Trimectal MV - instructions for use, dose, side effects, contraindications

Excipients: kollidone SR (80% non-vinyl acetate, 19% povidone, 0.8% sodium lauryl sulfate, 0.2% silica 0.2%) - 137.5 mg; calcium hydrophosphate dihydrate - 73,8 mg; silicon dioxide colloidal - 1.2 mg; magnesium stearate - 2.5 mg;

film sheath: [hypromellose - 4.80 mg, talc - 1.60 mg, titanium dioxide - 0.88 mg, macrogel 4000 (polyethylene glycol 4000) - 0.72 mg] or [dry mixture for film coating containing hypromellose (60%), talc (20%), titanium dioxide (11%), macrogol 4000 (polyethylene glycol 4000) (9%)] - 8.0 mg.

Description:

The tablets covered with a film membrane, almost white or white with a yellowish shade of color, round, biconcave.

Pharmacotherapeutic group:antihypoxic agent

ATX: & nbsp

C.01.E.B Other drugs for the treatment of heart disease

C.01.E.B.15 Trimetazidine

Pharmacodynamics:Trimetazidine has an antihypoxanthio effect. Directly affecting the cardiomyocytes and neurons of the brain, trimetazidine optimizes their metabolism and function. The cytoprotective effect of trimetazidip is due to an increase in the energy potential, activation of oxidative decarboxylation, and rationalization of oxygen consumption (increased aerobic glycolysis and fatty acid oxidation blockade). Trimetazidine inhibits the oxidation of fatty acids due to the enzyme 3-ketoacyl-CoA-thiolase (3-CAT) of the mitochondrial long chain isoform of fatty acids,which leads to increased oxidation of glucose and acceleration of glycolysis with glucose oxidation, which determines the protection of the myocardium from ischemia.

Switching energy metabolism from the oxidation of fatty acids to glucose oxidation underlies the pharmacological properties of trimetazidine. Trimetazidine maintains myocardial contractility, prevents the reduction of intracellular content of adenosine triphosphate (ATP) and phosphocreatine.

In conditions of acidosis normalizes the functioning of ion channels of membranes, prevents the accumulation of calcium and sodium ions in cardiomyocytes, normalizes the intracellular content of potassium ions.

Trimetasidium reduces intracellular acidosis and elevated phosphate content due to myocardial ischemia and reperfusion. Prevents the damaging effect of free radicals, preserves the integrity of cell membranes, prevents the activation of neutrophils in the ischemic zone, prolongs the duration of the electrical potential, reduces the yield of creatine phosphokinase (CK) from cells and the severity of myocardial ischemic damage.

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

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

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

- reduces the intensity of intracellular acidosis and changes in the transmembrane ion flow that occur with ischemia;

- reduces the level of migration and infiltration of polynucleated neutrophils in ischemic and reperfused heart tissues;

- reduces the size of myocardial damage;

- ne has a direct effect on the parameters of hemodynamics.

In patients with angina pectoris:

- increases the coronary reserve, thereby slowing the onset of ischemia caused by physical exertion, starting from the 15th day of therapy;

- Limits fluctuations in blood pressure (BP) caused by physical activity, without significant changes in heart rate;

- significantly reduces the frequency of angina attacks and the need for short-acting nitroglycerin;

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

RezuThe results of clinical trials have confirmed the efficacy and safety of trimetazidine in patients with stable angina in both monotherapy and as part of complex therapy with insufficient effect of other antianginal drugs.

Pharmacokinetics:

Suction

After oral administration trimetazidii quickly and almost completely absorbed in the gastrointestinal tract. Bioavailability is 90%.

Bioavailability reaching the maximum concentration in blood plasma - 5 h.

Over 24 hours, the concentration of trimetazidine in the blood plasma remains at a level exceeding 75% of the concentration, determined after 11 hours.

The equilibrium state is reached after 60 hours.

Eating does not affect the bioavailability of trimetazidine.

Distribution

The volume of distribution is 4.8 l / kg, which implies good diffusion of trimetazidine distribution in tissues. Link with blood plasma proteins about 16% in vitro.

Excretion

Trimetazidine is excreted from the body mainly by the kidneys (about 60% - in unchanged form). Half-life of about 7 hours, in patients older than 65 years - about 12 hours.

Renal clearance of trimetazidine directly correlates with creatinine clearance (CC), the hepatic clearance decreases with the age of the patient.

Easily penetrates through the histohematological barriers.

Pharmacokinetics in special groups patients

Patients with impaired renal function

trimetazidine Exposure was increased by an average 2.4-fold in patients with moderate renal impairment (creatinine clearance of 30-60 ml / min) and an average of 4-fold - in patients with severe renal impairment (creatinine clearance less than 30 mL / min ) compared with healthy volunteers with normal renal function.

No safety features were found in this patient population in comparison with the general population.

Elderly patients

In patients older than 75 years, there may be an increased exposure of trimetazidine due to age-related decline in kidney function.

Indications:

Coronary heart disease: prevention of attacks of stable angina (as part of mono- or combination therapy).

Contraindications:

- Hypersensitivity to any of the components of the drug;

- Parkinson's disease, symptoms of parkinsonism, tremor, restless legs syndrome and other associated motor disorders;

- renal failure of severe severity (QC less than 30 ml / min);

- age to 18 years (efficiency and safety ns established).

