Trimectal MV tablets 35mg, no. 120

The drug is taken orally, during meals, without chewing, with water.

Assign 1 tab. 2 times / day (morning and evening). The duration of the course of treatment is according to the doctor's recommendation.

In patients with moderate renal insufficiency (CC 30-60 ml / min), the daily dose is 35 mg (in the morning, during breakfast).

In patients older than 75 years may experience increased exposure trimetazidina because age-related decrease in renal function. Dose selection in patients of this group should be done with caution.

Modified release tablets, film-coated, almost white or white with a yellowish sheen, round, biconvex.

1 tab. trimetazidine dihydrochloride 35 mg

Excipients : Kollidon SR (polyvinyl acetate 80%, povidone 19%, sodium lauryl sulfate 0.8%, silicon dioxide 0.2%) - 137.5 mg, calcium hydrogen phosphate dihydrate - 73.8 mg, colloidal silicon dioxide - 1.2 mg, magnesium stearate - 2.5 mg.

The composition of the film shell: (hypromellose - 4.8 mg, talc - 1.6 mg, titanium dioxide - 0.88 mg, macrogol 4000 (polyethylene glycol 4000) - 0.72 mg) or (dry mixture for a film coating containing 60% hypromellose, talc 20%, titanium dioxide 11%, macrogol 4000 (polyethylene glycol 4000) 9%) - 8 mg.

• Parkinson's disease, parkinsonism symptoms, tremors, restless legs syndrome and other associated movement disorders;

• severe renal failure (CC less than 30 ml / min);

• pregnancy;

• lactation period (breastfeeding);

• age up to 18 years (efficacy and safety have not been established);

• hypersensitivity to the components of the drug.

Precautions: severe hepatic impairment (limited clinical data); moderate renal failure (CC 30-60 ml / min); over 75 years of age.

Release form, packaging and composition of the drug TrimectalЃ MV

Modified release tablets, film-coated, almost white or white with a yellowish sheen, round, biconvex.

1 tab. trimetazidine dihydrochloride 35 mg

Excipients : Kollidon SR (polyvinyl acetate 80%, povidone 19%, sodium lauryl sulfate 0.8%, silicon dioxide 0.2%) - 137.5 mg, calcium hydrogen phosphate dihydrate - 73.8 mg, colloidal silicon dioxide - 1.2 mg, magnesium stearate - 2.5 mg.

The composition of the film shell: (hypromellose - 4.8 mg, talc - 1.6 mg, titanium dioxide - 0.88 mg, macrogol 4000 (polyethylene glycol 4000) - 0.72 mg) or (dry mixture for a film coating containing 60% hypromellose, talc 20%, titanium dioxide 11%, macrogol 4000 (polyethylene glycol 4000) 9%) - 8 mg.

Clinical and pharmacological group: A drug that normalizes myocardial metabolism, reduces tissue hypoxia

Pharmaco-therapeutic group: Antihypoxic agent

pharmachologic effect

Trimetazidine has an antihypoxic effect. By directly affecting the cardiomyocytes and neurons of the brain, trimetazidine optimizes their metabolism and function. The cytoprotective effect of trimetazidine is due to an increase in energy potential, activation of oxidative decarboxylation and rationalization of oxygen consumption (increased aerobic glycolysis and blockade of fatty acid oxidation). Trimetazidine inhibits fatty acid oxidation due to the enzyme 3-ketoacyl-CoA-thiolase (3-CAT) of the mitochondrial long-chain fatty acid isoform, which leads to increased glucose oxidation and accelerated glycolysis with glucose oxidation, which is responsible for the protection of the myocardium from ischemia. Switching energy metabolism from fatty acid oxidation to glucose oxidation underlies the pharmacological properties of trimetazidine.

Trimetazidine maintains myocardial contractility, prevents a decrease in the intracellular content of ATP and phosphocreatine.

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 content of potassium ions.

Trimetazidine reduces intracellular acidosis and increased phosphate levels due to myocardial ischemia and reperfusion. It prevents the damaging action of free radicals, preserves the integrity of cell membranes, prevents the activation of neutrophils in the ischemic zone, increases the duration of the electric potential, reduces the release of CPK from cells and the severity of ischemic damage to the myocardium.

Trimetazidine reduces dizziness and tinnitus. In case of vascular pathology of the eye, it improves the functional activity of the retina.

