Trimektal^® (Tablets) Instructions for Use

ATC Code

C01EB15 (Trimetazidine)

Active Substance

Trimetazidine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Drug normalizing myocardial metabolism, reducing tissue hypoxia

Pharmacotherapeutic Group

Drugs for the treatment of heart diseases; other drugs for the treatment of heart diseases

Pharmacological Action

A drug that normalizes the energy metabolism of cells exposed to hypoxia or ischemia. It prevents the decrease in intracellular ATP content, ensures the normal functioning of membrane ion channels, transmembrane transfer of potassium and sodium ions, and the preservation of cellular homeostasis.

Trimetazidine slows down the oxidation of fatty acids by selectively inhibiting long-chain 3-ketoacyl-CoA thiolase, which leads to an increase in glucose oxidation and the restoration of coupling between glycolysis and oxidative decarboxylation and has been shown to provide protection of the myocardium from ischemia. The switching of fatty acid oxidation to glucose oxidation underlies the antianginal action of trimetazidine.

Trimetazidine supports the energy metabolism of the heart and neurosensory organs during episodes of ischemia; reduces the degree of intracellular acidosis and the extent of changes in the transmembrane ion flow that occurs during ischemia; reduces the level of migration and infiltration of polymorphonuclear neutrophils in ischemic and reperfused heart tissues, reduces the size of myocardial damage; while it does not affect hemodynamics.

Pharmacokinetics

Trimetazidine is rapidly and almost completely absorbed from the gastrointestinal tract. The volume of distribution (V_d) is 4.8 L/kg. It easily passes through histohematic barriers. Plasma protein binding is about 16%.

The elimination half-life (T_1/2) is 4.5-5 hours. It is excreted by the kidneys, mainly unchanged.

Indications

Long-term therapy of coronary artery disease (CAD): prevention of attacks of stable angina pectoris as part of mono- or combination therapy.

ICD codes

Dosage Regimen

Administer Trimektal^® orally with a glass of water. Take tablets during meals to minimize potential gastrointestinal discomfort.

The recommended therapeutic dose for adults is 40 mg to 70 mg per day. Divide the total daily dose into two or three separate administrations to maintain stable plasma concentrations.

For the 20 mg tablet strength, the typical regimen is one tablet three times daily with meals, equating to a total daily dose of 60 mg. Alternatively, for the 35 mg modified-release tablet strength, the regimen is one tablet twice daily with breakfast and dinner, providing a 70 mg total daily dose.

Adhere strictly to the dosing schedule prescribed by your physician. Do not alter the dose or frequency without medical consultation.

The duration of therapy is determined individually based on the clinical presentation and treatment response. Continue treatment for as long as your physician deems it clinically necessary.

In patients with moderate renal impairment (creatinine clearance 30-60 ml/min), monitor therapy closely. This drug is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 ml/min).

Exercise caution when prescribing to patients over 75 years of age. No specific dose adjustment is routinely required, but individual patient factors should be considered.

If a dose is missed, take it as soon as remembered unless it is nearly time for the next scheduled dose. Do not double the dose to make up for a forgotten one.

This medication is for long-term prophylactic management of stable angina pectoris and is not indicated for aborting acute angina attacks.

Adverse Reactions

From the digestive system: frequently – abdominal pain, diarrhea, dyspepsia, nausea, vomiting; frequency unknown – constipation.

From the nervous system: frequently – dizziness, headache; infrequently – paresthesia; frequency unknown – symptoms of parkinsonism (tremor, akinesia, increased tone), instability in the Romberg position and unsteady gait, restless legs syndrome (usually reversible after discontinuation of therapy), insomnia, drowsiness.

From the hearing organ and labyrinthine disorders: frequency unknown – vertigo.

From the skin and subcutaneous tissues: frequently – skin rash, itching, urticaria; frequency unknown – acute severe skin adverse reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS syndrome) and acute generalized exanthematous pustulosis, which can be fatal.

Allergic reactions: frequency unknown – angioedema.

From the cardiovascular system: rarely – palpitations, extrasystole, tachycardia, marked decrease in blood pressure, orthostatic hypotension (may be accompanied by general weakness, dizziness, or loss of balance, especially when taken simultaneously with antihypertensive drugs), flushing.

From the hematopoietic system: frequency unknown – agranulocytosis, thrombocytopenia, thrombocytopenic purpura.

From the liver and biliary tract: frequency unknown – hepatitis.

Other: frequently – asthenia.

Contraindications

Hypersensitivity to trimetazidine; Parkinson’s disease, symptoms of parkinsonism, tremor, restless legs syndrome and other related movement disorders; severe renal failure (creatinine clearance less than 30 ml/min); children and adolescents under 18 years of age; pregnancy, lactation (breastfeeding).

With caution

Patients with moderate renal failure (creatinine clearance 30-60 ml/min), patients with severe hepatic failure (10 to 15 points on the Child-Pugh scale); patients over 75 years of age.

Use in Pregnancy and Lactation

Trimetazidine is contraindicated for use during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Should be used with caution in patients with severe hepatic impairment (10 to 15 points on the Child-Pugh scale).

Use in Renal Impairment

Contraindicated in severe renal failure (creatinine clearance less than 30 ml/min). Should be used with caution in patients with moderate renal failure (creatinine clearance 30-60 ml/min).

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Should be used with caution in patients over 75 years of age.

Special Precautions

It is not intended for the relief of angina attacks and is not indicated for the initial course of therapy for unstable angina or myocardial infarction at the pre-hospital stage or in the first days of hospitalization.

Effect on the ability to drive vehicles and mechanisms

During the use of trimetazidine, patients should exercise caution when driving vehicles and mechanisms, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.