Trimetazidine-Teva, 20 mg 60 pcs

Pharmacotherapeutic group: antihypoxant.

ATX code: C01EB15

Pharmacological properties.

Pharmacodynamics

Trimetazidine prevents intracellular reduction of adenosine triphosphatase (ATP) activity under conditions of ischemia and hypoxia, preserving energy metabolism and ensuring cell homeostasis by ensuring normal functioning of cell membrane ion channels and transmembrane sodium-potassium flow. It inhibits beta-oxidation of fatty acids by selectively blocking the enzyme 3-ketoacyl CoA-thiolase, which enhances glucose oxidation. Cells in ischemia require less oxygen for energy during glucose oxidation than during beta-oxidation of fatty acids.

The switch of cellular energy metabolism from fatty acid oxidation to glucose oxidation is the basis of the pharmacological effects of trimetazidine. Under experimental conditions it has been shown that the drug:

– maintains energy metabolism of the heart and neurosensory tissues under conditions of ischemia;

– reduces the severity of intracellular acidosis and changes in transmembrane ion flow occurring during ischemia;

– decreases migration and infiltration of polynuclear neutrophils in ischemic and reperfused heart tissues;

– reduces the size of myocardial damage;

In patients with ischemic heart disease, trimetazidine acts as a metabolic agent, maintaining sufficient intracellular high-energy phosphate activity in the myocardium. The anti-ischemic effect is achieved without affecting hemodynamics.

In patients with stenocardia trimetazidine:

-increases coronary reserve, thereby delaying the onset of exercise-induced ischemia beginning on day 15 of therapy;

-limits exercise-induced blood pressure fluctuations without significant changes in heart rate;

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

– improves left ventricular contractile function in patients with ischemic dysfunction.

Pharmacokinetics

Trimetazidine is rapidly absorbed from the gastrointestinal tract when taken orally, with a maximum plasma concentration (C_max) is reached in less than 2 hours and is 55 ng/ml after a single dose of 20 mg. With repeated use, the equilibrium state of drug concentration in blood is reached after 24-36 hours and remains stable until the end of the course of therapy.

It easily passes through the histohematic barriers. Binding with blood plasma proteins is low (about 16% in vitro).

Extracted from the body mainly by the kidneys (60%) unchanged. The half-life (T_1/2) is 5-6 hours. Total renal clearance of trimetazidine correlates with creatinine clearance (CK), hepatic clearance decreases with age.

Patients over 75 years

In patients over 75 years, an increase in plasma exposure to trimetazidine may be observed due to age-related decrease in renal function. No differences have been found regarding the safety of the drug in patients over 75 years of age compared to the general population.

Patients with impaired renal function

Plasma exposure to trimetazidine was on average 2.4-fold increased in patients with moderate renal impairment (CKR 30-60 ml/min) and on average 4-fold increased in patients with severe renal impairment (CKR less than 30 ml/min) compared with healthy volunteers with normal renal function.

No differences were found regarding the safety of the drug in patients with impaired renal function compared to the general population.

Application in children and adolescents

Pharmacokinetics of trimetazidine in children and adolescents less than 18 years have not been studied.

Indications

Active ingredient

Composition

How to take, the dosage

Overly, 1 tablet 2 to 3 times daily with a meal.

The tablets should be taken whole, without chewing, with water.

The daily dose is 40-60 mg.

The duration of therapy is determined individually, depending on the clinical situation.

Patients with moderate renal dysfunction (CKR 30-60 ml/min)

The recommended dose is 20 mg (1 tablet) 2 times daily (morning and evening).

Patients over 75 years

Patients over 75 years of age may have increased exposure to trimetazidine due to age-related decline in renal function. In patients with moderate renal impairment (CKD 30-60 ml/min), the recommended dose is 20 mg (1 tablet) twice daily (morning and evening). Dosage should be adjusted with caution in patients over 75 years of age (see section “Cautions”).

Interaction

Special Instructions

Trimetazidine is not intended to control angina attacks and is not indicated for initial therapy of unstable angina or myocardial infarction in the pre-hospital phase and the first days of hospitalization.

If an angina attack develops, treatment (drug therapy and possibly revascularization) should be reviewed and adapted.

Trimetazidine may cause or worsen symptoms of parkinsonism (tremor, akinesia, increased muscle tone), so regular monitoring of patients, especially elderly patients, should be performed. If there are any suspicious cases, patients should be advised by a neurologist.

If other movement disorders occur, such as wobbly gait or restless legs, patients should be referred to a neurologist for evaluation.

The incidence of movement disorders is low and symptoms usually disappear after discontinuation of therapy, in most patients within 4 months of discontinuation of therapy. If the symptoms of parkinsonism persist more than 4 months after discontinuation of the drug, a neurologist should be consulted.

When using the drug there may be cases of falls associated with “unsteady” gait or arterial hypotension, especially in patients taking hypotensive medications (see

Patients with possible increased exposure to trimetazidine should be prescribed with caution:

– with moderate impairment of renal function (see section “Administration and Doses”).

– in patients over 75 years of age (see section “Dosage and administration”).

– in severe hepatic impairment (see section “Caution”).

Influence on driving and operating ability

Because of the possible development of dizziness and other side effects, caution should be exercised when driving vehicles and engaging in other activities requiring increased concentration and quick psychomotor reactions.

Contraindications

Cautious

Patients with severe hepatic impairment, moderate renal impairment (CK 30-60 ml/min), elderly patients over 75 years of age (increased exposure to trimetazidine is possible).

Side effects

Frequency of side effects is classified according to World Health Organization recommendations: Very common (≥1/10); common ( ≥1/100 and <1/10); infrequent

(≥1/1000 and <1/100); rare (≥1/10000 and <1/1000); very rare (<1/10000); frequency unknown – frequency cannot be determined based on available data.

Blood and lymphatic system disorders: frequency unknown- agranulocytosis, thrombocytopenia, thrombocytopenic purpura.

Nervous system disorders: frequent- dizziness, headache; frequency unknown- parkinsonian symptoms (tremor, akinesia, increased tone), “wobbly” gait, restless legs syndrome, other related movement disorders (usually reversible after discontinuation of therapy), sleep disorders (insomnia, somnolence).

Hearing and labyrinth disorders: frequency unknown – vertigo.

Cardiac disorders: frequently – palpitations, extrasystole, tachycardia.

vascular disorders: frequent – arterial hypotension, orthostatic hypotension, which may be accompanied by general weakness, dizziness or loss of balance (falls), especially when concomitant use of hypotensive drugs, “flushes” of blood to the face.

Gastrointestinal disorders: frequent – abdominal pain, diarrhea, dyspepsia, nausea, vomiting; frequency unknown – constipation.

Liver and biliary tract disorders: frequency unknown – hepatitis.

Skin and subcutaneous tissue disorders: frequent – skin rash, skin itching, urticaria; frequency unknown – acute generalized eczematous pustulosis, angioedema.

General disorders and disorders at the site of administration: often – asthenia.

Overdose

Pregnancy use

Similarities