INSTRUCTIONS FOR MEDICAL USE

METOLAN

Trade name of the drug: Metolan

Active substance (INN): Meldonium

Dosage form: Solution for injection.

Contents:

5 ml of the solution (1 ampoule) contains:

The active substance: Meldonium – 500 mg.

Excipients: Water for injection.

Description: Colorless, transparent liquid.

Pharmacotherapeutic group: Metabolic agents.

ATX code: C01EB22

Pharmacological properties

Meldonium is a structural analogue of gamma-butyrobetaine, a substance that is found in every cell of the human body.

Under increased stress, the drug restores the balance between supply and demand of cells for oxygen, eliminates the accumulation of toxic products of metabolism in the cells, protecting them from damage; it also has a tonic effect. As a result of its use, the body acquires the ability to withstand the load and quickly restore energy reserves. Due to these properties, the drug is used to treat various disorders of the cardiovascular system, blood supply to the brain, as well as to increase physical and mental performance. In acute ischemic myocardial damage, the drug slows down the formation of the necrotic zone and shortens the rehabilitation period. In heart failure, it increases myocardial contractility, increases exercise tolerance, reduces the frequency of angina attacks. In acute and chronic ischemic cerebral circulatory disorders improves blood circulation in the focus of ischemia, contributes to the redistribution of blood in favor of the ischemic area. It is effective in case of vascular and dystrophic ocular pathology. The drug eliminates the functional disorders of the nervous system in patients with chronic alcoholism during withdrawal syndrome.

Pharmacokinetics

Bioavailability of the drug after intravenous (IV) injection is 100%. Maximal concentration (Cmax) in blood plasma is reached immediately after administration. The drug is metabolized in the body to form two main metabolites, which are excreted by the kidneys. The elimination half-life (T1/2) is 3-6 hours.

Indications for use

As part of the complex therapy of coronary heart disease (angina pectoris, myocardial infarction), chronic heart failure and dyshormonal cardiomyopathy, and as part of the complex therapy of acute and chronic blood circulation disorders of the brain (stroke and cerebrovascular insufficiency).

Hemophthalmus and retinal hemorrhages of various etiologies, central retinal vein thrombosis and its branches, retinopathies of various etiologies (diabetic, hypertensive).

Reduced work capacity, physical overexertion, including in athletes. Withdrawal syndrome in chronic alcoholism (in combination with specific therapy).

Dosage and administration

Because of the possible development of the excitatory effect it is recommended to use in the morning.

Cardiovascular diseases

As part of the complex therapy of 0.5-1 g per day by IV (5-10 ml of a solution for injection 500 mg/5 ml), applying the entire dose at once or dividing it into 2 times. The course of treatment is 4-6 weeks.

Impaired cerebral circulation

Acute phase – 0.5 g 1 time a day v/v for 10 days, then switch to oral dosage form. The total course of treatment is 4-6 weeks.

Chronic disorders

• Oral dosage form is used. Repeated courses (usually 2-3 times a year) are possible after consultation with the doctor.

Vascular pathology and dystrophic retinal diseases

• Parabulbar 0.5 ml of 500 mg/5 ml solution for 10 days.

Mental and physical overload, including in athletes:

• Adults 0.5 g v/v (5-10 ml of 500 mg/5 ml solution for injection) once daily. The course of treatment is 10-14 days. If necessary, treatment should be repeated in 2-3 weeks.

Chronic alcoholism.

IV – 0.5 g 2 times a day. The course of treatment – 7-10 days.

Side effects

The cardiovascular system: rare – tachycardia, changes in blood pressure.

The central nervous system (CNS): rare – psychomotor agitation.

The digestive system: rare – dyspeptic symptoms.

Allergic reactions: rare – skin itching, redness, rash, swelling.

Contraindications

• Increased intracranial pressure (including with impaired venous outflow, intracranial tumors);
• Organic CNS lesions;
• pregnancy, lactation;
• hypersensitivity to the drug;
• under 18 years of age.

Drug interactions

Increases the effect of coronadilators, some hypotensive drugs, cardiac glycosides. It can be combined with antianginal drugs, anticoagulants, antiaggregants, antiarrhythmic drugs, diuretics and bronchodilators. Caution must be exercised when combining with nitroglycerin, nifedipine, alpha-adrenoblockers, hypotensive agents and peripheral vasodilators because of possible development of moderate tachycardia and arterial hypotension.

Special indications

Caution should be exercised in patients with chronic liver and renal diseases during long-term use of the drug. There are no sufficient data on the use of meldonium in children.

Many years of experience in the treatment of acute myocardial infarction and unstable angina in cardiology departments show that meldonium is not a first-line drug for acute coronary syndrome.

