Deprenorm MB 70 mg, 30 pcs.

Pharmacodynamics

It has an antihypoxic effect. Trimetazidine prevents decrease in intracellular concentration of adenosine triphosphate (ATP) by maintaining energy metabolism of cells in hypoxia.

Thus, the drug ensures normal functioning of membrane ion channels, transmembrane transport of potassium and sodium ions and preservation of cellular homeostasis.

. Trimetazidine inhibits fatty acid oxidation through selective inhibition of the enzyme 3-ketoacyl-CoA-thiolase (3-CAT) mitochondrial long-chain fatty acid isoform, which leads to increased glucose oxidation and accelerated glucose-oxidized glycolysis, which is responsible for myocardial protection from ischemia. The switch of energy metabolism from fatty acid oxidation to glucose oxidation underlies the pharmacological properties of trimetazidine.

Trimetazidine has been experimentally confirmed to have the following properties:

• maintains energy metabolism of cardiac and neurosensory tissues during ischemia;
• reduces the severity of intracellular acidosis and changes in transmembrane ion flow that occur during ischemia;
• reduces the size of myocardial damage;
• does not directly affect hemodynamic parameters.

In patients with angina pectoris, trimetazidine:

• increases coronary reserve, thereby delaying the onset of exercise-induced ischemia from 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 coronary dysfunction.

Pharmacokinetics

After oral administration, trimetazidine is absorbed from the gastrointestinal tract and reaches maximum plasma concentration after approximately 5 hours. Above 24 hours, plasma concentrations remain above the 75% concentration determined after 11 hours. The equilibrium state is reached after 60 hours. Food intake does not affect the bioavailability of trimetazidine.

The volume of distribution is 4.8 l/kg, which indicates good distribution of trimetazidine in tissues (the degree of binding to plasma proteins is quite low, about 16 % in vitro). Trimetazidine is mainly excreted by the kidneys, mainly unchanged. Renal clearance of trimetazidine directly correlates with creatinine clearance (CK), hepatic clearance decreases with patient age.

Indications

Ischemic heart disease:

Active ingredient

Composition

1 long-acting film-coated tablet contains:

Active substance:

Trimetazidine dihydrochloride 70 mg.

Auxiliary substances:

Hypromellose (hydroxypropyl methylcellulose) 171 mg;

carbomer 2 mg;

silicon dioxide colloid 6 mg;

magnesium stearate 3 mg;

vegetable oil hydrogenated 3 mg;

microcrystalline cellulose 195 mg.

The composition of the film coating:

Opadray II pink 15 mg, including:

polyvinyl alcohol 6 mg,

polyethylene glycol (macrogol) 3.03 mg,

talc 2.22 mg,

titanium dioxide 2.8395 mg,

sunset yellow dye 0.381 mg,

indigo carmine dye 0.2175 mg,

pink crimson [Ponceau 4R] 0.312 mg.

The blister contains 15 tablets. There are 2 blisters in the carton.

How to take, the dosage

Orally, with meals.

Deprenorm® MB is taken 1 tablet of 70 mg once a day (in the morning).

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

Interaction

There are no data on interactions with other drugs.

Special Instructions

Deprenorm® MB is not indicated for the management of angina attacks, for initial therapy of unstable angina or myocardial infarction, or in preparation for or during the first days of hospitalization.

In the event of an angina attack, treatment (drug therapy or revascularization) should be reviewed and adapted.

The drug may cause or worsen symptoms of parkinsonism (tremor, akinesia, increased tone), therefore patients, especially elderly patients, should be monitored regularly. If movement disorders such as parkinsonian symptoms, restless legs, tremor, unsteadiness in the Romberg posture and wobbly gait occur, Deprenorm® MB should be permanently discontinued.

These cases are rare and symptoms usually go away after discontinuation of therapy, in most patients within 4 months of discontinuation. If symptoms of parkinsonism persist more than 4 months after discontinuation of the drug, a neurologist should be consulted. There may be cases of falls associated with unsteadiness in the Romberg posture and a “wobbly” gait or arterial hypotension, especially in patients taking hypotensive drugs (see section “Adverse effects”).

Impact on ability to drive vehicles and other mechanisms requiring high concentration

Because of the possible development of dizziness and other side effects when using Deprenorm® MB, care must be taken when driving vehicles and engaging in other potentially dangerous activities requiring high concentration and quick psychomotor reactions.

Contraindications

With caution: patients with severe hepatic impairment (clinical data are limited); patients with impaired renal function (creatinine clearance greater than 30 ml/min); patients over 75 years.

Side effects

The frequency of side effects noted when taking trimetazidine is given in the following gradation:

Central nervous system: common – dizziness, headache. Unspecified frequency – symptoms of parkinsonism (tremor, akinesia, increased tone), instability in Romberg posture and “wobbly” gait, “restless” legs syndrome, other related motor disorders, usually reversible after discontinuation of therapy. Sleep disorders (insomnia, somnolence).

Cardiovascular system disorders: rare – orthostatic hypotension, “rushes” of blood to the face, palpitations, extrasystole, tachycardia, marked BP reduction.

Blood and lymphatic system disorders: unspecified frequency – agranulocytosis, thrombocytopenia, thrombocytopenic purpura.

In the digestive system: frequently – abdominal pain, diarrhea, dyspepsia, nausea, vomiting. Unspecified frequency – constipation.

Liver and biliary tract: unspecified frequency – hepatitis.

Skin disorders: often – skin rash, itching, urticaria. Unspecified frequency – acute generalized exanthematous pustulosis, Quincke’s edema.

General disorders: often – asthenia.

Overdose

There is only limited information about trimetazidine overdose.

In case of overdose symptomatic therapy should be administered.

Pregnancy use

There are no data on the use of Deprenorm® MB in pregnant women. Animal studies have shown no direct or indirect reproductive toxicity. Reproductive toxicity studies have shown no effect of trimetazidine on reproductive function in rats of either sex. The drug is contraindicated in pregnancy due to a lack of clinical safety data.

There are no data on excretion of trimetazidine or its metabolites into breast milk. The risk to the newborn/infant cannot be excluded. Deprenorm® MB should not be used during breastfeeding.

Similarities