Riley J, Wilton L V, Shakir S A W
Drug Safety Research Unit, Southampton, UK.
Int J Clin Pharmacol Ther. 2002 Jun;40(6):241-8. doi: 10.5414/cpp40241.
To conduct a post-marketing observational cohort study to assess the safety of mibefradil in the community, using Prescription-Event Monitoring (PEM).
Data were collected and analyzed on patients prescribed mibefradil by 1,996 General Practitioners (GPs) throughout England. Incidence densities were calculated for all reported events and selected events were followed-up by means of further questionnaires.
The study was terminated early due to the voluntary withdrawal of mibefradil from the market because of potential drug interactions. A cohort of 3,085 patients was recruited, with a mean age of 64.5 years. The major indication for use was hypertension (55% of the cohort), the indication was not specified in 33% of patients. 80% of GPs expressing an opinion rated mibefradil as effective. The major reason for stopping was withdrawal from the market (2,342 patients). The commonest reported adverse events and reasons for stopping were malaise/lassitude, dizziness, edema and headache. Seven clinically serious reports of bradycardia/collapse were considered to be possible adverse drug reactions (ADRs) to mibefradil. All were in the elderly (> 65 years), 6 were considered to be a result of possible drug interactions. In total, 11 possible drug interactions occurred. Nine (8 reports of bradycardia and 1 of syncope) involved beta-blockers. Another, a report of collapse and severe bradycardia, occurred in a patient who had started a dihydropyridine calcium channel blocker within 24 hours of stopping mibefradil and the other was a report of palpitations and dyspnea in a patient on concomitant digoxin and sotalol. None of the 53 deaths occurring during the study was attributed to mibefradil.
Mibefradil was only available on the UK market for 6 months before it was withdrawn from the market because of potential drug interactions. With respect to the reasons leading to its withdrawal, in this cohort of 3,085 patients, 11 possible drug interactions were detected (6 clinically significant) involving beta-blockers, a dihydropyridine calcium channel blocker and digoxin and/or sotalol. PEM can contribute to the understanding of ADRs caused by drug interactions occurring in real-life settings.
采用处方事件监测（PEM）进行一项上市后观察性队列研究，以评估米贝拉地尔在社区中的安全性。
收集并分析了全英格兰1996名全科医生（GP）为患者开具米贝拉地尔的相关数据。计算所有报告事件的发病密度，并通过进一步问卷调查对选定事件进行随访。
由于米贝拉地尔因潜在药物相互作用而自愿退出市场，该研究提前终止。招募了3085名患者组成队列，平均年龄为64.5岁。主要使用指征为高血压（占队列的55%），33%的患者未明确说明指征。80%发表意见的全科医生认为米贝拉地尔有效。停药的主要原因是退出市场（2342名患者）。报告的最常见不良事件及停药原因是不适/倦怠、头晕、水肿和头痛。七例关于心动过缓/虚脱的临床严重报告被认为可能是米贝拉地尔的药物不良反应（ADR）。所有病例均为老年人（>65岁），6例被认为可能是药物相互作用的结果。总共发生了11例可能的药物相互作用。9例（8例心动过缓报告和1例晕厥报告）涉及β受体阻滞剂。另一例，一名患者在停用米贝拉地尔24小时内开始使用二氢吡啶类钙通道阻滞剂后出现虚脱和严重心动过缓报告，还有一例报告是一名同时服用地高辛和索他洛尔的患者出现心悸和呼吸困难。研究期间发生的53例死亡均与米贝拉地尔无关。
米贝拉地尔在英国市场仅上市6个月就因潜在药物相互作用而退出市场。就其退出市场的原因而言，在这个由3085名患者组成的队列中，检测到11例可能的药物相互作用（6例具有临床意义），涉及β受体阻滞剂、二氢吡啶类钙通道阻滞剂以及地高辛和/或索他洛尔。处方事件监测有助于了解现实生活中由药物相互作用引起的药物不良反应。
