Carnovale Carla, Battini Vera, Gringeri Michele, Volonté Marina, Uboldi Maria Chiara, Chiarenza Andrea, Passalacqua Giovanni
Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, "Luigi Sacco" University Hospital, Università degli Studi di Milano, 20157, Italy.
Scientific Affairs Department, Sanofi, Milan, Italy.
World Allergy Organ J. 2022 Jul 2;15(7):100658. doi: 10.1016/j.waojou.2022.100658. eCollection 2022 Jul.
The change from prescription to over-the-counter (OTC) status of oral antihistamines may raise concerns about drug safety due to the possibility of misuse/abuse. In most European countries, oral antihistamines are available without prescription, whereas in Italy, only <10-tablet packs are available OTC.
To evaluate the safety profile of fexofenadine after OTC switch in Italy in a real-world setting, and to compare its safety profile to that of other European countries where larger pack sizes are available. To compare the safety of fexofenadine, cetirizine, and loratadine in Italy. To examine safety/efficacy across Europe with a systematic review.
This case-by-case analysis used the US Food and Drug Administration (FDA) adverse event reporting system (FAERS) to extract data of the adverse events (AEs) related to fexofenadine, loratadine and cetirizine in Italy January 2010-June 2020. The year 2016 was taken as the index date (removal of prescription requirement) for evaluation of the reporting trend of AEs of fexofenadine in Italy and make a comparison pre/post-OTC switch. A comparison of AEs with other European countries where fexofenadine is sold OTC in large packs >20 tablets (Belgium, Portugal, Switzerland, Finland, Hungary) was made. The rate at which an AE related to oral antihistamines occurred was estimated by calculation of the reporting rate (number of cases/[defined daily dose/1000 inhabitants per day]) on the basis of IQVIA sales data using the Italian Institute of Statistics database. A systematic review of the literature was also performed.
There were 3760 reports of AEs with a suspected association with fexofenadine; of these, eight were reported from Italy. There was a slightly increasing trend per year, in line with a general reporting trend of other drugs. In European countries where fexofenadine is available, the impact of OTC switch on AE reporting activity was negligible: from 2016, the reporting rate increased slightly and then normalized at 3.01, an incidence value similar to that recorded before the OTC switch (3.7 in 2015). Of 22 studies included in the systematic review, 18 (82%) positively evaluated the OTC use of oral antihistamines, confirming an acceptable safety/tolerability profile.
There was no difference in number of AEs reported for fexofenadine pre/post-OTC switch, indicating a similar safety profile. Spontaneous reporting systems are a valuable source of real-world data and support the OTC provision of oral antihistamines in Europe and fexofenadine in Italy, in addition to supporting the use of larger pack sizes in Italy.
口服抗组胺药从处方药变为非处方药（OTC）状态可能会因滥用/误用的可能性而引发对药物安全性的担忧。在大多数欧洲国家，口服抗组胺药无需处方即可获得，而在意大利，只有少于10片装的产品是非处方药。
评估在意大利非处方药转换后非索非那定在实际应用中的安全性概况，并将其安全性概况与其他有更大包装规格的欧洲国家进行比较。比较意大利非索非那定、西替利嗪和氯雷他定的安全性。通过系统评价研究欧洲各地的安全性/有效性。
本逐案分析使用美国食品药品监督管理局（FDA）不良事件报告系统（FAERS）提取2010年1月至2020年6月意大利与非索非那定、氯雷他定和西替利嗪相关的不良事件（AE）数据。将2016年作为索引日期（取消处方要求），以评估意大利非索非那定不良事件的报告趋势，并对非处方药转换前后进行比较。将不良事件与其他非索非那定以大于20片的大包装作为非处方药销售的欧洲国家（比利时、葡萄牙、瑞士、芬兰、匈牙利）进行比较。根据意大利统计局数据库的IQVIA销售数据，通过计算报告率（病例数/[限定日剂量/每千居民每日]）来估计与口服抗组胺药相关的不良事件发生率。还对文献进行了系统评价。
有3760份报告怀疑与非索非那定相关的不良事件；其中，有8份来自意大利。每年有轻微上升趋势，与其他药物的总体报告趋势一致。在有非索非那定的欧洲国家，非处方药转换对不良事件报告活动的影响可忽略不计：从2016年起，报告率略有上升，然后恢复正常，为3.01，这一发生率值与非处方药转换前记录的值（2015年为3.7）相似。在系统评价纳入的22项研究中，18项（82%）对口服抗组胺药的非处方药使用给予了积极评价，证实了其安全性/耐受性概况是可接受的。
非索非那定非处方药转换前后报告的不良事件数量没有差异，表明其安全性概况相似。自发报告系统是实际应用数据的宝贵来源，支持欧洲口服抗组胺药的非处方药供应以及意大利非索非那定的非处方药供应，此外还支持意大利使用更大包装规格。
