Hu Weiping, Li Hailong, Zeng Linan, Gan Jing, Feng Chenghong, Chen Li, Zhang Lingli
Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
BMC Pharmacol Toxicol. 2024 Dec 18;25(1):95. doi: 10.1186/s40360-024-00822-x.
H1-antihistamines are widely used to treat symptoms depending on histamine release in a variety of conditions. However, neurological adverse events have been reported in post-marketing surveillance studies and there are limited literatures comparing the neurological disorders associated with newer-generation H1-antihistamines from real-world datasets.
We performed a comparative analysis of nervous system disorders and several newer-generation H1-antihistamines including: cetirizine, loratadine, levocetirizine, desloratadine and fexofenadine.
Disproportionality analysis was used to identify the suspected drug neurological adverse events associated with H1-antihistamines of interest via the Food and Drug Administration Adverse Event Reporting System. The proportional reporting ratio (PRR), χ (chi-square) and the reporting odds ratio (ROR) with 95% confidence interval (CI) were used to estimate the association.
AE reports of 43,815 cases from 2017 to 2021 were extracted from FAERS. The H1-antihistamines included in our study were associated with various neurological adverse events that could be classified into 12 aspects, containing 42 preferred terms. The majority of adverse event reports were concentrated at somnolence: cetirizine [N = 1342, ROR (95%CI) = 11.8 (11.2-12.5), PRR = 10.8, χ = 11755.4], levocetirizine [N = 1276, ROR(95%CI) = 28.5 (26.7-30.3), PRR = 22.7, χ = 26218.4], loratadine[N = 516, ROR(95%CI) = 4.6 (4.2-5.0), PRR = 4.4, χ = 1378.1], desloratadine [N = 33, ROR(95%CI) = 6.1 (4.3-8.6), PRR = 5.8, χ = 131.9], fexofenadine [N = 498, ROR(95%CI) = 5.0 (4.6-5.5), PRR = 4.8, χ = 1519.0].
Neurological AEs associated with individual newer generation H1-antihistamines of interest varies a lot, whereas somnolence was the most common AE reports. Fexofenadine was highly associated with headaches. Sedative effects associated with levocetirizine and cetirizine should arouse more concern. Seizures significantly associated with levocetirizine and desloratadine were infrequently reported, further research is needed to avoid possible serious outcomes. Patients taking cetirizine probably have higher risk of dystonia and anticholinergic syndrome.
H1抗组胺药广泛用于治疗各种因组胺释放而产生症状的情况。然而，上市后监测研究报告了神经方面的不良事件，且从真实世界数据集中比较新一代H1抗组胺药相关神经疾病的文献有限。
我们对包括西替利嗪、氯雷他定、左西替利嗪、地氯雷他定和非索非那定在内的几种新一代H1抗组胺药与神经系统疾病进行了对比分析。
通过美国食品药品监督管理局不良事件报告系统，采用不成比例分析来确定与感兴趣的H1抗组胺药相关的可疑药物神经不良事件。使用比例报告率（PRR）、χ²（卡方）和具有95%置信区间（CI）的报告比值比（ROR）来估计关联性。
从FDA不良事件报告系统中提取了2017年至2021年43815例不良事件报告。我们研究中纳入的H1抗组胺药与各种神经不良事件相关，这些事件可分为12个方面，包含42个首选术语。大多数不良事件报告集中在嗜睡方面：西替利嗪[N = 1342，ROR（95%CI）= 11.8（11.2 - 12.5），PRR = 10.8，χ² = 11755.4]，左西替利嗪[N = 1276，ROR（95%CI）= 28.5（26.7 - 30.3），PRR = 22.7，χ² = 26218.4]，氯雷他定[N = 516，ROR（95%CI）= 4.6（4.2 - 5.0），PRR = 4.4，χ² = 1378.1]，地氯雷他定[N = 33，ROR（95%CI）= 6.1（4.3 - 8.6），PRR = 5.8，χ² = 131.9]，非索非那定[N = 498，ROR（95%CI）= 5.0（4.6 - 5.5），PRR = 4.8，χ² = 1519.0]。
与个别感兴趣的新一代H1抗组胺药相关的神经不良事件差异很大，而嗜睡是最常见的不良事件报告。非索非那定与头痛高度相关。左西替利嗪和西替利嗪的镇静作用应引起更多关注。与左西替利嗪和地氯雷他定显著相关的癫痫发作报告较少，需要进一步研究以避免可能的严重后果。服用西替利嗪的患者可能有更高的肌张力障碍和抗胆碱能综合征风险。
