Introduction
Trimetazidine hydrochloride is a 3-ketoacyl Co-A thiolase inhibitor (3-KAT) with a cytoprotective effect in cells exposed to ischemia and hypoxia.

Composition Each film coated tablet contains
Trimetazidine hydrochloride BP 20 mg.

Pharmacology
Trimetazidine, known for years to be an effective antianginal agent, shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. By decreasing fatty acid oxidation, trimetazidine stimulates glucose utilization, restoring coupling between glycolysis and carbohydrate oxidation and leading to adenosine triphosphate production with lesser oxygen consumption. The antianginal properties of this agent are devoid of haemodynamic changes, and dramatically improve recovery of mechanical function after ischemia.

Mechanism of action
Trimetazidine inhibits mitochondrial long-chain 3-KAT thus favoring glucose oxidation at the expense of fatty acid oxidation, which is impaired. Glucose and fatty acid metabolism in the heart after the formation of acetyl Co-A, both processes follow a common pathway, whereas glucose is able to continue with glycolysis. Oxidation of fatty acids impairs pyruvate oxidation. Trimetazidine suppresses fatty acid oxidation via inhibition of the enzyme 3-KAT, and enhances the process of glucose oxidation. The decrease in fatty acid oxidation

and the stimulation of glucose oxidation provoked by trimetazidine improve the coupling between glycolysis and
carbohydrate oxidation. Accordingly, ATP production is achieved with consumption of less oxygen. Moreover, trimetazidine stimulates membrane phospholipid turnover during ischemia, thus redirecting fatty acids toward phospholipids.

Indication
1. Ischemic heart disease (Angina pectoris, Sequelae of infarction)
2. Adjuvant symptomatic treatment of vertigo and tinnitus
3. Adjuvant symptomatic treatment of the decline visual acuity and visual field disturbances, presumably of vascular origin

Dosage and Administration
One tablet thrice daily after meal.

Contraindication
Trimetazidine hydrochloride has no contraindications except hypersensitivity to Trimetazidine hydrochloride and can therefore be prescribed even when other antianginal agents are contraindicated.

Side Effects
Trimetazidine hydrochloride is safe & well tolerated. In addition, the toxic dose being very

high, the safety margin of this drug is wide. The most commonly encountered side effects are gastric discomfort, nausea, headache and vertigo.

Use in Renal impairment
The active substance of Trimetazidine hydrochloride is essentially eliminated in urine in unchanged form and in the form of metabolites. The usual dose is therefore used in coronary patients with moderate renal failure. There is no need for dose adaptation in renal failure. In contrast, Trimetazidine hydrochloride has not been studied in dialysis patients.

Use in Hepatic impairment
No need for dose adaptation in a patient with hepatic impairment.

Use in Elderly patients
Trimetazidine (Anginox) is a suitable choice for elderly coronary patients. The haemodynamic side effects and drug interactions can be frequent and severe in elderly due to reduced creatinine clearance or liver metabolism, but Trimetazidine is devoid of any direct hemodynamic effects.

Use in Pregnancy & Lactation
Teratogenesis studies have shown that Trimetazidine hydrochloride administered per os at doses of up to 100 mg/kg had no teratogenic potential in animals. Trimetazidine hydrochloride has also been extensively used in some countries, and Japan in particular, without any teratogenic effect has been found. In view of its safety, Trimetazidine hydrochloride is not included in any restricted list nor is it contraindicated in pregnant women. However it is preferable not to prescribe it during pregnancy as a precaution.

There is no information on the secretion of Trimetazidine into breast milk. However beast feeding should be discontinued if the use of trimetazidine is considered essential.

Use in Children
Safety & efficacy has not been established.

Drug interactions
No drug interactions have been reported.

Over dosage
The toxic dose being very high, the safety margin of this drug is wide.

How Supplied
Each box contains 3 blister packs of 10 tablets