Janssen Research and Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA.
Adelphi Real World, Manchester, UK.
Clin Drug Investig. 2019 Nov;39(11):1057-1066. doi: 10.1007/s40261-019-00831-3.
Risk-minimization measures (RMM), including label revisions were implemented in Europe for domperidone because of evidence of increased incidence of cardiac arrhythmia and sudden cardiac death. In accordance with the guideline on good pharmacovigilance practices, the European Medicines Agency Pharmacovigilance Risk Assessment Committee requested to conduct two studies to evaluate the effectiveness of these risk minimization measures.
In Belgium, France, Germany, Spain, and the UK, surveys were conducted to assess physicians' knowledge on the updated domperidone labeling information, and a drug-utilization study (DUS) was conducted using healthcare databases to assess domperidone prescribing patterns before and after the RMM. Four DUS sensitivity analyses (scenarios) evaluated uncertainty regarding domperidone treatment duration and indication.
Among 1805 physicians participating in the survey, most were aware of the approved indication (nausea and vomiting, 80%), treatment duration (≤ 7 days, 70%), and maximum adult daily dose (10 mg three times daily, 84%). Only 33% selected the on-label indication from a list of indications for which they would prescribe domperidone. Awareness was low for medications contraindicated for concomitant use (26%) and contraindicated conditions (4%). In the DUS, under the optimistic scenario, a large improvement in labeling compliance from pre- to post-implementation period was observed in France (27% vs. 69%), while Belgium, Germany, Spain, and the UK showed small improvements (< 10%). In the other scenarios, there was little to no improvement in compliance with the revised labeling from the pre- to post-implementation periods in most countries.
The survey findings documented that most physicians in all five countries were aware of the main aspects of the revised labeling. Results of the DUS were inconclusive regarding the effect of the RMM and compliance with the revised labeling for all countries except France.
由于有证据表明多潘立酮会增加心律失常和心源性猝死的发生率，因此在欧洲采取了风险最小化措施（RMM），包括标签修订。根据良好药物警戒实践指南，欧洲药品管理局药物警戒风险评估委员会要求开展两项研究，以评估这些风险最小化措施的有效性。
在比利时、法国、德国、西班牙和英国，开展了调查，以评估医生对更新后的多潘立酮标签信息的了解情况，还利用医疗保健数据库开展了药物利用研究（DUS），以评估 RMM 实施前后多潘立酮的处方模式。四项 DUS 敏感性分析（方案）评估了多潘立酮治疗持续时间和适应证不确定的情况。
在参与调查的 1805 名医生中，大多数人了解多潘立酮的批准适应证（恶心和呕吐，80%）、治疗持续时间（≤7 天，70%）和最大成人日剂量（10 毫克，每日 3 次，84%）。只有 33%的医生从他们会开具多潘立酮的适应证列表中选择了适应证。对于禁止同时使用的药物（26%）和禁忌证（4%）的认知度较低。在 DUS 中，在乐观方案下，法国的标签合规性从实施前到实施后有很大的改善（27%比 69%），而比利时、德国、西班牙和英国的改善幅度较小（<10%）。在其他方案中，除法国外，大多数国家从实施前到实施后，修订后的标签合规性几乎没有改善。
调查结果表明，所有五个国家的大多数医生都了解修订标签的主要内容。除法国外，DUS 的结果对 RMM 的效果和修订后标签的合规性在所有国家均没有明确的结论。
