Preduktal^® MR (Tablets) Instructions for Use

Marketing Authorization Holder

Les Laboratoires Servier (France)

Manufactured By

Les Laboratoires Servier Industrie (France)

Or

Servier Rus, LLC (Russia)

ATC Code

C01EB15 (Trimetazidine)

Active Substance

Trimetazidine (Rec.INN registered by WHO)

Dosage Form

Preduktal® MR

Modified-release tablets, film-coated, 35 mg: 60 pcs.

Dosage Form, Packaging, and Composition

Modified-release tablets, film-coated pink, round, biconvex.

Excipients: calcium hydrogen phosphate dihydrate, hypromellose 4000, magnesium stearate, povidone, colloidal anhydrous silica; dry premix for pink coating: glycerol, macrogol 6000, magnesium stearate, hypromellose, red iron oxide dye (E172), titanium dioxide (E171); polishing: macrogol 6000.

30 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

Antianginal drug

Pharmacotherapeutic Group

Cardiological drugs. Other cardiological drugs. Trimetazidine

Pharmacological Action

An agent that normalizes the energy metabolism of cells subjected to hypoxia or ischemia. It prevents the decrease in intracellular ATP content, ensures the normal functioning of membrane ion channels, transmembrane transport 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 increased glucose oxidation and restoration of the 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. V_d is 4.8 L/kg. It easily passes through histohematic barriers. Plasma protein binding is about 16%.

T_1/2 is 4.5-5 hours. It is excreted by the kidneys, mainly unchanged.

Indications

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

ICD codes

Dosage Regimen

Administer orally with a glass of water during meals.

Swallow the modified-release tablet whole; do not crush, split, or chew.

The standard daily dose is one 35 mg tablet twice daily, equivalent to 70 mg/day.

For specific patient populations, a reduced dose of one 35 mg tablet once daily (35 mg/day) may be utilized.

Adhere strictly to a twice-daily dosing schedule to maintain consistent plasma concentrations.

The duration of therapy is indefinite and determined individually based on the clinical course of coronary artery disease.

Regularly reassess the need for continued antianginal therapy.

Discontinue treatment if symptoms of movement disorders such as parkinsonism, tremor, or restless legs syndrome occur.

Adverse Reactions

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

From the nervous system: common – dizziness, headache; uncommon – paresthesia; frequency unknown – parkinsonian symptoms (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 ear and labyrinth disorders: frequency unknown – vertigo.

From the skin and subcutaneous tissues: common – skin rash, itching, urticaria; frequency unknown – acute severe cutaneous 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: rare – 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: common – asthenia.

Contraindications

Hypersensitivity to trimetazidine; Parkinson’s disease, parkinsonian symptoms, 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 impairment (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 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

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.