Trimetazidine Induces Parkinsonism, Gait Disorders and Tremor

Massó, José-Félix Martí; Martí, Itxaso; Carrera, N; Jj, Poza; Munáin, Adolfo López de

doi:10.2515/therapie:2005061

Cited by 47 publications

(45 citation statements)

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“…Although the pathophysiology underlying TMZ-induced Parkinsonism remains unclear, a possible mechanism of action, as suggested by previous studies, involves the piperazine component in its chemical structure, similar to flunarizine, thiethylperazine, and perphenazine, that blocks striatal dopamine D2 receptors, thus resulting in an extrapyramidal type of adverse reaction [10,11,24,25]. Some studies have shown that the dopamine D2 receptor activity in the basal ganglia decreases in patients treated with drugs containing the piperazine ring [24,25].…”

Section: Discussionmentioning

confidence: 99%

“…Several previous studies have investigated DIP caused by antipsychotics [21,22], calcium channel blockers [17], and antiemetics [23]. Although DIP has been reported in patients treated with TMZ [10,11], little is known about the risk of Parkinsonism induced by TMZ.…”

Section: Discussionmentioning

confidence: 99%

“…While TMZ was found to be generally well tolerated in clinical trials, a number of recent studies have reported parkinsonism symptoms and exacerbation of Parkinson's disease as adverse drug reactions related to treatment with TMZ. Since the first case report of TMZ-induced parkinsonism by Marti Masso [9], a retrospective study [10] that was conducted using electronic records, has demonstrated TMZ-induced parkinsonism, gait disorder, and tremor in a few patients. Another study, a series of 21 cases of extrapyramidal disorders associated with TMZ, explained that interaction of TMZ's piperazine core with dopamine receptors leads to the disorders [11].…”

Section: Introductionmentioning

confidence: 99%

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Association between Trimetazidine and Parkinsonism: A Population-Based Study

Kwon

Kim

et al. 2019

Neuroepidemiology

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Background: The prevalence of drug-induced parkinsonism (DIP) has been reported with the use of trimetazidine (TMZ), an antianginal medication available in Asian and European countries. Very few studies have evaluated the association between DIP and TMZ use, and studies using population-based data from national databases are lacking. Objectives: To investigate the association between DIP and use of TMZ in patients with angina using data from a national healthcare claims database and to determine the predictive factors of DIP in TMZ use. Methods: A cross-sectional study was conducted on patients aged 40 years or more diagnosed with angina, using the Korean National Healthcare claims 2014 database. The association between TMZ use and DIP was evaluated using multivariate logistic regression analysis, adjusting for confounders, including age; sex; insurance type; comorbidities; and concurrent medications known to be commonly associated with DIP, such as typical and atypical antipsychotics. Results: Of the patients included in the study, 19% were prescribed TMZ. In addition, 2.5% of TMZ users had preexisting extrapyramidal and movement disorders. TMZ use was found to be a significant predictor of a new diagnosis of parkinsonism (adjusted OR [aOR] 1.39; 95% CI 1.06–1.81; p = 0.016). Age ≥65 years (aOR 2.07; 95% CI 1.13– 3.74; p = 0.017) and stroke as comorbid disease (aOR 3.23; 95% CI 1.87–5.61; p < 0.001) were also significantly associated with a new diagnosis of parkinsonism in TMZ users. Conclusions: Treatment with TMZ was a statistically significant predictor of a new diagnosis of parkinsonism. Efforts should focus on close monitoring of, and education on, TMZ use in relation to DIP in all patients who are prescribed TMZ, including those with preexisting extrapyramidal and movement disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association between Trimetazidine and Parkinsonism: A Population-Based Study

Kwon

Kim

et al. 2019

Neuroepidemiology

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“…It has been proved to be as good as propranolol (120-160 mg/day) and nifedipine (40 mg/day) in relieving anginal episodes and improving exercise tolerance [3]. However, trimetazidine may induce parkinsonism, or exaggerate previously diagnosed Parkinson's disease [16]. Parkison's symptoms may be resolved or improved after trimetazidine withdrawal [18].…”

