Cardimax (Trimetazidine)

Uses

Long-term treatment of Ischaemic heart disease (angina pectoris, sequelae of infarction).

Cardimax (Trimetazidine) is also used to associated treatment for these conditions: Angina Pectoris, Chronic Stable Angina Pectoris, Dizziness, Tinnitus, Decreased visual acuity caused by Vascular Disorders

How Cardimax (Trimetazidine) works

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. Cardimax (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.

Dosage

Cardimax (Trimetazidine) dosage

One 20 mg tablet thrice daily after meals. No dosage adjustments are required in patients with impaired renal and hepatic function.

One 35 mg modified release tablet twice daily at mealtimes in the morning and evening.

Side Effects

Cardimax (Trimetazidine) is safe and well tolerated. The most commonly encountered side effects are gastric discomfort, nausea, headache and vertigo. However, the side effects are mild and non-specific.

Toxicity

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.

Interaction

No drug interactions have so far been reported. In particular, no interactions of Cardimax (Trimetazidine) with beta-blockers, calcium antagonists, nitrates, heparin, hypolipidemic agents or digitalis have been reported.

Food Interaction

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

Volume of Distribution

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

Elimination Route

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.

Half Life

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.

Clearance

Cardimax (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.

Elimination Route

Cardimax (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%.

Pregnancy & Breastfeeding use

Pregnancy: Studies in animals have not demonstrated a teratogenic effect. However, in the absence of clinical data and for safety reasons, prescription should be avoided during pregnancy.

Nursing Mothers: There is no information on the secretion of Cardimax (Trimetazidine) into breast milk. However, breast feeding should be discontinued if the use of Cardimax (Trimetazidine) is considered essential.

Contraindication

Hypersensitivity to Cardimax (Trimetazidine) Dihydrochloride.

Storage Condition

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

Innovators Monograph

You find simplified version here Cardimax (Trimetazidine)