Use during pregnancy and lactation.

The safety of using the drug during pregnancy has not been proven.

To avoid possible adverse effects on the fetus, it is not prescribed during pregnancy.

It is not known whether the drug is excreted with the milk of the mother. If the drug treatment for the mother is necessary, breastfeeding of the child is stopped.

Effect on the ability to drive vehicles and operate other mechanisms.

There are no data on adverse effects of the drug on the speed of psychomotor reactions.

Form of production

Solution for injection 500 mg/5 ml in 5 ml ampoules N5(1×5), N10(2×5)

Storage conditions

Store in a dry place, protected from light, at a temperature not exceeding 25°C. Keep out of the reach of children! Do not freeze!

Shelf life

4 years. Do not use after the expiration date.

Conditions of dispensing from pharmacies

Released by doctor’s prescription.

INSTRUCTIONS FOR MEDICAL USE

ALOTREM NEO

Trade name of the drug: Alotrem® Neo

Active substance (INN): Levocarnitine/L-carnitine

Dosage form: Solution for injection.

Contents:

5 ml of solution (1 ampoule) contains:

Active ingredient: L-carnitine-1000 mg.

Excipients: Hydrochloric acid (to create the required pH), water for injection.

Description: colorless to light yellow transparent solution.

Pharmacotherapeutic group: agents for correction of metabolic processes.

ATX code: A16AA01

Pharmacological properties

The drug for the correction of metabolic processes. L-carnitine – a natural substance, related to the B vitamins. Participates in metabolic processes as a carrier of long-chain fatty acids (including palmitic) through cell membranes from the cytoplasm to the mitochondria, where these acids are oxidized (beta-oxidation process) to form a large amount of metabolic energy (in the form of ATP).

The drug improves metabolism and energy supply of tissues; corrector of metabolic processes, stimulator of energy metabolism.

The drug replenishes blood alkaline reserve, restores autoregulation of cerebral hemodynamics and increases blood supply to the affected area, accelerates reparative processes in the lesion and has an anabolic effect. It has a neurotrophic effect, inhibits the development of apoptosis, limits the lesion area and restores the structure of nervous tissue. The drug has an anabolic and lipolytic effect. Normalizes protein and fat metabolism, reduces excess body weight, reduces muscle fat, increases resistance to exercise, increases motor activity.

The product increases the secretion and enzymatic activity of gastric and intestinal juices, improves digestion.

The drug normalizes elevated basal metabolism in hyperthyroidism, being a partial antagonist of thyroxine.

Pharmacokinetics

During parenteral administration, the drug penetrates well into all tissues, high concentrations are formed in skeletal muscle and myocardium. It is excreted by kidneys mainly as acyl esters, free carnitine is reabsorbed.

Indications for use

• Secondary carnitine deficiency in patients with end-stage renal failure who have undergone hemodialysis, because free carnitine (which is usually reabsorbed by the kidneys) is eliminated and the acyl esters (released by the healthy kidneys) are stored;
• in carnitine deficiency in preterm infants on total parenteral nutrition. Injection of nutrients into the vein eliminates their initial passage through the intestinal wall and the liver. As a result, there is an excess of lipids in the blood plasma, which depresses the rate of all biochemical reactions (in particular, the utilization of methyl groups of methionine is impaired);
• carnitine deficiency in patients with dramatically increased carnitine consumption (including hypoxia, diphtheria, taking valproic acid drugs);
• Anorexia, lack of weight gain and stunting in children;
• Cardiomyopathy (myocardial utilization of fatty acids as an energy source is very intensive, so the need for carnitine increases, after its administration an increase in muscle contractility, prevention of further muscle degeneration, normalization of the ECG is noted);
• Skeletal muscle weakness and myopathy;
• distress syndrome in premature infants;
• organic acidemia.

This pathology results from congenital or genetic abnormalities of normal organic acid metabolism. In such patients, acyl CoA metabolites, such as propionyl-CoA, accumulate in cells, turn into acyl esters of carnitine and are removed from cells with it, leading to its intracellular deficiency. Propionic acid residue in the liver inhibits oxidative phosphorylation, thus impairing its function;

• in the treatment of diseases that require the use of anabolic (nonsteroidal) agents. The drug is used in the treatment of acute hypoxic conditions (acute cerebral hypoxia, ischemic stroke, transient ischemic attack), skin diseases, chronic gastritis, and chronic pancreatitis with decreased secretory function.

