Research Division, Federal Institute for Drugs and Medical Devices, Bonn, Germany.
Institute for Medical Biometry, Informatics and Epidemiology, University Hospital of Bonn, Bonn, Germany.
Br J Clin Pharmacol. 2024 Mar;90(3):776-792. doi: 10.1111/bcp.15941. Epub 2023 Nov 28.
Adverse drug reactions (ADRs) are known to show sex-specific differences in occurrence and phenotype. The aim of this study was to analyse sex-specific differences in ADR-drug combinations that required hospitalization based on two different datasets.
We performed a complementary analysis of (i) spontaneously reported (n = 12 564, female = 51.7%) and (ii) systematically collected ADR reports from a prospective multicentre observational study (ADRED, n = 2355, female = 48.2%) from Germany in the ADR database EudraVigilance (EV). Both datasets were analysed separately concerning the suspected drugs, ADRs and ADR-drug combinations more frequently reported for females or males by calculating reporting odds ratios (ROR) with 95% confidence intervals. ADR-drug combinations more frequently reported for either females or males in EV reports were related to prescription data. Finally, the results from both datasets were discussed with regard to their (dis-)concordance.
In both datasets, some antineoplastic agents and nervous system drugs were found to be reported more often for females than males (RORs ranging from 1.5 [1.1-2.1] for quetiapine in spontaneous reports to 41.3 [13.1-130.0] for trastuzumab in spontaneous reports). ADRs of the respiratory system, and haemorrhages were described predominantly for males in both datasets. In spontaneous reports the ADR-drug combination self-injurious behaviour-quetiapine was more often reported for females without and with consideration of drug prescriptions (ROR: 3.8 [1.3-11.0]). Quetiapine and psychiatric disorders (superordinate level) was exclusively reported for females in ADRED reports.
Our results can contribute to raise awareness and further knowledge regarding sex-specific ADRs. The findings require further in-depth investigation.
已知药物不良反应（ADR）的发生和表型存在性别特异性差异。本研究旨在基于两个不同的数据集分析需要住院治疗的 ADR-药物组合的性别特异性差异。
我们对（i）自发报告（n=12564，女性=51.7%）和（ii）来自德国前瞻性多中心观察性研究（ADRED，n=2355，女性=48.2%）的系统收集的 ADR 报告进行补充分析，在 EudraVigilance（EV）ADR 数据库中。这两个数据集分别根据可疑药物、ADR 和 ADR-药物组合进行分析，通过计算报告比值比（ROR）及其 95%置信区间，确定女性或男性更常报告的 ADR-药物组合。在 EV 报告中，女性或男性更常报告的 ADR-药物组合与处方数据相关。最后，讨论了两个数据集的结果及其一致性。
在两个数据集均发现，一些抗肿瘤药和神经系统药物在女性中的报告频率高于男性（ROR 范围为 1.5[1.1-2.1]，如在自发报告中喹硫平，到 41.3[13.1-130.0]，如在自发报告中曲妥珠单抗）。两个数据集均发现，呼吸系统和出血性 ADR 主要发生在男性。在自发报告中，未考虑药物处方时，自伤行为-喹硫平的 ADR-药物组合更常报告给女性（ROR：3.8[1.3-11.0]）。在 ADRED 报告中，仅报告喹硫平和精神障碍（上位水平）给女性。
我们的研究结果可以有助于提高对性别特异性 ADR 的认识和进一步了解。这些发现需要进一步深入调查。
