Mildronate solution for intravenous injection 100 mg/ml 5 ml ampoules No. 10

Nosological classification (ICD-10)

• E63 Physical and mental overload
• F10.3 Withdrawal state
• G46 Vascular cerebrovascular syndromes in cerebrovascular diseases
• H34.8 Other retinal vascular occlusions
• H35.0 Background retinopathy and retinal vascular changes
• H35.6 Retinal hemorrhage
• H36.0 Diabetic retinopathy (E10-E14+ with common fourth digit .3)
• H44.8 Other diseases of the eyeball
• I20 Angina [angina pectoris]
• I21 Acute myocardial infarction
• I42.8 Other cardiomyopathies
• I50.0 Congestive heart failure
• I63 Cerebral infarction
• R53 Malaise and fatigue
• Z73.0 Overfatigue
• Z73.2 Lack of rest and relaxation
• Z73.6 Restrictions in activity caused by decreased ability to work

Reviews of Mildronate

Reviews about Mildronate on forums are mostly positive . The unique mechanism of action of this drug allows it to be widely used to eliminate problems with the cardiovascular system, as well as as a means of increasing performance in healthy people who are subject to frequent physical and intellectual overload.

Both patients in cardiology departments, doctors, and athletes note the fact that Mildronate provokes a tonic effect. Its use significantly improves memory function, accelerates thought processes, increases dexterity, endurance and the degree of body resistance to adverse factors.

Reviews from cardiologists confirm the data of numerous studies that have shown that the use of Mildronate in capsules and in the form of a solution for injections can reduce the incidence of repeated myocardial infarction .

Reviews from patients about Mildronate allow us to conclude that the drug is simply necessary for people whose activities are associated with increased stress on the body, as well as during the recovery period after prolonged alcohol abuse, with pain and burning in the heart, VSD and other pathologies of the cardiovascular system .

The average rating for this product is quite high. However, sometimes you come across negative reviews about Mildronate. It is important to remember that, like any other drug, Mildronate gives a good result only if its dose and concomitant treatment (if necessary) are selected correctly.

Composition and release form

in ampoules of 5 ml, in a blister 5 pcs.; There are 2 blisters in a cardboard pack.

10 pcs in blister; in a cardboard pack there are 4 blisters (250 mg) or 6 blisters (500 mg).

pharmachologic effect

Pharmacological action: cardioprotective, antihypoxic, angioprotective, antianginal.

Under conditions of increased stress, Mildronate® restores the balance between the supply and need of cells for oxygen, eliminates the accumulation of toxic metabolic products in cells, protecting them from damage; has a tonic effect. As a result of its use, the body acquires the ability to withstand stress and quickly restore energy reserves. Thanks to these properties, Mildronate® is used to treat various disorders of the cardiovascular system, blood supply to the brain, as well as to increase physical and mental performance. As a result of a decrease in carnitine concentration, gamma-butyrobetaine, which has vasodilating properties, is intensively synthesized. In case of acute ischemic damage to the myocardium, Mildronate® slows down the formation of the necrotic zone and shortens the rehabilitation period. In heart failure, it increases myocardial contractility, increases exercise tolerance, and reduces the frequency of angina attacks. In acute and chronic ischemic disorders of cerebral circulation, it improves blood circulation in the ischemic area and promotes the redistribution of blood in favor of the ischemic area. Effective in cases of vascular and dystrophic pathology of the fundus. The drug eliminates functional disorders of the central nervous system in patients with chronic alcoholism with withdrawal syndrome.

Alcohol compatibility

The active substance of Mildronate is excreted from the body within 12 hours, therefore, after this time, the risk of interaction of the drug with another active substance is extremely low or completely absent.

In general, drinking alcohol during treatment with Mildronate is not prohibited; however, if this drug is used to treat a cardiovascular disease or a cerebral circulatory disorder, the patient is still advised to stop drinking alcohol.

This is due to the fact that taking the drug in combination with alcohol can negate all the positive results that have been achieved in treating the disease.

Taking Mildronate with alcohol can provoke:

• tachycardia;
• pronounced allergic reactions ;
• sharp fluctuations in blood pressure;
• dyspeptic symptoms.

The poor compatibility of Mildronate with alcohol is due to an increased risk of various types of complications and the likelihood of a relapse of the disease. For this reason, alcohol should be excluded for the entire period of treatment with the drug.