It has been experimentally confirmed that trimetazidine has the following properties:

• supports the energy metabolism of the heart and neurosensory tissues during ischemia;

• supports myocardial contractility, prevents intracellular depletion of adenosine triphosphoric acid and creatine phosphate;

• under conditions of acidosis normalizes the functioning of ion channels of membranes, prevents the accumulation of calcium and sodium ions in cardiomyocytes, normalizes the intracellular concentration of potassium ions;

• reduces the severity of intracellular acidosis and changes in the transmembrane ion flow that occur during ischemia;

• reduces the level of migration and infiltration of polynuclear neutrophils in ischemic and reperfused heart tissues;

• prevents the damaging action of free radicals, preserves the integrity of cell membranes, prevents the activation of neutrophils in the ischemic zone, increases the duration of the electric potential, reduces the release of CPK from cells and the severity of ischemic damage to the myocardium;

• reduces the size of myocardial damage;

• does not directly affect hemodynamic parameters.

In patients with angina pectoris, trimetazidine:

• increases the coronary reserve, thereby slowing the onset of exercise-induced ischemia, starting from the 15th day of therapy;

• limits fluctuations in blood pressure caused by physical activity, without significant changes in heart rate;

• significantly reduces the frequency of angina attacks and the need to take short-acting nitroglycerin;

• improves the contractile function of the left ventricle in patients with ischemic dysfunction.

The results of clinical studies have confirmed the efficacy and safety of using trimetazidine in patients with stable angina pectoris both in monotherapy and as part of complex therapy with an insufficient effect of other antianginal drugs.

Pharmacokinetics

Suction

After taking the drug inside, trimetazidine is rapidly and almost completely absorbed from the gastrointestinal tract. Bioavailability is 90%. Food intake does not affect the bioavailability of trimetazidine. The time to reach Cmax in blood plasma is 5 hours. Over 24 hours, the concentration of trimetazidine in blood plasma remains at a level exceeding 75% of the concentration determined after 11 hours.

Distribution

Plasma protein binding is about 16% in vitro. Vd is 4.8 L / kg, which suggests good diffusion of the distribution of trimetazidine in tissues. Easily penetrates histohematogenous barriers. Css is reached after 60 hours.

Withdrawal

Trimetazidine is excreted from the body mainly in the urine (about 60% - unchanged). T1 / 2 about 7 hours

Pharmacokinetics in special patient groups

Renal clearance of trimetazidine directly correlates with CC, hepatic clearance decreases with age.

The exposure of trimetazidine was on average increased 2.4 times in patients with moderate renal insufficiency (CC 30-60 ml / min), and on average 4 times in patients with severe renal insufficiency (CC less than 30 ml / min) compared with healthy volunteers with normal renal function. No safety features were found in this patient population compared to the general population.

In patients over the age of 65, T1 / 2 is about 12 hours. In patients over 75, an increased exposure of trimetazidine may be observed due to age-related decline in renal function. No safety features were found in patients over 75 years of age compared to the general population.

Indications of the drug TrimectalЃ MB

IHD: prevention of attacks of stable angina pectoris (as part of mono- or combination therapy).

Dosage regimen

The drug is taken orally, during meals, without chewing, with water.

Assign 1 tab. 2 times / day (morning and evening). The duration of the course of treatment is according to the doctor's recommendation.

In patients with moderate renal insufficiency (CC 30-60 ml / min), the daily dose is 35 mg (in the morning, during breakfast).

In patients older than 75 years may experience increased exposure trimetazidina because age-related decrease in renal function. Dose selection in patients of this group should be done with caution.

Side effect

Classification of the incidence of side effects according to the WHO recommendations: very often (? 1/10); often (from? 1/100 to <1/10); infrequently (from? 1/1000 to <1/100); rarely (from? 1/10 000 to <1/1000); very rarely <1/10 000, including isolated reports); the frequency is unknown (according to available data, it is not possible to establish the frequency of occurrence).

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

From the nervous system: often - dizziness, headache; the frequency is unknown - symptoms of parkinsonism (tremor, akinesia, increased tone), instability in the Romberg position and unsteadiness of gait, restless legs syndrome, other associated movement disorders, usually reversible after discontinuation of therapy; sleep disorders (insomnia, drowsiness).

From the side of the cardiovascular system: rarely - a feeling of palpitations, extrasystole, tachycardia, a marked decrease in blood pressure, orthostatic hypotension, which may be accompanied by general weakness, dizziness or loss of balance, especially while taking antihypertensive drugs, 'hot flushes' of blood to the skin of the face.

From the digestive system: often - abdominal pain, diarrhea, dyspepsia, nausea, vomiting; frequency unknown - constipation, hepatitis.

