Composition:

Metacardia: Each film-coated tablet contains 20.6 mg trimetazidine dihydrochloride equivalent to 20 mg trimetazidine.

Metacardia MR: Each modified release film-coated tablet contains 35 mg trimetazidine dihydrochloride.

Pharmacodynamics:

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 reperfused, fatty acid oxidation becomes the dominant form of ATP production, maintaining an acidic pH, and further exacerbating the injury.

 Metacardia, Trimetazidine, inhibits B-oxidation of fatty acids by blocking long-chain 3-ketoacyl-CoA thiolase, which enhances glucose oxidation.

In an ischemic cell, energy obtained during glucose oxidation requires less oxygen consumption than in the B-oxidation process. 

Potentiation of glucose oxidation optimizes cellular energy processes, thereby maintaining proper energy metabolism during ischemia.

In patients with ischemic heart disease, trimetazidine acts as a metabolic agent, preserving the myocardial high-energy phosphate intracellular levels.  Anti-ischaemic effects are achieved without concomitant haemodynamic effects.

Pharmacokinetics:

It is well absorbed and metabolized in the liver to inactive metabolites, then excreted in urine with a half life of 5-6 hours.

Therapeutic Indications:

Metacardia, Metacardia MR are indicated in adults as second line add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line anti-anginal therapies.

Dosage and Administration:

Oral route.

Metacardia: The usual dose is two to three tablets daily to be taken with meals.

Metacardia MR: The usual dosage is one tablet in the morning and evening with meals.

Tablets should be swallowed with a glass of water at meal times.

If you think that the effect is too strong or too weak, talk to your doctor or pharmacist.

For kidney problems or patients older than 75 years old, the doctor may adjust the recommended dose.

Overdose:

Consult a doctor or a pharmacist immediately.

What to do in case one or several doses have been missed?:

Resume treatment normally.

Do not take a double dose to compensate the forgotten single dose.

Very limited information is available on trimetazidine overdose.

Treatment should be symptomatic.

Drug-drug Interactions:

Ask the doctors or pharmacist s advice before taking any medicine.

No drug-drug interactions have been identified.

Precautions:

This medicine not recommended during breastfeeding.

This medicine is not a curative treatment for angina attacks, nor an initial treatment for unstable angina pectoris or for myocardial infarction.

In the event of an angina attack, inform the doctor. Tests may be required and the treatment

may possibly be modified.

This medicine can cause or worsen symptoms such as trembling, rigid posture, slow movements and a shuffling, unbalanced walk, especially in elderly patients which should be investigated and reported to your doctor who could re-assess the treatment.

Falls may occur following a drop in blood pressure or loss of balance.

Children:

Trimetazidine dihydrochloride modified release film-coated tablet, is not recommend in children aged below 18 years.

Taking other medicines:

Informe the doctor or pharmacist if you are taking, or have recently taken any other medicines, even if it is a medicine without a prescription.

Pregnancy:

It is preferable no to take this medicine during pregnancy.

If you discover that you are pregnant whilst taking this medicine, consult the doctor as he alone can judge the necessity of continuing your treatment.

In the absence of clinical data, the risk of malformation cannot be excluded. Therefore, for safety reasons, prescription should be avoided during pregnancy.

Lactation:

In the absence of data on excretion in breast milk, breast-feeding is not recommended during treatment.

If you are pregnant or breast-feeding, think you may to be pregnant or are planning to have baby, ask the doctor or pharmacist for advice before taking this medicine.

Effects on the ability to drive or use machines:

Trimetazidine can cause dizziness or drowsiness which may affect the ability to drive or use machines.

Contraindications:

Do not take Metacardia, Metacardia MR if you are allergic to Trimetazidine or any of the other ingredients of the medicine.

Parkinson disease: Disease of the brain affecting movement (trembling, rigid posture, slow movements and shuffling, unbalanced walk).

Severe kidney problems.

Adverse Reactions:

As with all drugs, trimetazidine is likely to have undesirable effects under the following frequency:

Very common (>1/10).

Common (>1/100, <1/10).

Uncommon (>1/1000, <1/100).

Rare (>1/10000, <1/1000).

Very rare (<1/10000).

Not known (cannot be estimated from the available data).

Common: Dizziness, headache, abdominal pain, diarrhea, indigestion, feeling sick, vomiting, rash, itching, hives and feeling of weakness.

Rare: Fast or regular heartbeats (also called palpitations), extra heartbeats, faster heartbeat, fall in blood pressure on standing-up which causes dizziness, light headiness or fainting, malaise (generally feeling unwell), dizziness, fall, flushing.

Not known: Extrapyramidal symptoms (unusual movements, including trembling and shaking of the hands and fingers, twisting movements of the body, shuffling walk and stiffness of the hands and fingers, twisting movements of the body, shuffling walk and stiffness of the arms and legs), usually reversible treatment discontinuation.

Sleep disorders (difficulty in sleeping, drowsiness), constipation, serious generalized red skin rash with blistering, swelling of face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing.

Severe reduction in number of white blood cells which makes infections more likely, reduction in blood platelets, which increases risk of bleeding or bruising.

A liver disease (nausea, vomiting, loss of appetite, feeling generally unwell, fever, itching, yellowing of the skin and eyes, light coloured bowel motions, dark coloured urine).

If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in the leaflet.

Presentation & Storage:

Metacardia tablets: are supplied in boxes of 2 (Al/transparent PVC) blisters of 10 film-coated tablets each + insert leaflet.

Metacardia MR tablets: are supplied in boxes of  3 (Al/transparent PVC) blisters of 10 modified release film-coated tablets each + insert leaflet.

Store at temperature not exceed 30°C, in dry a place.