Antisten SR (Tablets) Instructions for Use

Marketing Authorization Holder

Ozon, LLC (Russia)

Contact Information

Ozon, LLC (Russia)

ATC Code

C01EB15 (Trimetazidine)

Active Substance

Trimetazidine (Rec.INN registered by WHO)

Dosage Form

Antisten SR

Prolonged-release film-coated tablets, 35 mg: 10, 20, 30, 40, 50, 60, 80, 90, 100, 120, 150, 180, 200 or 300 pcs.

Dosage Form, Packaging, and Composition

Prolonged-release film-coated tablets cream-pink in color, biconvex; a cross-section shows two layers, the inner layer (core) is white or white with a yellowish tint.

Excipients: hypromellose – 93 mg, microcrystalline cellulose – 178.9 mg, colloidal silicon dioxide – 1.55 mg, magnesium stearate – 1.55 mg.

Film coating composition: Opadry II 85F240012 Pink (polyvinyl alcohol – 4 mg, macrogol 3350 – 2.438 mg, iron oxide red – 0.04 mg, iron oxide yellow – 0.022 mg, talc – 1.48 mg, titanium dioxide – 2.02 mg).

10 pcs. – contour cell packaging (1) – cardboard boxes.
10 pcs. – contour cell packaging (2) – cardboard boxes.
10 pcs. – contour cell packaging (3) – cardboard boxes.
10 pcs. – contour cell packaging (4) – cardboard boxes.
10 pcs. – contour cell packaging (5) – cardboard boxes.
10 pcs. – contour cell packaging (6) – cardboard boxes.
10 pcs. – contour cell packaging (10) – cardboard packs.
20 pcs. – contour cell packaging (1) – cardboard packs.
20 pcs. – contour cell packaging (2) – cardboard packs.
20 pcs. – contour cell packaging (3) – cardboard packs.
20 pcs. – contour cell packaging (4) – cardboard packs.
20 pcs. – contour cell packaging (5) – cardboard packs.
20 pcs. – contour cell packaging (6) – cardboard packs.
20 pcs. – contour cell packaging (10) – cardboard packs.
30 pcs. – contour cell packaging (1) – cardboard packs.
30 pcs. – contour cell packaging (2) – cardboard packs.
30 pcs. – contour cell packaging (3) – cardboard packs.
30 pcs. – contour cell packaging (4) – cardboard packs.
30 pcs. – contour cell packaging (5) – cardboard packs.
30 pcs. – contour cell packaging (6) – cardboard packs.
30 pcs. – contour cell packaging (10) – cardboard packs.
10 pcs. – polymer containers (1) – cardboard packs.
20 pcs. – polymer containers (1) – cardboard packs.
30 pcs. – polymer containers (1) – cardboard packs.
40 pcs. – polymer containers (1) – cardboard packs.
50 pcs. – polymer containers (1) – cardboard packs.
60 pcs. – polymer containers (1) – cardboard packs.
100 pcs. – polymer containers (1) – cardboard packs.

Clinical-Pharmacological Group

Drug improving metabolism of the myocardium and neurosensory organs under ischemic conditions

Pharmacotherapeutic Group

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

Pharmacological Action

It has an antihypoxic effect. By acting directly on cardiomyocytes and brain neurons, the drug optimizes their metabolism and function. The cytoprotective effect is due to an increase in energy potential, activation of oxidative decarboxylation, and rationalization of oxygen consumption (enhancement of glycolysis and blockade of fatty acid oxidation).

Trimetazidine maintains myocardial contractility, prevents a decrease in intracellular ATP and phosphocreatinine content. Under conditions of acidosis, it normalizes the functioning of membrane ion channels, prevents the accumulation of calcium and sodium ions in cardiomyocytes, and normalizes the intracellular potassium ion content.

It reduces intracellular acidosis and the increased phosphate content caused by myocardial ischemia and reperfusion. It prevents the damaging effect of free radicals, preserves the integrity of cell membranes, prevents neutrophil activation in the ischemic zone, increases the duration of the electrical potential, reduces the release of CPK from cells and the severity of ischemic myocardial damage.