On the part of the skin: often - skin rash, itching.

Allergic reactions: often - urticaria; frequency unknown - Quincke's edema, acute generalized exanthematous pustulosis.

Others: often - asthenia.

Contraindications for use

• Parkinson's disease, parkinsonism symptoms, tremors, restless legs syndrome and other associated movement disorders;

• severe renal failure (CC less than 30 ml / min);

• pregnancy;

• lactation period (breastfeeding);

• age up to 18 years (efficacy and safety have not been established);

• hypersensitivity to the components of the drug.

Precautions: severe hepatic impairment (limited clinical data); moderate renal failure (CC 30-60 ml / min); over 75 years of age.

Application during pregnancy and lactation

There are no data on the use of trimetazidine in pregnant women. Animal studies have shown no direct or indirect reproductive toxicity. Reproductive toxicity studies did not show the effect of trimetazidine on the reproductive function of rats of both sexes. As a precautionary measure, it is not recommended to use TrimectalЃ MB during pregnancy.

There are no data on the excretion of trimetazidine or its metabolites in breast milk. The risk to the newborn / child cannot be excluded. You should not use the drug TrimectalЃ MB during breastfeeding.

Application for violations of liver function

The drug should be prescribed with caution to patients with severe hepatic impairment.

Application for impaired renal function

The drug is contraindicated in severe renal failure (CC less than 30 ml / min).

With caution should be given to patients with renal drug moderate impairment (creatinine clearance of 30-60 ml / min), it is necessary to reduce the dosing frequency to 1 times / day (in the morning, during lunch time).

Application in children

Contraindicated in children and adolescents under 18 years of age (efficacy and safety have not been established).

Use in elderly patients

The drug should be prescribed with caution to elderly patients (over 75 years old).

In elderly patients, it is necessary to reduce the frequency of admission to 1 time / day (in the morning, during breakfast).

special instructions

If you miss one or more doses of TrimectalЃ MB, you should not take a higher dose in the next dose.

TrimectalЃ MV is not intended for relieving angina attacks and is not indicated for the initial course of therapy for unstable angina pectoris or myocardial infarction at the prehospital stage or in the first days of hospitalization.

In the event of an attack of angina pectoris, the treatment (drug therapy or revascularization procedure) should be reviewed and adapted.

Trimetazidine can cause or worsen the symptoms of parkinsonism (tremor, akinesia, increased tone), therefore, patients should be regularly monitored, especially the elderly. In cases of doubt, patients should be referred to a neurologist for appropriate examination. If movement disorders appear, such as parkinsonism symptoms, restless legs syndrome, tremors, unsteadiness in the Romberg position and unsteadiness of gait, trimetazidine should be finally canceled. Such cases are rare, and symptoms usually disappear after discontinuation of therapy: in most patients, within 4 months after discontinuation of the drug. If the symptoms of parkinsonism persist for more than 4 months after discontinuation of the drug, a neurologist should be consulted. Falls may occur,associated with instability in the Romberg position and unsteadiness of gait or a pronounced decrease in blood pressure, especially in patients taking antihypertensive drugs.

Care should be taken to prescribe the drug TrimectalЃ MB to patients who may have increased exposure to trimetazidine (patients with moderate renal insufficiency (CC 30-60 ml / min), as well as elderly patients over 75 years old).

Due to the peculiarities of the dosage form of the drug TrimectalЃ MV, modified-release film-coated tablets, the tablet framework of the drug may not dissolve in the intestine and be excreted in the feces, which does not affect the therapeutic efficacy of the drug.

Influence on the ability to drive vehicles and use mechanisms

Given the possibility of the development of adverse reactions from the central nervous system when taking trimetazidine, care should be taken when driving vehicles and other technical devices that require increased concentration of attention and speed of psychomotor reactions.

Overdose

Currently, no cases of drug overdose have been reported.

Treatment: in case of overdose, symptomatic therapy should be carried out.

Drug interactions

Trimetazidine can be used simultaneously with heparin, calciparin, indirect anticoagulants, drugs used for lipid metabolism disorders, salicylic acid, beta-blockers, slow calcium channel blockers, cardiac glycosides.

In clinical trials, trimetazidine has been shown to increase the anti-ischemic activity of other antianginal drugs.

No other interaction was observed.

Storage conditions of the drug Trimectal MB

The drug should be stored out of the reach of children, protected from light at a temperature not exceeding 25 ? C.

Shelf life of the drug TrimectalЃ MB

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

Terms of sale

The drug is available with a prescription.