Section: Discussionmentioning

confidence: 99%

Giant coronary aneurysm and arterial tortuosity

Yuan

2014

Folia Morphol

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“…However, retrospective studies have found an association between long-term use of trimetazidine and Parkinson syndrome, gait disturbances and tremor. 68,69 In the majority of cases, withdrawal of the drug leads to rapid resolution of these symptoms. 70 Further clinical trial data is required to determine the long-term safety of trimetazidine.…”

Section: Trimetazidine In Heart Failurementioning

confidence: 99%

The Role of Ivabradine and Trimetazidine in the New ESC HF Guidelins

Milinković

Rosano

Lopatin

et al. 2016

Cardiac Failure Review

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TherapeuticsAccess at: www.CFRjournal.com Chronic heart failure (HF), a complex and heterogeneous clinical syndrome, is a major cause of morbidity and mortality worldwide, and represents a major challenge to health care systems. The prevalence of HF and the number of hospitalisations is rising, even more in the ageing population.1 The direct costs of HF management reached 1-2 % of total health care expenditure and approximately two-thirds are attributable to hospitalisations. In 2012, in 197 countries, covering 99 % of the world's population, the overall cost of HF management was estimated at US$108 billion per annum, and is predicted to rise. 4 Around 60 % of total HF patients has HFrEF, which is associated with high reninangiotensin-aldosterone and sympathetic nervous systems activation.Most recent therapeutic improvements in these patients are due to the use of pharmacological agents that modulate these neuro-hormonal axes, angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta-blockers and mineralocorticoid receptor antagonists (MRAs). The beneficial effects of these treatments include the reduction of HF mortality by approximately one-third in a period of two decades. Despite this success, HF mortality rates remain high:the 5-year survival is worse than in many cancers. 5,6The 2016 European Society of Cardiology (ESC) HF guidelines recommend ACEI and beta-blockers as first-line therapy in symptomatic patients with HFrEF. 4 However, both registries and clinical reports underline that the treatment of HF patients is suboptimal much more than expected, and that the heart rate is increased despite beta-blocker therapy.7-12 The registry of 12,440 patients demonstrated heterogeneity in treatment strategies, due to the drug side effects and contraindications.7 A European registry 13 reported that only 17 % of patients were receiving the optimal combination and recommended dose of diuretic, ACEI and beta-blockers. Results from a French registry on 50,000 HF patients 14 also confirmed suboptimal treatment of HF, demonstrating that after the first month following hospitalisation for worsening HF, only 47 % received an ACEI, 54 % a beta-blocker, and 17 % MRAs. The I Brazilian Registry of Heart Failure (BREATHE) 15 , conducted in 57 hospitals in Brazil, revealed that 69 % of HF patients were receiving an ACEI or ARB, 60 % a beta-blocker, and 49 % MRAs. However, only 17 % were receiving all three drugs together. Therefore, a need to identify a novel pathways and strategies for HF treatment is obvious and clinically justified. This article reviews the clinical evidence and guidelines recommendations for the use of two novel therapies in HF: ivabradine and trimetazidine. AbstractThe prevalence of heart failure (HF) is increasing, representing a major cause of death and disability, and a growing financial burden on healthcare systems. Despite the use of effective treatments with both drugs and devices, mortality remains high. There is therefore a need for new and effective therapeutic a...

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Trimetazidine Induces Parkinsonism, Gait Disorders and Tremor

Cited by 47 publications

References 5 publications

Association between Trimetazidine and Parkinsonism: A Population-Based Study

Association between Trimetazidine and Parkinsonism: A Population-Based Study

Giant coronary aneurysm and arterial tortuosity

The Role of Ivabradine and Trimetazidine in the New ESC HF Guidelins

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