Carefully:

- bymoderate insufficiency of moderate severity (CK 30-60 ml / min);

- hepaticsevere complications (clinical data are limited);

- age over 75 years.

Pregnancy and lactation:

Pregnancy

There are no data on the use of trimetazidine in pregnant women. Studies in animals have not revealed the presence of direct or indirect reproductive toxicity. Studies of reproductive toxicity have shown no effect of trimetazidine on the reproductive function of rats of both sexes. As a precaution, do not use Trimectal® CF during pregnancy.

Breastfeeding period

Data on the release of trimetazidine or its metabolites in breast milk are not available. The risk to a newborn / child can not be ruled out. Do not use Trimectal® CF during breastfeeding.

Dosing and Administration:

Inside, during a meal, without chewing, washing with water.

Trimectal® MB appoint 1 tablet 2 times a day (morning and evening).

Aboutduration of treatment - on the recommendation of a doctor.

The maximum daily dose is 70 mg.

Special patient groups

Patients with impaired renal function

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

Elderly patients

Y npatients older than 75 years may experience increased exposure to trimetazidine because of the age-related decline in kidney function (see section "Pharmacokinetics").

The choice of dose in patients older than 75 years should be done with caution (see section "Special instructions").

Side effects:

Classification of the incidence of side effects according to the recommendations of the World Health Organization (WHO);

very often> 1/10;

often from> 1/100 to <1/10;

notoften from> 1/1000 to <1/100;

rarely > 1/10000 before < 1/1000;

very rarely <1/10000, including individual messages;

the frequency is unknown - it is not possible to establish the frequency of occurrence from the available data.

From the digestive system:

often - abdominal pain, diarrhea, dyspepsia, nausea, vomiting;

frequency unknown - constipation.

General disorders:

often - asthenia.

From the central nervous system:

often - dizziness, headache;

frequency unknown - symptoms of parkinsonism (tremor, akinesia,increased tonus), instability in the Romberg position and the "unsteadiness" of the gait, restless legs syndrome, and other associated motor disorders, usually reversible after discontinuation of therapy; sleep disorders (insomnia, drowsiness).

From the skin:

often - skin rash, itching, hives;

frequency unknown - acute generalized exanthematous pustulosis, angioedema.

From the cardiovascular system:

rarely - palpitations, extrasystole, tachycardia, marked decrease in blood pressure, orthostatic hypotension, which can be accompanied by general weakness, dizziness or loss of balance, especially with the simultaneous use of antihypertensive drugs, "tides" of blood to the skin of the face.

From the hematopoiesis:

frequency unknown - agranulocytosis, thrombocytopenia, thrombocytopenic purpura.

From the liver and bile ducts:

frequency is unknown - hepatitis.

Overdose:

At present, no cases of drug overdose have been reported.

In case of an overdose, symptomatic therapy should be given.

Interaction:

In clinical studies of trimetazidine,that it promotes an increase in the anti-ischemic activity of other antianginal drugs.

No other interactions were observed.

Special instructions:

Trimectal ® MB is not intended to stop angina attacks and is not indicated for the initial course of therapy for unstable angina or myocardial infarction at the prehospital stage or in the first days of hospitalization.

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

Trimetazidine may cause or worsen symptoms of parkinsonism (tremor, akinesia, tone increase), therefore, regular monitoring of patients, especially of the elderly, should be carried out. In doubtful cases, patients should be referred to a neurologist for an appropriate examination. With the appearance of motor disorders such as Parkinson's symptoms, restless legs syndrome, tremor, instability in Romberg's pose and the "unsteadiness" of the gait, trimetazidine should be permanently canceled. Such cases are rare, and symptoms usually go away 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, you should consult a neurologist. There may be cases of falls associated with instability in the Romberg position and the "shakiness" of the gait or pronounced decrease in blood pressure, especially in patients taking antihypertensive drugs.

Caution is advised to use Trimectal® MV to patients who can increase its exposure: patients with moderate-grade renal failure (CK 30-60 ml / min), as well as elderly patients older than 75 years.

In view of the medicinal form of the preparation Trimectal® MV modified-release tablets coated with a film coat, the tablet of the drug preparation may not dissolve in the intestine and stand out with feces, which does not affect the therapeutic effectiveness of the drug.

Effect on the ability to drive transp. cf. and fur:

Considering the possibility of developing unwanted reactions from the central nervous system with the administration of trimetazidine (see section "Side effect"), care should be taken when driving vehicles and other technical devices,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Tablets with modified release, film-coated, 35 mg.

Packaging:

10, 20 or 30 tablets in a contour cell box made of a polyvinylchloride film and aluminum foil. 60 tablets in a bike made of high-density polyethylene.

3 or 6 contour cell packs of 10 tablets, 2, 3, 5 or 6 contour packs of 20 tablets, 1, 2 or 4 contourcell packs but 30 tablets or one pot together with instructions for use in a pack of cardboard.

Storage conditions:

Store in a dark place at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-004842/10

Date of registration:27.05.2010

The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia

Manufacturer: & nbsp

VERTEKS, AO Russia

Information update date: & nbsp25.10.2015

Illustrated instructions

Instructions

Trimectal® MB (Trimektal MR)