Indications for the drug MILDRONATE®

For adults:

All dosage forms

complex therapy of coronary artery disease (angina pectoris, myocardial infarction);

chronic heart failure and dyshormonal cardiomyopathy, as well as complex therapy of acute and chronic disorders of the blood supply to the brain (cerebral strokes and cerebrovascular insufficiency);

withdrawal syndrome in chronic alcoholism (in combination with specific therapy for alcoholism);

decreased performance, physical stress, incl. in athletes.

Injection

hemophthalmos and retinal hemorrhages of various etiologies;

thrombosis of the central retinal vein and its branches;

retinopathy of various etiologies (diabetic, hypertensive).

special instructions

Due to the fact that the drug can provoke a stimulating effect, it is recommended to use it in the first half of the day.

There are no data regarding the ability of Mildronate to change the reaction rate and influence transport control.

The drug is prescribed with caution to people with liver and/or kidney pathologies.

Experience in treating patients with myocardial infarction and unstable angina shows that the active substance Mildronate is not a first-line drug for ACS.

Interaction

Enhances the effect of coronary dilatants, some antihypertensive drugs, cardiac glycosides. Can be combined with antianginal drugs, anticoagulants, antiplatelet agents, antiarrhythmic drugs, diuretics, bronchodilators. Due to the possible development of moderate tachycardia and arterial hypotension, caution should be exercised when combined with nitroglycerin, nifedipine, alpha-blockers, antihypertensive agents and peripheral vasodilators.

Directions for use and doses

Capsules - orally, injection solution - IV, in the first half of the day.

Cardiovascular diseases, adults, as part of complex therapy: orally (capsules) - 0.5-1 g per day or intravenously - 5-10 ml of solution for injection, in 1 or 2 doses. The course of treatment is 4–6 weeks.

Cardialgia due to dyshormonal myocardial dystrophy - orally (capsules), 0.25 g 2 times a day. The course of treatment is 12 days.

Cerebrovascular accidents: acute phase - intravenously, 5 ml of solution for injection once a day for 10 days, then orally (capsules), 0.5–1 g per day. The course of treatment is 4–6 weeks. Chronic disorders - orally (capsules), 0.5–1 g per day. The course of treatment is 4–6 weeks. Repeated courses (usually 2-3 times a year) are possible after consulting a doctor.

Vascular pathology and dystrophic diseases of the retina: parabulbar, 0.5 ml of injection solution for 10 days.

Mental and physical overload, incl. for athletes: the optimal dosage is 1 g/day (0.25 g 4 times a day or 0.5 g 2 times a day). The course of treatment is 10–14 days. If necessary, treatment is repeated after 2–3 weeks. For athletes - orally (capsules), 0.5–1 g 2 times a day before training. The duration of the course during the preparatory period is 14–21 days, during the competition period — 10–14 days.

Chronic alcoholism: orally (capsules), 0.5 g 4 times a day; IV, 5 ml of solution for injection 2 times a day. The course of treatment is 7–10 days.

Mildronate solution for intravenous injection 100 mg/ml 5 ml ampoules No. 10

INSTRUCTIONS FOR MEDICAL ADMINISTRATION

1. NAME OF THE MEDICINE

Trade name: MILDRONATE solution for injection 0.5 g/5 ml International nonproprietary name: Meldonium (.Meldonium)

2. GENERAL CHARACTERISTICS Description

Colorless transparent liquid.

3. COMPOSITION OF THE MEDICINE

1 ampoule (5 ml) contains 0.5 g of meldonium. Excipient: water for injection.

4. FORM OF RELEASE

Injection.

5. MEDICINE CLASSIFICATION CODE

Other drugs for the treatment of heart disease. ATX code: C01EB

6. PHARMACOLOGICAL PROPERTIES Pharmacodynamics

Meldonium is a precursor to carnitine, a structural analogue of gamma butyrobetaine (GBB), in which one carbon atom is replaced by a nitrogen atom. Meldonium, by reversibly inhibiting gamma butyrobetaine hydroxylase, reduces the biosynthesis of carnitine and prevents the transport of long-chain fatty acids through cell membranes, thus preventing the accumulation of strong detergents in cells - activated forms of non-oxidized fatty acids, preventing damage to cell membranes. When the concentration of carnitine decreases under ischemic conditions, β-oxidation of fatty acids is delayed and oxygen consumption in cells is optimized, glucose oxidation is stimulated and ATP transport from sites of biosynthesis (mitochondria) to sites of consumption (cytosol) is resumed. Essentially, the cells are supplied with nutrients and oxygen, and the use of these substances is optimized. In turn, with an increase in the biosynthesis of the carnitine precursor, i.e. GBB, NO synthetase is activated, resulting in improved rheological properties of the blood and a decrease in peripheral vascular resistance. When the concentration of meldonium decreases, the biosynthesis of carnitine increases again and the amount of fatty acids in the cells increases. It is believed that due to the effectiveness of meldonium, the tolerance of cellular load increases (with a change in the amount of fatty acids). Effect on the heart and circulatory system

