Trimetazidine MB - instructions for use, dose, side effects, contraindications

Excipients: calcium hydrophosphate anhydrous - 157.0 mg; hypromellose - 50.0 mg; silicon dioxide colloidal - 2.0 mg; crospovidone - 2.5 mg; talc - 2.0 mg; magnesium stearate - 1.5 mg.

Composition of the tablet shell: fall off II pink (85F34610) - 8.0 mg (polyvinyl alcohol 40.00%, titanium dioxide 24.24%, macrogol 3350-20.20%, talc 14.80%, iron dye oxide yellow 0.37%, dye iron oxide red - 0.36%, ferric oxide black oxide - 0.03%).

Description:Tabsites of round, biconvex form, covered with a film membrane from pink to brownish-pink, with a risk on one side. On the transverse section - the core is from white or almost white to white with a yellowish tint of color.

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:

Has antihypoxic effect.

Directly affecting the cardiomyocytes and neurons of the brain, it optimizes their metabolism and function. The cytoprotective effect is caused by an increase in the energy potential, activation of oxidative decarboxylation, and rationalization of oxygen consumption (enhancement of aerobic glycolysis and blockade of oxidation of fatty acids by inhibition of long chain3-ketoacyl-CoA thiolase).

It is experimentally confirmed that trimetazidine has the following properties:

- maintains myocardial contractility, prevents intracellular depletion of adenosine triphosphate and creatine phosphate;

- in the 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 intracellular acidosis and increased 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 ischemia zone, prolongs the duration of the electrical potential, reduces the yield of creatine phosphokinase from cells and the severity of myocardial ischemic damage;

- does not directly affect the parameters of hemodynamics.

In patients with angina pectoris, trimetazidine:

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

- limits blood pressure fluctuations caused by physical exertion, without significant changes in heart rate;

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

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

Pharmacokinetics:

Suction:

After oral administration trimetazidine quickly and almost completely absorbed in the gastrointestinal tract. Bioavailability is 90%. The time to reach the maximum concentration in the blood plasma is about 5 hours. Over 24 hours, the concentration of trimetazidine in the blood plasma is maintained at a level greater than and equal to 75% of the maximum concentration determined within 11 hours. Equilibrium concentration with regular admission is achieved after 60 hours. Simultaneous reception food does not affect the bioavailability of trimetazidine.

Distribution:

The volume of distribution is 4.8 l / kg. The degree of binding to blood plasma proteins is quite low - about 16% in vitro.

Excretion:

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

The clearance of trimetazidine is characterized by a greater degree of renal clearance, which is directly correlated with the clearance of creatinine (CC), and to a lesser extent - with hepatic clearance, which decreases with the age of the patient.

Special Groups

Patients older than 75 years

In patients older than 75 years, there may be an increase in the concentration of trimetazidine in the blood plasma because of the age-related decline in kidney function. A special study was conducted in a population of patients older than 75 years with the administration of 35 mg of trimetazidine tablets twice a day. Analysis, carried out by the kinetic population method, showed an average double increase in plasma concentration in patients with renal insufficiency of severe degree (QC less than 30 ml / min) compared with patients with SC greater than 60 ml / min.

There were no safety features in patients older than 75 years compared with the general population.

Patients with renal insufficiency

The concentration of trimetazidine in blood plasma was increased by an average of 2.4 times in patients with moderate renal insufficiencythe degree of severity (CK 30-60 ml / min) and an average of 4 times - in patients with severe renal insufficiency (KC 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.

Application in children and adolescents

The pharmacokinetics of trimetazidine in children and adolescents under the age of 18 years have not been studied.

Indications:

Long-term therapy of ischemic heart disease: prevention of attacks of stable angina in the mono-or combination therapy.

Contraindications:

- Hypersensitivity to any of the components of the drug;

- Parkinson's disease, Parkinson's symptoms, tremor, restless legs syndrome;

- severe renal failure (CC less than 30 ml / min).

Due to the lack of sufficient clinical data for patients under 18 years of age, the use of the drug is not recommended.

