VASACARD-35 MR

Indications

• Stable angina pectoris

Dosage

Children: Refer to the BNF for Children for paediatric dosing information.

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Trimetazidine may inhibit mitochondrial 3-ketoacyl coenzyme A thiolase, leading to decreased long chain fatty acid β-oxidation while promoting glucose utilization in the myocardium. This shift in metabolic pathways helps to prevent a decrease in myocardial pH and contractility during ischemic events.

Pharmacodynamics

Trimetazidine is indicated for the symptomatic treatment of stable angina pectoris, particularly in patients who have not responded adequately to or are intolerant of first-line therapies. Caution is advised in patients with renal or hepatic impairment, as well as those with movement disorders, due to potential exacerbation of symptoms and increased risk of falls.

Pharmacokinetics

Trimetazidine is absorbed from the gastrointestinal tract with peak plasma concentrations typically occurring within 1 to 2 hours post-administration. It exhibits a high volume of distribution and is primarily eliminated via renal excretion. The drug has a half-life of approximately 5 to 7 hours, necessitating multiple doses throughout the day to maintain therapeutic levels.

Contra-indications

• Hypersensitivity to trimetazidine or any of its components
• Severe renal impairment
• Parkinsonism or other movement disorders

Adverse effects

• Dizziness
• Headache
• Nausea
• Abdominal pain
• Diarrhea
• Extrapyramidal symptoms
• Falls

Interactions

• May have additive effects with other medications that affect the central nervous system
• Potential for increased risk of extrapyramidal symptoms when used with antipsychotics or other dopaminergic agents

Precautions

• Use with caution in patients with renal or hepatic impairment
• Monitor for worsening of extrapyramidal symptoms or other movement disorders
• Counsel patients about the risk of falls

Pregnancy

Safety during pregnancy has not been established; use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is unknown whether trimetazidine is excreted in human milk; caution is advised.

Storage

Store in a cool, dry place, away from light and moisture. Keep out of reach of children.

Formulations

• Tablets

Mechanism of action

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.

Pharmacodynamics

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.