Trimetazidine
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| Systematic (IUPAC) name | |
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1-(2,3,4-trimethoxybenzyl)piperazine
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| Clinical data | |
| Trade names | Vastarel |
| AHFS/Drugs.com | International Drug Names |
| Legal status |
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| Routes of administration |
Oral |
| Pharmacokinetic data | |
| Bioavailability | completely absorbed at around 5 hours, steady state is reached by 60th hour |
| Protein binding | low (16%) |
| Metabolism | minimal |
| Biological half-life | 7 to 12 hours |
| Excretion | mainly renal (unchanged), exposure is increased in renal impairment - on average by 4-fold in subjects with severe renal impairment (CrCl <30 ml/min) |
| Identifiers | |
| CAS Number | 5011-34-7  |
| ATC code | C01EB15 (WHO) |
| PubChem | CID: 21109 |
| ChemSpider | 19853  |
| UNII | N9A0A0R9S8 |
| ChEMBL | CHEMBL203266 |
| Chemical data | |
| Formula | C14H22N2O3 |
| Molecular mass | 266.336 g/mol |
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Trimetazidine is a drug for angina pectoris sold under the brand name Vastarel MR. Trimetazidine is described as the first cytoprotective anti-ischemic agent developed and marketed by Laboratoires Servier (France). Trimetazidine is an anti-ischemic (anti-anginal) metabolic agent, which improves myocardial glucose utilization through inhibition of fatty acid metabolism, also known as fatty acid oxidation inhibitor.
Contents
Medical uses
Trimetazidine usually prescribed as a long-term treatment of angina pectoris, and in some countries (including France) for tinnitus and dizziness. It is taken twice a day. In 2012 European Medicines Agency (EMA) finished a review of benefits and risks of trimetazidine and recommended restricting use of trimetazidine-containing medicines just as an additional treatment of angina pectoris in case of inadequate control by or intolerance to first-line antianginal therapies.[1]
Controlled studies in angina patients have shown that trimetazidine increases coronary flow reserve, thereby delaying the onset of ischemia associated with exercise, limits rapid swings in blood pressure without any significant variations in heart rate, significantly decreases the frequency of angina attacks, and leads to a significant decrease in the use of nitrates.
It improves left ventricular function in diabetic patients with coronary heart disease. Recently, it has been shown to be effective in patients with heart failure of different etiologies.[2][3]
Adverse effects
Trimetazidine has been treated as a drug with a high safety and tolerability profile.[4] It interacts with monoamine oxidase inhibitors.
There is scarce information about trimetazidine's effect on mortality, cardiovascular events or quality of life. Long term randomized controlled trials comparing trimetazidine against standard anti-anginal agents, using clinically important outcomes would be justifiable.[5] Recently, an international multicentre retrospective cohort study has indeed shown that in patients with heart failure of different etiologies, the addition of trimetazidine on conventional optimal therapy can improve mortality and morbidity.[6]
EMA recommends that doctors should no longer prescribe trimetazidine for the treatment of patients with tinnitus, vertigo or disturbances in vision.[1] The recent EMA evaluation also revealed high potential for Parkinsonian (or extrapyramidal) symptoms (such as tremor, rigidity, akinesia, hypertonia), gait instability, restless leg syndrome, other related movement disorders, reversible after treatment discontinuation. As a consequence, doctors are advised not to prescribe the medicine either to patients with Parkinson disease, parkinsonian symptoms, tremors, restless leg syndrome or other related movement disorders, nor to patients with severe renal impairment.[1]
Mechanism of action
Trimetazidine inhibits beta-oxidation of fatty acids by blocking long-chain 3-ketoacyl-CoA thiolase, which enhances glucose oxidation.[7] In an ischaemic cell, energy obtained during glucose oxidation requires less oxygen consumption than in the beta-oxidation process. Potentiation of glucose oxidation optimizes cellular energy processes, thereby maintaining proper energy metabolism during ischaemia. By preserving energy metabolism in cells exposed to hypoxia or ischaemia, trimetazidine prevents a decrease in intracellular ATP levels, thereby ensuring the proper functioning of ionic pumps and transmembrane sodium-potassium flow whilst maintaining cellular homeostasis.[8]
Brand names
Distributed as: Vastarel MR, Vastarel 20 mg, Vastarel LM, Vastarel LP, Preductal MR, Flavedon MR, Trivedon MR 35 mg (Cipla Ltd.), Flavedon 20 mg, Cardaptan, Idaptan, Carvidon MR, Trizedon MR, Vestar, Carmetadin, Metacard MR, Angirid MR, and others.
References
- ↑ 1.0 1.1 1.2 Lua error in package.lua at line 80: module 'strict' not found.
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- ↑ Ciapponi A1, Pizarro R, Harrison J. Trimetazidine for stable angina.Cochrane Database Syst Rev. 2005 Oct 19;(4):CD003614
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Fragasso G, Rosano G, Baek Hong S, Sisakian H, Di Napoli P, Alberti L, Calori G, Kang SM, Sahakyan A, Vitale C, Marazzi G, Margonato A, Belardinelli R. Effect of partial acid oxidation inhibition with trimetazidine on mortality and morbidity in heart failure: results from an international multicentre retrospective cohort study. Int J Cardiol. 2013;163:320-5.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
Further reading
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