Carefully:

- Patients with mild renal insufficiency (KK 30-60 ml / min);

- patients older than 75 years.

Pregnancy and lactation:

Data on the use of the drug Trimetazidine MB in pregnant women are absent.Studies in animals have not revealed a presence of direct or indirect reproductive toxicity. Reproductive toxicity studies did not show the effect of trimetazidine on reproductive function in rats of both sexes. As a precaution, it is not recommended to use the drug Trimetazidine MB during pregnancy.

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 the drug Trimetazidine MV during breastfeeding.

Dosing and Administration:

Tablets should be taken whole, not liquid, squeezed with water.

Inside, 1 tablet 2 times a day, morning and evening, with meals. The duration of treatment is determined by the doctor.

The maximum daily dose is 70 mg.

Special Groups

Patients with renal insufficiency

In patients with moderate-grade renal failure (CK 30-60 ml / min) daily dose is 35 mg (1 tablet), in the morning during breakfast.

Patients older than 75 years

In patients older than 75 years, an elevated concentration of trimetazidine in the blood plasma may be observed due to the age-related decline in kidney function (see Fig.section "Pharmacokinetics"). In patients with moderate-grade renal failure (CK 30-60 ml / min), the recommended daily dose is 35 mg (1 tablet), in the morning during breakfast. The choice of dose in patients older than 75 years should be done with caution (see section "Special instructions").

Side effects:

Undesirable reactions, defined as undesirable events, at least with possible relevance to treatment with trimetazidine, are given in the following gradation: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rarely (<1/10000); frequency (frequency can not be calculated from available data).

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

From the central nervous system: often - dizziness, headache; Unspecified frequency - Parkinsonism symptoms (tremor, akinesia, tone increase); instability in the Romberg position and the "unsteadiness" of the gait; syndrome of "restless legs" and other disorders associated with the musculoskeletal system, usually reversible after discontinuation of therapy; sleep disorders (insomnia, drowsiness).

From the skin: often - skin rash, itching, hives; unspecified frequency - acute generalized exanthematous pustulosis.

Allergic reactions: frequency of unspecified - Quincke's edema.

From the side of the cardiovascular system: rarely - palpitation, 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: Unspecified frequency - agranulocytosis, thrombocytopenia, thrombocytopenic purpura.

Other: often - asthenia.

Overdose:

There is only limited information about an overdose of trimetazidine. In case of an overdose, symptomatic therapy should be given.

Interaction:

Not observed.

Special instructions:

Trimetazidine MB is not intended for relief of 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 angina attack, treatment should be reviewed and adapted (drug therapy or revascularization procedure).

Trimetazidine MB can 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.

When motor disorders such as Parkinsonism symptoms, restless legs syndrome, tremor, Romberg pose instability and gait unsteadiness occur, Trimetazidine MB should be finally abolished.

Such cases are rare and symptoms usually pass 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 a pronounced decrease in blood pressure, especially in patients taking antihypertensive drugs (see the "Side effect" section).

Caution should be used to administer Trimetazidine MV to patients who may have an increase in trimetazidine in the blood plasma:

- PIn the case of moderate renal insufficiency (see the sections "Pharmacological properties" and "Method of administration and dose");

- the elderly patients older than 75 years (see section "Method of administration and dose").

Form release / dosage:

Tablets with modified release, film-coated, 35 mg.

Packaging:

For 10 tablets in a contour mesh box made of PVC film and aluminum foil printed lacquered.

By 1, 3, 6, 12 or 18 contour mesh packages together with the instruction for medical use are placed in a cardboard pack.

Storage conditions:

Store in a dark place at a temperature of no higher than 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:LP-003579

Date of registration:20.04.2016

Expiration Date:20.04.2021

The owner of the registration certificate:IZVARINO PHARMA, LLC IZVARINO PHARMA, LLC Russia

Manufacturer: & nbsp

IZVARINO PHARMA, LLC Russia

Representation: & nbspIZVARIN PHARMA LLC IZVARIN PHARMA LLC Russia

Information update date: & nbsp01.07.2016

Illustrated instructions

Instructions

Trimetazidine MB (Trimetazidine MR)