By Marcello Cherchi, MD PhD
For patients
Trimetazidine was originally used for certain heart conditions. Small studies suggest it might help patients with Ménière’s disease. One the risks of trimetazidine is that it can cause or worsen parkinsonism. Trimetazidine is not available in the United States.
For clinicians
Overview
Trimetazidine is a piperazine derivative that was originally studied in the management of stable angina pectoris; studies suggest that its inhibition of fatty acid oxidation has cytoprotective effects, and there is some evidence that it also works as an antagonist at AMPA/kainite receptors. Limited evidence suggests that trimetazidine has similar efficacy to betahistine in the management of Ménière’s disease, and perhaps “cochleovestibular disorders of ischemic origin.” Trimetazidine can induce parkinsonism and other movement disorders.
Introduction
Trimetazidine is a piperazine derivative that was originally studied in the management of stable angina pectoris; studies suggest that its inhibition of fatty acid oxidation has cytoprotective effects, and there is some evidence that it also works as an antagonist at AMPA/kainite receptors. Limited evidence suggests that trimetazidine has similar efficacy to betahistine in the management of Ménière’s disease.
Pharmacology
Trimetazidine is a piperazine derivative that was originally studied in the management of stable angina pectoris, where it is believed to have cytoprotective effects by inhibiting fatty acid oxidation, thereby improving glucose utilization by myocardial cells, reducing the risk of ischemia. Animal studies suggest that it also works as an antagonist at AMPA/kainite receptors in the vestibular ganglion (Dayanithi et al. 2007).
Adverse effects
As of this writing, the FDA Adverse Events Reporting System (FAERS) listed the most common side effects as fatigue, fever, “general physical health deterioration,” edema and gait disturbance.
Cautions and contraindications
Trimetazidine can worsen symptoms of parkinsonism (Kim et al. 2020; Kwon et al. 2019; Pinter et al. 2020; Sommet et al. 2005) and other movement disorders (Marti Masso et al. 2005), and is thus contraindicated for patients with those diagnoses.
Relevance in otoneurology
Limited studies found trimetazidine’s efficacy to be similar to betahistine in the management of Ménière’s disease (Kluyskens et al. 1990; Martini and De Domenico 1990). One placebo-controlled study of 45 patients with undifferentiated “cochleovestibular disorders of ischemic origin” reported trimetazidine as superior to placebo (Coyas 1990). These limited data suggest that trimetazidine may be relevant for peripheral, rather than central, vestibular disorders.
Other notes
Trimetazidine is currently not FDA-approved.
References
Coyas A (1990) [The efficacy of trimetazidine in cochleovestibular disorders of ischemic origin. A crossover control versus placebo trial]. Ann Otolaryngol Chir Cervicofac 107 Suppl 1: 82-7.
Dayanithi G, Desmadryl G, Travo C, Chabbert C, Sans A (2007) Trimetazidine modulates AMPA/kainate receptors in rat vestibular ganglion neurons. Eur J Pharmacol 574: 8-14. doi: 10.1016/j.ejphar.2007.07.003
Kim S, Yu YM, Kwon J, Jeong KH, Lee JS, Lee E (2020) Trimetazidine Use and the Risk of Parkinsonism: A Nationwide Population-Based Study. Int J Environ Res Public Health 17. doi: 10.3390/ijerph17197256
Kluyskens P, Lambert P, D’Hooge D (1990) [Trimetazidine versus betahistine in vestibular vertigo. A double blind study]. Ann Otolaryngol Chir Cervicofac 107 Suppl 1: 11-9.
Kwon J, Yu YM, Kim S, Jeong KH, Lee E (2019) Association between Trimetazidine and Parkinsonism: A Population-Based Study. Neuroepidemiology 52: 220-226. doi: 10.1159/000497613
Marti Masso JF, Marti I, Carrera N, Poza JJ, Lopez de Munain A (2005) Trimetazidine induces parkinsonism, gait disorders and tremor. Therapie 60: 419-22. doi: 10.2515/therapie:2005061
Martini A, De Domenico F (1990) [Trimetazidine versus betahistine in Meniere’s disease. A double blind method]. Ann Otolaryngol Chir Cervicofac 107 Suppl 1: 20-7.
Pinter D, Juhasz A, Harmat M, Janszky J, Kovacs N (2020) The Impact of Trimetazidine on Disease Severity and Quality of Life in Parkinson’s Disease. Sci Rep 10: 10050. doi: 10.1038/s41598-020-66692-5
Sommet A, Azais-Vuillemin C, Bagheri H, Rascol O, Montastruc JL (2005) Trimetazidine: a new cause for drug-induced parkinsonism? Mov Disord 20: 1080-1. doi: 10.1002/mds.20574