The drug is prescribed in acute, subacute and recovery periods of cerebrovascular disorders. It is used for discirculatory encephalopathy and various traumatic and toxic lesions of the brain, in the recovery period after surgical interventions. The drug is indicated for ischemic heart disease (stenocardia, acute myocardial infarction, postinfarction states), hypoperfusion due to cardiogenic shock and other myocardial metabolic disorders.

The drug is used as part of complex therapy:

• intensive physical activity and psycho-emotional stress: to increase working capacity, endurance, reduce fatigue, including, in elderly people;
• During rehabilitation after diseases, surgeries and injuries, including for acceleration of tissue regeneration;

Directions for use and dosages

The drug is administered intramuscularly, intravenously slowly (2-3 minutes) or by infusion.

Adults and children over 12 years of age.

The daily dose is usually 1-3 g in 3-4 injections. The initial dose is 1 g/day and after examination of the patient the dose may be increased to 3 g/day depending on the condition.

In primary or secondary carnitine deficiency in acute decompensation, the drug is prescribed in a dose of 50-100 mg/kg/day in 3-4 injections. If necessary, the drug may be administered in a higher dose.

In carnitine deficiency secondary deficiency in patients with terminal stage of chronic renal failure, receiving hemodialysis the drug is prescribed in dose 20 mg/kg/day at the end of each hemodialysis procedure (in three hemodialysis procedures during a week).

The duration of the IV treatment is not more than 3 months and the period required to restore normal levels of levocarnitine in muscles.

The need for repeated treatment is determined by the plasma content of levocarnitine, which should be monitored regularly.

Pathology	Scheme	Course duration
Acute disturbances of cerebral circulation	1 g/day i/v 0.5 g/day i/v	3 days 7 days After 10-12 days repeated courses of 3-5 days are possible
Subacute and recovery period after cerebral circulatory disorders, discirculatory encephalopathy and other brain lesions	0.5-1 g/day intravenously (drops, streams) or intramuscularly ( 2-3 times a day) without dilution	3-7 days If necessary, in 12-14 days a second course is prescribed
Acute myocardial infarction, acute heart failure	3-5 g/day divided into 2 to 3 doses	In the first 2-3 days, with subsequent reduction of the dose by half.
Cardiogenic shock	3-5 g/day divided into 2 to 3 doses	Until the patient comes out of shock

Children under 12 years of age.

In case of primary or secondary carnitine deficiency in acute decompensation the drug is prescribed in a dose of 50-100 mg/kg/day in 3-4 injections.

In carnitine deficiency secondary deficiency in patients with terminal stage of chronic kidney failure who are hemodialysis patients this preparation is prescribed in dose 10-20 mg/kg/day at the end of each hemodialysis procedure (3 hemodialysis procedures during a week). The duration of treatment with the drug when administered intravenously is not more than 3 months. Usually a repeated course of therapy is prescribed.

Side effects

Allergic reactions, muscle weakness (in patients with uremia), pain in the epigastric region are possible.

During rapid injection, pain along the vein is possible; it will disappear if the injection speed is reduced.

Contraindications

Hypersensitivity to the drug components.

Caution: The drug should be used in case of diabetes mellitus and during pregnancy and lactation (breast-feeding) only if absolutely necessary.

Drug interactions

Before prescribing the drug, it should be found out which drugs the patient is taking. The drug may be combined with various anabolic agents; with drugs with antioxidant and/or antihypoxant activity. Excessive doses of choline inhibit levocarnitine synthesis and activity. Glucocorticosteroids promote accumulation of levocarnitine in tissues (except liver). Anabolic agents enhance the effect of carnitine.

Special indications

It is recommended to monitor therapy by measuring free and acyl levocarnitine concentrations in plasma and urine to determine an adequate dose of the drug. Levocarnitine is not addictive because it is an endogenous substance of the human body. Administration of the drug to patients with diabetes mellitus receiving insulin or oral hypoglycemic agents may cause hypoglycemia. Therefore, in this category of patients during treatment with the drug, blood glucose content should be constantly monitored for immediate correction of hypoglycemic drugs dosing regimen.

Effect on the ability to drive motor transport and operate machinery.

The drug does not affect the ability to drive vehicles and other potentially dangerous activities.

Overdose

There are no data concerning toxicity in case of overdose of levocarnitine. Tolerability of the drug should be controlled during the first week of treatment and after each increase in the dose taken.

Symptoms: diarrhea.

Treatment: carry out symptomatic therapy.

Form of production

Solution for injection 1000 mg/5 ml in ampules of 5 ml, #5, #10.

Storage Conditions

Store in a dry place, protected from light, at a temperature not exceeding 25°C. Keep out of reach of children!

Shelf life

3 years. Do not use after the expiration date.

Conditions for dispensing from pharmacies

Released by a doctor’s prescription.