In animal studies, it was found that meldium is positive for the contractile activity of the myocardium, it has a protective effect (including in relation to alcohol and catecholamines), it helps to disrupt the heart rhythm, and reduces the area of ​​myocardial infarction. Coronary heart disease (stable angina pectoris) Analysis of clinical data from the course of use of meldonium in the treatment of stable angina pectoris in combination with other antianginal drugs showed that the drug reduces the frequency and intensity of angina attacks, as well as the amount of glyceryl trinitrate used. The drug has an antiarrhythmic effect in patients with coronary heart disease (CAD) and with ventricular extrasystoles; a lesser effect is observed in patients with supraventricular extrasystoles. The drug has the ability to reduce oxygen consumption at rest, which is considered an effective criterion for antianginal therapy of CAD. Meldonium has a beneficial effect on atherosclerotic processes in the coronary and peripheral vessels, reducing total serum cholesterol levels and the atherogenic index. Chronic Heart Failure Clinical studies have examined the role of meldonium in the treatment of chronic heart failure due to coronary artery disease and have noted its ability to increase exercise tolerance and work output in patients with heart failure. The effectiveness of meldonium in the case of heart failure 1-111 NYHA functional class has been tested. It has been established that the use of meldonium in combination with other traditional drugs for the treatment of heart failure improves myocardial inotropic function and increases exercise tolerance, improves the quality of life of patients without causing severe side effects. However, it has been noted that meldonium may cause slight hypotension. Effect on the central nervous system In animal experiments, meldonium has been shown to have an antihypoxic effect and an effect on cerebral circulation. The drug optimizes the redistribution of cerebral circulation volume in favor of ischemic foci and increases the strength of neurons under hypoxic conditions. The drug has a stimulating effect on the central nervous system: it increases motor activity and physical endurance, stimulates behavioral reactions, and also {_) exhibits an anti-stress effect (stimulation of the sympathoadrenal system, accumulation of catecholamines in the brain and adrenal glands, protection against changes in internal organs caused by stress) . Efficacy in neurological diseases The effect of meldonium on the rehabilitation process in patients with neurological disorders (after diseases of the blood vessels of the brain, brain surgery, trauma, tick-borne encephalitis) has been studied. The results of testing the therapeutic activity of meldonium indicate its dose-dependent positive effect on physical endurance and restoration of functional independence during the recovery period. When analyzing changes in individual and total intellectual functions after using the drug, a positive effect on the recovery process of intellectual functions during the recovery period was established. It has been established that meldonium improves the convalescent quality of life (mainly due to the renewal of the physical function of the body), and the drug eliminates mental disorders. ^tshshas^

Meldonium is characterized by a positive effect on the regression of the funcodal system and reduces disorders in patients with neurological deficits.

recovery. The general neurological condition of patients improves (reduction of damage to brain nerves and pathology of reflexes, regression of paresis, improvement of coordination of movements and autonomic functions). Pharmacokinetics Pharmacokinetic studies were conducted in healthy volunteers using a single dose of 25, 50, 100, 200, 400, 800 or 1500 mg of meldonium. It has been established that the maximum concentration of meldonium in blood plasma (Cmax) and the area under the concentration-time curve (AUC) increase in proportion to the dose applied. The time to reach maximum concentration (Tmax) was 1-2 hours and the half-life of elimination (t/z) was 4 hours. Excretion of the drug in urine increases with doses up to 400 mg; When using doses greater than 400 mg, excretion remains virtually unchanged. The pharmacokinetics of meldonium is affected by the presence of food in the stomach, i.e. food delays the absorption of meldonium after a single dose of 400 mg. With repeated use of meldonium at a dose of 400-800 mg per day (twice a day for 7 days or once a day for eight days), the equilibrium concentration of the drug in plasma is achieved 72-96 hours after the first dose. Metabolism studies in experimental animals have shown that meldonium is metabolized primarily in the liver. 7. INDICATIONS FOR USE Mildronate is used as part of combination therapy in the following cases: - cardiovascular diseases: stable angina pectoris, chronic heart failure (NYHA IIII functional class), cardiomyopathy, functional disorders of the cardiovascular system; - acute and chronic cerebrovascular accidents; - reduced performance, physical and psycho-emotional overload; - recovery period after cerebrovascular accidents, head injuries and encephalitis. 8. METHOD OF APPLICATION AND DOSAGE Method of application: intravenous injection. Adults are prescribed 0.5-1.0 g per day, using the entire dose at once or dividing it by 2 times. The maximum daily dose is 1.0 g. Due to the possible development of an stimulating effect, it is recommended to use it in the first half of the day. There are no special recommendations for use in elderly patients. For elderly patients with impaired liver and/or kidney function, lower doses are required. Patients with impaired liver and/or kidney function require lower doses. Use in children is contraindicated due to the lack of data on effectiveness and safety. The duration of treatment is 4-6 weeks. If you miss another dose of the drug, take it immediately. Do not take a double dose to replace a missed dose. Continue taking as recommended by your doctor.

