DataSheet1_A systematic review of flurbiprofen 8.75 mg dose and risk of adverse events (excluding haemorrhagic) resulting from drug-drug interactions.PDF

Background: Flurbiprofen 8.75 mg lozenges and oromucosal sprays are used for symptomatic relief of sore throat in patients aged 12 years and over. The documented adverse events of flurbiprofen use include those related to its pharmacological actions, namely, increased risk of haemorrhagic events, however other adverse events (such as nephrotoxicity and cardiac failure) have been known to occur. The likelihood of occurrence of adverse events increases when flurbiprofen is used concomitantly with some other medications. Therefore, the objective of this systematic review was to collate the current evidence on adverse events which occur with flurbiprofen 8.75 mg dose (any formulation), in particular as a result of interaction with other medicinal products, with a focus on non-haemorrhagic events.
Methods: Systematic searches of the literature were conducted to identify literature on any formulation of flurbiprofen 8.75 mg up to the date of the electronic database search (data lock: 28 April 2020). Publications were screened to identify studies reporting non-haemorrhagic adverse events with flurbiprofen 8.75 mg and/or non-haemorrhagic adverse events in the comparator arm. Data extraction was performed for eligible studies according to pre-defined criteria and summarised in narratives, tables and figures. Risk of bias and certainty of evidence assessments were planned for each included study where results relating to the primary objective of the systematic review were available.
Results: Of 1,528 publications identified by systematic literature searches, 26 met the inclusion criteria and were included in this review. None of these 26 studies contained information on non-haemorrhagic adverse events occurring as a result of a drug-drug interaction (interaction with concomitant medication used with flurbiprofen 8.75 mg), as per the primary objective and secondary objectives of the systematic review.
Conclusion: Results from this systematic review on the risk of non-haemorrhagic events did not provide evidence for these events occurring as a result of interaction with other medicinal products. Additional appropriately designed studies would be required to confirm whether these findings suggest a true absence of risk or limitations in reporting.

背景：8.75mg氟比洛芬（flurbiprofen）含片与口腔黏膜喷雾剂，用于12岁及以上患者咽痛的对症缓解。目前已记录的氟比洛芬不良事件包括与其药理作用相关的事件，即出血事件风险升高；此外也有报道称可发生其他不良事件（如肾毒性与心力衰竭）。当氟比洛芬与部分其他药物联合使用时，不良事件的发生风险会进一步增加。因此本系统评价的目标为整理当前关于8.75mg剂量氟比洛芬（任何剂型）相关不良事件的现有证据，尤其聚焦于与其他药品相互作用导致的不良事件，重点关注非出血性不良事件。
方法：系统检索截至电子数据库检索日期（数据锁定日期：2020年4月28日）的所有关于8.75mg氟比洛芬任何剂型的文献。对检索到的出版物进行筛选，以识别报道8.75mg氟比洛芬非出血性不良事件，以及/或对照组非出血性不良事件的研究。根据预先设定的标准对符合纳入标准的研究开展数据提取工作，并以叙述性文字、表格及图表进行汇总。针对每一项纳入研究，若其具备本系统评价主要目标相关的结果数据，则计划对其进行偏倚风险与证据确定性评估。
结果：系统文献检索共识别出1528篇文献，其中26篇符合纳入标准并被纳入本次评价。根据本系统评价的主要及次要目标，这26项研究均未提及因药物相互作用（即与8.75mg氟比洛芬联用的伴随药物之间的相互作用）引发的非出血性不良事件相关信息。
结论：本系统评价针对非出血性不良事件风险的研究结果，未提供此类事件由与其他药品相互作用引发的证据。需开展更多设计规范的研究，以明确本研究结果是提示此类风险确实不存在，还是仅由研究报告的局限性所致。