Instructions for medical use

medicinalcremedies

MILDRONATE ®

Trade name

MILDRONATE ®

International nonproprietary name

Meldonium

Dosage form

Solution for injection 0.5 g/5 ml, 5 ml

Compound

1 ampoule (5 ml solution) contains:

active substance- meldonium dihydrate 500 mg,

excipient - water for injections.

Description

Transparent colorless liquid

Pharmacotherapeutic group

Other drugs for the treatment of heart diseases. Meldonium.

ATX code C01EB22

Pharmacological properties

Pharmacokinetics

Suction

After intravenous administration of multiple doses of meldonium, the maximum concentration (C max) reached 25.50 ± 3.63 μg/ml.

Bioavailability was increased in individuals with increases in Cmax, AUC, and half-life (t1/2), in patients with liver cirrhosis, and in patients with severe renal impairment. When administered intravenously, the AUC after single and repeated doses of meldonium is different. These results indicate the possible accumulation of meldonium in blood plasma.

Distribution

Meldonium from the bloodstream quickly spreads to tissues; has a high affinity for heart tissue. Plasma protein binding increases with time after dosing. Meldonium and its metabolites partially overcome the placental barrier. Studies on the release of meldonium into human breast milk have not been conducted.

Metabolism

Meldonium is primarily metabolized in the liver.

Removal

Renal excretion plays a significant role in the elimination of meldonium and its metabolites. After a single intravenous administration of 250 mg, 500 mg and 1000 mg doses of meldonium, the half-life of early elimination of meldonium is 5.56-6.55 hours, the final half-life of elimination is 15.34 hours.

Special patient groups

Elderly patients

The dose of meldonium should be reduced in elderly patients with impaired liver or kidney function, in whom bioavailability is increased.

Patients with renal impairment

In patients with impaired renal function and increased bioavailability, the dose should be reduced. There is an interaction between the renal reabsorption of meldonium or its metabolites (eg, 3‑hydroxymeldonium) and carnitine, resulting in increased renal clearance of carnitine. There is no direct effect of meldonium, gamma-butyrobetaine (GBB) and the combination of meldonium/GBB on the renin-angiotensin-aldosterone system.

Patients with liver dysfunction

In patients with liver impairment and increased bioavailability, the dose of meldonium should be reduced. No changes in liver function tests were observed in humans following doses of 400-800 mg. Possible infiltration of fats into liver cells cannot be excluded.

Pediatric population

There is no data on the safety and effectiveness of the use of meldonium in children and adolescents under the age of 18 years, therefore the use of meldonium in this group of patients is contraindicated.

Pharmacodynamics

Meldonium is a structural analogue of the carnitine precursor gamma butyrobetaine (GBB), in which one of the carbon atoms is replaced by a nitrogen atom. Under conditions of increased stress, meldonium 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; also 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, meldonium 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, GBB is intensively synthesized, which has vasodilating properties. In the case of acute ischemic damage to the myocardium, meldonium 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. In case of neurological disorders (after cerebrovascular accidents, brain surgery, head injuries, tick-borne encephalitis), it has a positive effect on the recovery process of physical and intellectual functions during the recovery period.

Indications for use

In complex therapy in the following cases:

• diseases of the heart and vascular system: stable angina pectoris, chronic heart failure (NYHA I‑III functional class), cardiomyopathy, functional disorders of the heart and vascular system;
• acute and chronic ischemic disorders of cerebral circulation;
• decreased performance, physical and psycho-emotional stress;
• during the recovery period after cerebrovascular disorders, head injuries and encephalitis.

Directions for use and doses

Intravenously. The use of the drug does not require special preparation before administration.

Due to the possible stimulating effect, the drug is recommended to be used in the first half of the day.

Cardiovascular diseases and cerebrovascular disorders

As part of complex therapy, 500 mg-1000 mg per day intravenously (5-10 ml of injection solution 0.5 g/5 ml), taking the entire dose at once or dividing it into 2 doses. The maximum daily dose is 1000 mg.

Reduced performance, overexertion and recovery period

500 mg (5 ml) per day intravenously. The maximum daily dose is 500 mg.

The duration of treatment is 4-6 weeks.

The course of treatment can be repeated 2-3 times a year.

Elderly patients

In elderly patients with liver and/or kidney disease, the dose of meldonium should be reduced.

