径。生物类似物及其原始生物制品的 HADR 频率相似，唯一的例外是生长激素。了解与 HADR 相关的监管因素可以帮助临床医生在为治疗患者而引入新药时解决监测问题。
