Unité de Neurologie-Neuropharmacovigilance, Service de Pharmacologie Clinique, CHU Amiens, France.
Fundam Clin Pharmacol. 2012 Apr;26(2):198-203. doi: 10.1111/j.1472-8206.2011.01008.x. Epub 2011 Nov 2.
Over the last few years, a number of cases of extrapyramidal disorders associated with trimetazidine (TMZ) use has been reported. Here, we report on a series of 21 cases. All but one of the patients (mean age 74) had been taking TMZ for several years. The indication for prescription of TMZ could not be identified in seven cases. The TMZ-associated adverse drug reactions were typical parkinsonism (akinesia and/or rigidity and/or rest tremor) in 17 cases, gait disorders in three cases (one with orthostatic tremor), and restless leg syndrome in one case. Discontinuation of TMZ led to complete disappearance of the symptoms in 16 cases and a significant reduction in the five other patients. TMZ has the same piperazine core as the dopamine antagonists flunarizine and cinnarizine (both of which have been reported to induce extrapyramidal symptoms). Hence, striatal D2 receptor blockade could result in the onset or the worsening of extrapyramidal disorders. Even though this adverse drug reaction is now listed in TMZ's Summary of Product Characteristics (because of the initial reports), the risk remains poorly known by clinicians. There is a need to raise awareness of this phenomenon and to reassess TMZ 's risk-benefit ration, especially in the elderly.
在过去的几年中，已经报道了一些与曲美他嗪（TMZ）使用相关的锥体外系疾病的病例。在这里，我们报告了一系列 21 例病例。除了一名患者（平均年龄 74 岁）外，所有患者都已经使用 TMZ 多年。在七个病例中，无法确定 TMZ 处方的适应证。TMZ 相关的不良反应在 17 例中为典型帕金森病（运动不能和/或僵硬和/或静止性震颤），3 例为步态障碍（1 例伴有直立性震颤），1 例为不安腿综合征。停止使用 TMZ 后，16 例患者的症状完全消失，另外 5 例患者的症状明显减轻。TMZ 具有与多巴胺拮抗剂氟桂利嗪和肉桂嗪相同的哌嗪核心（两者都已被报道可引起锥体外系症状）。因此，纹状体 D2 受体阻断可能导致锥体外系疾病的发作或恶化。尽管这种不良反应现在已经在 TMZ 的产品特性摘要中列出（因为最初的报告），但临床医生对这种风险仍然知之甚少。有必要提高对这种现象的认识，并重新评估 TMZ 的风险效益比，尤其是在老年人中。
