Trimetazidine

Pharmacological properties

mechanism of action. Due to the conservation of energy metabolism in cells suffering from hypoxia or ischemia, trimetazidine prevents a decrease in the level of intracellular ATP, thereby ensuring the proper functioning of ion pumps and a transmembrane sodium-potassium flow while maintaining cell homeostasis. trimetazidine inhibits the β-oxidation of fatty acids by blocking the long-chain 3-ketoacyl-coa-thiolase (3-cat), which increases the oxidation of glucose. in cells under ischemic conditions, the process of generating energy by oxidizing glucose requires less oxygen than the process of generating energy by β-oxidation of fatty acids. increased glucose oxidation optimizes energy processes in cells and, accordingly, supports a sufficient energy metabolism in conditions of ischemia.

Pharmacodynamic effects. In patients with coronary artery disease, trimetazidine acts as a metabolic agent, while maintaining intracellular levels of high-energy phosphates in the myocardium. Effects are achieved without concomitant hemodynamic effects.

Pharmacokinetics C_max trimetazidine in the blood is achieved on average 5 hours after taking the pill. During the day, the concentration in the blood plasma is stable: within 11 hours after taking the pill, the concentration of trimetazidine in the blood plasma is at least 75% C_max. The state of stable concentration is established no later than at the 60th hour. Eating does not affect the pharmacokinetic characteristics of trimetazidine. The volume of distribution is 4.8 l / kg; protein binding is low: according to in vitro measurements, 16%.

Trimetazidine is excreted mainly in the urine, mainly unchanged. T_½ averages 7 hours for healthy young volunteers and 12 hours for people over the age of 65. Complete elimination of trimetazidine is the result of renal clearance, which directly correlates with creatinine clearance and, to a lesser extent, is the result of hepatic clearance, which decreases with age.

Special patient groups

Elderly patients. In elderly patients, an increase in the concentration of trimetazidine is possible due to an age-related decrease in renal function.

Impaired renal function. The concentration of trimetazidine in the blood increases in patients with moderate renal failure (creatinine clearance of 30-60 ml / min) and in patients with severe renal failure (creatinine clearance of 30 ml / min).

Indications

For adults, trimetazidine is indicated for the symptomatic treatment of stable angina pectoris with insufficient effectiveness or intolerance to first-line antianginal drugs.

Application

The drug is prescribed orally 1 tablet (20 mg) 3 times a day with meals. after 3 months of treatment, it is necessary to evaluate the results of treatment and, in the absence of effect, trimetazidine must be canceled.

Patients with renal failure. For patients with moderate impaired renal function (creatinine clearance - 30-60 ml / min), the recommended dose is 1 tablet 2 times a day, that is, in the morning and evening during meals (see SPECIAL INSTRUCTIONS).

Elderly patients. Elderly patients are more sensitive to the action of trimetazidine due to an age-related decrease in renal function (see PHARMACOLOGICAL PROPERTIES). For patients with moderate impaired renal function (creatinine clearance - 30-60 ml / min), the recommended dose is 1 tablet (20 mg) 2 times a day, that is, in the morning and evening during meals.

For elderly patients, the dose should be carefully titrated (see SPECIAL INSTRUCTIONS).

Contraindications

Hypersensitivity to the active substance or to any of the excipients.

Parkinsons disease, symptoms of parkinsonism, tremors, restless legs syndrome and other motor disorders related to the above.

Severe renal failure (creatinine clearance 30 ml / min).

Side effects

From the side of the nervous system: dizziness, headache, symptoms of parkinsonism (tremor, akinesia, muscle hypertonicity, gait instability), restless legs syndrome and other motor disorders that are related to the above and usually go away after treatment is stopped, sleep disorders (insomnia, drowsiness )

On the part of the cardiovascular system: palpitation, extrasystole, tachycardia, arterial hypotension, orthostatic hypotension, which may be associated with malaise, dizziness, or a fall, in particular in patients who use antihypertensive drugs, facial redness.

From the digestive system: nausea and vomiting, abdominal pain, dyspepsia, diarrhea, constipation.

From the hepatobiliary system: hepatitis.

On the part of the immune system, skin and subcutaneous tissue: rash, itching, urticaria, acute generalized pustular exanthema, angioedema.

From the side of the blood system and lymphatic system: agranulocytosis, thrombocytopenia, thrombocytopenic purpura.

General disorders: asthenia.

special instructions

The drug should not be used to relieve angina attacks, with unstable angina or myocardial infarction as the primary therapy at the prehospital stage or in the first days of hospitalization.

In the event of an attack of unstable angina pectoris against the background of current therapy, it is necessary to re-evaluate the patients condition and adjust the treatment (drug therapy and the possibility of revascularization).

Trimetazidine can cause or aggravate symptoms of parkinsonism (tremors, akinesia, muscle hypertonicity), which should be regularly monitored, especially in elderly patients. In doubtful cases, patients should be referred to a neurologist for appropriate examinations.

With the appearance of motor disorders, such as symptoms of parkinsonism, restless legs syndrome, tremors, gait instability, it is necessary to cancel the drug. Such disorders occur infrequently and usually disappear after discontinuation of treatment, in most patients within 4 months after canceling trimetazidine. If symptoms of parkinsonism persist for more than 4 months after discontinuation of the drug, you need to contact a neurologist.

There may be falls associated with gait instability or arterial hypotension, especially in patients who are taking antihypertensive treatment (see ADVERSE EFFECTS).

Caution is advised to prescribe trimetazidine:

patients with moderate renal failure (see APPLICATION);

patients over the age of 75 years (see APPLICATION).

The drug contains lactose. Patients with rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take the drug. Patients with intolerance to certain sugars should consult a doctor.

Use during pregnancy and lactation. Due to the lack of sufficient clinical data, the drug is not recommended to be prescribed during pregnancy.

If it is necessary to use the drug, breast-feeding should be discontinued, since the ability of the drug to penetrate into breast milk has not been studied.

Children. The safety and effectiveness of trimetazidine for children have not been established. There is no data.

The ability to influence the reaction rate when driving vehicles or other mechanisms. Trimetazidine does not affect hemodynamics, however, cases of dizziness and drowsiness have been recorded (see ADVERSE EFFECTS), which may affect the ability to drive vehicles and work with mechanisms.

Interactions

Interactions with other drugs have not been identified.in particular, trimetazidine can be prescribed in combination with heparin, calciparin, vitamin K antagonists, oral lipid-lowering drugs, acetylsalicylic acid, β-adrenergic receptor blockers, calcium antagonists, digitalis drugs (trimethazidine does not affect plasma levels of digoxin).

Overdose

Information on the overdose of trimetazidine is limited.

The treatment is symptomatic.

Storage conditions

In the original packaging at a temperature not exceeding 25 ° C.