Trimetazidine reduces the frequency of angina attacks, reduces the need for nitrate intake, increases exercise tolerance after 2 weeks of administration, and reduces sharp fluctuations in blood pressure. It reduces dizziness and tinnitus of ischemic etiology. In vascular eye pathology, it restores the functional activity of the retina.

Pharmacokinetics

Absorption and Distribution

After oral administration, Trimetazidine is rapidly and almost completely absorbed from the gastrointestinal tract. Bioavailability is 90%. Time to reach C_max in plasma is 3-5 hours. Steady state is reached after 60 hours. V_d is 4.8 L/kg. Plasma protein binding is 16%. It easily penetrates histohematic barriers.

Elimination

Trimetazidine is eliminated from the body mainly by the kidneys (about 60% unchanged). T_1/2 is about 7 hours.

Pharmacokinetics in Special Clinical Cases

T_1/2 in patients over 65 years old is about 12 hours. Renal clearance of trimetazidine directly correlates with CrCl, hepatic clearance decreases with age.

Indications

• Coronary artery disease: prevention of angina attacks (as part of combination therapy);
• Cochleovestibular disorders of ischemic origin, such as dizziness, tinnitus, hearing impairment;
• Chorioretinal vascular disorders.

ICD codes

Dosage Regimen

Administer Antisten SR orally, with meals.

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

The standard adult dosage is one 35 mg tablet taken twice daily, in the morning and in the evening.

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

This product is not for the initial treatment of unstable angina or myocardial infarction.

Do not use Antisten SR to abort an acute angina attack; it is for prophylactic use only.

If a dose is missed, take the next dose at the regular time; do not double the dose.

In patients over 65 years, the elimination half-life is prolonged; consider this during long-term therapy.

The total duration of treatment is determined individually by the physician based on clinical response.

Regularly reassess the therapeutic regimen for efficacy and tolerability.

Discontinue treatment if symptoms of extrapyramidal disorders, such as tremor or rigidity, occur.

Adverse Reactions

Frequency: very common – more than 1/10; common – more than 1/100 and less than 1/10; uncommon – more than 1/1000 and less than 1/100; rare – more than 1/10000 and less than 1/1000; very rare – less than 1/100000, including isolated reports.

Gastrointestinal system: common – abdominal pain, diarrhea, dyspepsia, nausea, vomiting.

Cardiovascular system: rare – orthostatic hypotension, facial flushing.

CNS: common – dizziness, headache; very rare – extrapyramidal disorders (tremor, rigidity, akinesia), reversible after drug withdrawal.

Dermatological reactions: common – skin rash, itching, urticaria.

Other: common – asthenia.

Contraindications

• Hypersensitivity to any component of the drug;
• Renal failure (CrCl less than 15 ml/min);
• Severe hepatic impairment;
• Age under 18 years (efficacy and safety have not been established).

Use in Pregnancy and Lactation

Animal studies have not revealed a teratogenic effect; however, due to the lack of clinical data on the safety of the drug during pregnancy, the risk of fetal malformations cannot be excluded. Use during pregnancy is contraindicated.

It is unknown whether Antisten SR is excreted in breast milk. If it is necessary to use the drug during lactation, the issue of discontinuing breastfeeding should be considered.

Use in Hepatic Impairment

Contraindication: severe hepatic impairment.

Use in Renal Impairment

Contraindication: renal failure (CrCl less than 15 ml/min).

Pediatric Use

Contraindication: age under 18 years (efficacy and safety have not been established).

Geriatric Use

T_1/2 in patients over 65 years old is about 12 hours.

Special Precautions

Do not use to relieve angina attacks!

The drug is not indicated for the initial course of therapy for unstable angina or myocardial infarction.

In case of an angina attack, treatment should be reviewed and adapted.

If one or more doses are missed, a higher dose should not be taken at the next intake.

Effect on ability to drive vehicles and operate machinery

Antisten SR does not significantly affect the ability to drive vehicles and perform other work requiring high speed of psychomotor reactions.

Overdose

There are currently no reports of drug overdose.

Drug Interactions

There is no information on drug interactions.

Storage Conditions

The drug should be stored in a dry, light-protected place, out of the reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

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.