9. SIDE EFFECTS

In the following, the listed side effects are classified according to organ system groups; when indicating the frequency of occurrence, the following classification is used: very often (>1/10), often (>1/100, <1/10), less often (>1/1000, <1/100), rarely (>1/10,000 , <1/1000), very rare (<1/10,000), including isolated cases. Blood and lymphatic system disorders Eosinophilia*. Immune system disorders Common: allergic reactions. Cardiac disorders In some cases: tachycardia. Disorders of the circulatory system In some cases: low blood pressure. Nervous system disorders Common: headache, agitation*. General disorders General weakness*. * Insufficient number of observations to determine frequency of occurrence. If the listed adverse reactions occur, as well as if an adverse reaction not mentioned in the instructions occurs, you should consult a doctor.

10. CONTRAINDICATIONS

- Hypersensitivity to meldonium. — Renal and liver failure (there is insufficient data on the safety of use). — Pregnancy, lactation period. — Children under 18 years of age. I. OVERDOSE No cases of overdose with mildronate have been reported. The drug is low-toxic and does not cause threatening side effects. Symptoms: in case of low blood pressure, headaches, dizziness, tachycardia, and general weakness are possible. Treatment is symptomatic. In case of severe overdose, it is necessary to monitor liver and kidney functions. 12. PRECAUTIONS Patients with a history of chronic liver and kidney diseases should be careful when using the drug (monitoring liver and kidney function). Pregnancy and breastfeeding To determine the effect of meldonium on pregnancy, embryo/fetal development, childbirth and postpartum development, animal studies are not sufficient. The potential risk to humans is unknown, so this drug should not be used during pregnancy. It is not known whether the drug is excreted into mother's milk. If necessary, breastfeeding should be stopped.

Impact on the ability to drive vehicles and maintain moving machinery. A study of the effect on the ability to drive vehicles and maintain moving machinery has not been conducted. Many years of experience in the treatment of acute myocardial infarction and unstable angina in cardiology departments show that mildronate is not a first-line drug for acute coronary syndrome.

13. INTERACTION WITH OTHER MEDICINES

Mildronate can be used in conjunction with long-acting nitrates and other antianginal agents (stable exercise angina), cardiac glycosides and diuretics (heart failure). Mildronate can also be combined with anticoagulants, antiplatelet agents, antiarrhythmic drugs and other drugs that improve microcirculation. It must be borne in mind that mildronate may enhance the effect of glyceryl trinitrate, nifedipine, beta blockers, other antihypertensive drugs and peripheral vasodilators.

14. CONDITIONS AND STORAGE DURATION

Store at a temperature no higher than 25 C. Do not freeze! Keep out of the reach of children. Shelf life - 4 years. Do not use after the expiration date stated on the package.

15. HOLIDAY CONDITIONS

On prescription.

16. PACKAGING

5 ml in a clear glass ampoule with a line or break point. 5 ampoules in a cell package made of polyvinyl chloride film. 2 cell packs with instructions for use in a cardboard pack.

17. INFORMATION ABOUT THE MANUFACTURER (APPLICANT) Registration Certificate Holder

JSC Grindeks. St. Krustpils, 53, Riga, LV-1057, Latvia Phone: +371 67083205 Fax: +371 67083505 Email Manufacturer(s) HBM Pharma s.r.o. St. Sklabinska 30, Martin 036 80, Slovakia Date of text correction: March 2013