Vascare Tablet

Trimetazidine is a metabolic antianginal agent used as an adjunctive treatment for stable angina pectoris in patients who are inadequately controlled with or intolerant to first-line antianginal therapies. It improves the efficiency of cardiac energy metabolism during ischemia without significantly affecting heart rate or blood pressure.

Trimetazidine is thought to reduce fatty acid oxidation and promote glucose oxidation, helping to protect myocardial cells from ischemic injury and improve exercise tolerance in patients with chronic stable angina.

Trimetazidine is a piperazine derivative indicated as an adjunct therapy in symptomatic treatment of stable angina pectoris.

Trimetazidine is indicated for the symptomatic treatment of stable angina pectoris in patients inadequately controlled or intolerant to first line therapies.

• Angina Pectoris
• Chronic Stable Angina Pectoris
• Dizziness
• Tinnitus
• Decreased visual acuity caused by Vascular Disorders

Trimetazidine is indicated for the symptomatic treatment of stable angina pectoris in patients inadequately controlled or intolerant to first line therapies. Patients should be counselled regarding the risk of use with reduced renal or hepatic function, worsening of extrapyramidal symptoms or other movement disorders, and risk of falls.

During myocardial ischemia, anaerobic metabolism takes over, increasing levels of lactic acid. The decreased intracellular pH and increased concentration of protons activates sodium-hydrogen and sodium-calcium antiport systems, raising intracellular calcium concentrations, finally leading to decreased contractility.

This injury to the myocardium raises concentrations of catecholamines, which activate hormone sensitive lipase, and increasing fatty acid concentrations in plasma. When the myocardium is repurfused, fatty acid oxidation becomes the dominant form of ATP production, maintaining an acidic pH, and further exacerbating the injury.

The mechanism of action of trimetazidine is not fully understood. Trimetazidine may inhibit mitochondrial 3-ketoacyl coenzyme A thiolase, decreasing long chain fatty acid β-oxidation but not glycolysis in the myocardium. The decreased long chain fatty acid β-oxidation is compensated for by increased use of glucose, preventing a lowered myocardial pH, and further decreases in contractility. However, another study suggests that 3-ketoacyl coenzyme A thiolase may not be trimetazidine's target, and that this mechanism may be incorrect.

In elderly patients, a 35 mg oral modified release tablet reaches a mean C_max of 115 µg/L, with a T_max of 2.0-5.0 hours, and a mean AUC_0-12 of 1104 h*µg/L. In young, healthy patients, the same dose reaches a mean C_max of 91.2 µg/L, with a T_max of 2.0-6.0 hours, and an AUC_0-12h 720 h*µg/L.

The volume of distribution of trimetazidine is 4.8 L/kg.

Trimetazidine is 15% protein bound in plasma. Trimetazidine can bind to human serum albumin.

Trimetazidine is 79-84% eliminated in the urine, with 60% as the unchanged parent compound. In a study of 4 healthy subjects, individual metabolites made up 0.01-1.4% of the dose recovered in urine. In the urine, 2-desmethyltrimetazidine made up 0-1.4% of the recovered dose, 3- and 4-desmethyltrimetazidine made up 0.039-0.071% each, N-methyltrimetazidine made up 0.015-0.11%, trimetazidine ketopiperazine made up 0.011-0.4%, N-formyltrimetazidine made up 0.035-0.42%, N-acetyltrimetazidine made up 0.016-0.19%, desmethyl trimetazidine O-sulphate made up 0.01-0.65%, and an unknown metabolite made up0.026-0.67%.

In young, healthy subjects, the half life of trimetazidine is 7.81 hours. In patients over 65, the half life increases to 11.7 hours.

Trimetazidine clearance is strongly correlated with creatinine clearance. In eldery patients with a creatinine clearance of 72 ± 8 mL/min, trimetazidine clearance was 15.69 L/h. In young, healthy patients with a creatinine clearance of 134 ± 18 mL/min, trimetazidine clearance was 25.2 L/h.

Data regarding overdoses of trimetazidine are not readily available. Treat overdoses with symptomatic and supportive therapy.

The oral LD₅₀ in rats is 1700 mg/kg, and in mice is 1550 mg/kg. The subcutaneous LD₅₀ in rats is 1500 mg/kg, and in mice is 410 mg/kg.

• Take with food. Take during a meal.
• Take with plain water. Take with a glass of water.