Trimetazidine - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate - 127.70 mg; corn starch - 0.80 mg; povidone (low-molecular weight butylvinylpyrrolidone) 0.80 mg; calcium stearate -0.70 mg;

capsules, hard gelatinous: body (titanium dioxide - 2%, gelatin - up to 100%); lid (titanium dioxide - 1%, iron oxide yellow (iron oxide) - 1,7143%, indigocarmine -0.3%, gelatin - up to 100%).

Description:

Hard gelatin capsules No. 3 with a white body, a lid of green color. The contents of the capsules are a powder or compacted mass of white or almost white color, disintegrating when pressed.

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 antihypoxic effect. By directly affecting cardiomyocytes and neurons of the brain, trimetaside optimizes their metabolism and function. The cytoprotective effect of trimetazidine is due to an increase energy potential, activation of oxidative decarboxylation and rationalization of oxygen consumption (enhancement of aerobic glycolysis and blockade of fatty acid oxidation). Trimetaside inhibits the oxidation of fatty acids by the enzyme 3-ketoacyl-CoA-thiolase (3-CAT) of the mitochondrial long chain isoform of fatty acids, which leads to increased glucose oxidation and acceleration of the glycosylation of glucose senescence, which determines myocardial protection from ischemia.Switching energy metabolism from the oxidation of fatty acids to the oxidation of glucose underlies the pharmacological properties of trimetazidine.

Trimetazidine supports myocardial contractility, prevents

intracellular content of adenosine triphosphate (ATP) and phosphocreatine.

Under acidosis, it normalizes the functioning of ion channels of membranes, prevents the accumulation of calcium and sodium ions in cardiomyocytes, normalizes intracellular retention of potassium ions.

Trimetazidine reduces intracellular acidosis and elevated phosphate content, aboutagreed by 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 (CK) from cells and the severity of ischemic myocardial damage. Trimetazidine reduces dizziness and tinnitus. In vascular pathology, the eye improves the functional activity of the retina. It is experimentally confirmed that trimetazidine 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;

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

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

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

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

Pharmacokinetics:

Suction

After oral administration trimetazidine fast and practicalcompletely absorbedgastrointestinal tract. Biostudunism - 90 %.

The time to reach the maximum concentration in the blood plasma is 2 hours (the maximum concentration after a single dose of 20 mg trimetazidine at about 55 ng / ml).

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. Easily penetrates through the histohematological barriers.

Excretion

Trimetazidine is excreted from the body mainly by the kidneys (about 60% - unchanged). The half-life is about 4.5-5 hours.

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

Pharmacokinetics in specific patient groups

Patients with impaired renal function

Exposure of trimetazidine on average was increased by 2.4 times in patients with moderate-grade renal adequacy (QC 30-60 ml / min),and an average of 4 times - patients with renal insufficiency of severe severity (QC less than 30 ml / min) compared with healthy volunteers with normal renal function, which features of safety in this population of patients in comparison with the population of the population was not found.

Paelderly people

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);

- Pregnancy;

- the period of breastfeeding;

- increase to 18 years (efficiency and safety not established);

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Carefully:

Renal insufficiency of moderate severity (CK 30-60 ml / min); hepatic failure of severe severity (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 the drug Trimetazidine during pregnancy.

Breastfeeding period

Data on the release of trimetazidine or its metabolites in breast milk are not available. Risk for a newborn / child can not be excluded. Do not use the drug Trimetazidine during breastfeeding.

Dosing and Administration:

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

A drug Trimetazidine appoint 1 capsule 3 times a day.

The duration of the course of treatment is according to the doctor's recommendation.

Special patient groups

Patients with impaired renal function

In patients with moderate-grade renal failure (CK 30-60 mL / min), the recommended dose is 20 mg twice daily (morning and evening) with meals.

Elderly patients

In patients older than 75 years, there may be an increased exposure of trimetazidine due to age-related decline in renal 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 incidence of adverse events according to the recommendations of the World Health Organization Health Organization (WHO):

very often> 1/10;

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

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

rarely from> 1/10000 to <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.

Co side of the digestive system:

chaone hundred - abdominal pain, diarrhea, dyspepsia, nausea, vomiting;

frequency unknown - constipation.

General disorders: often - asthenia.

Co side of the central nervous system:

often - dizziness, headache;

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

Co 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 is 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 trials of trimetazidine, it has been shown that it promotes an increase in the antisemic activity of other antianginal drugs.

No other interactions were observed.

Special instructions:

A drug Trimetazidine 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 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 whiter 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 necessary to prescribe the drug Trimetazidine patients who may increase its exposure: patients with moderate-grade renal failure (QC 30-60 ml / min), as well as elderly patients over 75 years of age.

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

Given 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 that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Capsules 20 mg.

Packaging:

10 or 20 capsules in a planar cell packaging made of polyvinylchloride film and aluminum foil.

60 capsules in a jar of high-density polyethylene.

3 or 5 contour cell packs but 20 capsules, 3 or 6 contiguous 10-capsule cell packs, or one pot together with instructions for use in a pack of cardboard.

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 expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000013

Date of registration:19.02.2010

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

Trimetazidine (Trimetazidine)