Patients with renal impairment

Since the drug is eliminated from the body through the kidneys, patients with mild to moderate renal impairment should use a lower dose of meldonium.

Patients with liver disorders

Patients with mild to moderate hepatic impairment should use a lower dose of meldonium.

Pediatric population

There is no data on the safety and effectiveness of meldonium in children and adolescents under the age of 18, therefore the use of this drug in children and adolescents is contraindicated.

Side effects

Often

Allergic reactions (hypersensitivity, allergic dermatitis, urticaria, angioedema, anaphylactic reaction)

Headaches

Dyspepsia (feeling of heaviness, bloating, fullness, pain and discomfort in the epigastrium, nausea)

Rarely

Agitation, fear, obsessive thoughts, sleep disturbance

Paresthesia, tremor, hypoesthesia, tinnitus, vertigo, dizziness, gait disturbance, lightheadedness, loss of consciousness

Tachycardia/sinus tachycardia, atrial fibrillation, arrhythmia, chest discomfort/chest pain

Fluctuations in blood pressure, hypertensive crisis, hyperemia, pale skin

Sore throat, cough, dyspnea, apnea

Dysgeusia (metallic taste in the mouth), loss of appetite, nausea, vomiting, gas accumulation, diarrhea, abdominal pain

Rash (general/macular/papular), itching

Back pain, muscle weakness, muscle spasms

Pollakiuria

General weakness, tremor, asthenia, general swelling, swelling of the face, swelling of the legs, feeling hot, feeling cold, cold sweat

Abnormalities in the electrocardiogram (ECG), acceleration of the heart, eosinophilia

Contraindications

Hypersensitivity to meldonium dihydrate

Severe liver and/or renal failure, due to the lack of data on the safety of use

Pregnancy and lactation, due to the lack of data on the clinical use of the drug during this period

Children under 18 years of age, due to the lack of data on clinical use during this period

Drug interactions

Meldonium can be used together with long-acting nitrates and other antianginal agents for the treatment of stable angina pectoris, together with cardiac glycosides and diuretics for the treatment of heart failure.

Meldonium can be combined with anticoagulants, antiplatelet agents, antiarrhythmic drugs and drugs that improve microcirculation.

Meldonium may enhance the effect of drugs containing glyceryl trinitrate, nifedipine, beta-blockers, other antihypertensive drugs and peripheral vasodilators.

In patients with chronic heart failure, taking meldonium and lisinopril simultaneously to reduce symptoms, a positive effect of combination therapy was revealed (vasodilation of the main arteries, improvement of peripheral circulation and quality of life, reduction of psychological and physical stress).

When meldonium was used in combination with orotic acid to reverse ischemia/reperfusion injury, additive pharmacological effects were observed.

As a result of simultaneous use Sorbifer and meldonium in patients with anemia caused by iron deficiency, the composition of fatty acids in erythrocytes improved.

Meldonium helps reverse cardiac pathology caused by azidothymidine (AZT) and indirectly affects the oxidative stress responses caused by AZT, leading to mitochondrial dysfunction. The use of meldonium in combination with AZT or other drugs for the treatment of acquired immunodeficiency syndrome (AIDS) has a positive effect on AIDS therapy.

In a test of ethanol-induced balance reflex loss, meldonium decreased sleep duration. During convulsions caused by pentylenetetrazole, a pronounced anticonvulsant effect of meldonium has been established. In turn, when using an alpha 2-adrenergic blocker, yohimbine at a dose of 2 mg/kg and the nitric oxide synthase (SOA) inhibitor N-(G)-nitro-L-arginine at a dose of 10 mg/kg before meldonium therapy, the anticonvulsant is completely blocked action of meldonium.

Overdose of meldonium may increase the cardiotoxicity caused by cyclophosphamide.

Carnitine deficiency resulting from the use of D-carnitine (a pharmacologically inactive isomer)-meldonium may increase the cardiotoxicity caused by ifosfamide.

Meldonium has a protective effect against indinavir-induced cardiotoxicity and efavirenz-induced neurotoxicity.

Special instructions

Patients with chronic liver and kidney diseases should use caution during long-term use (liver and/or kidney functions should be monitored).

Features of the effect of the drug on the ability to drivevehicle or potentially dangerous machinery

There is no data on the effect on the ability to drive a vehicle or operate potentially dangerous machinery.

Overdose

Cases of overdose are unknown, the drug is low-toxic and does not cause side effects dangerous to the patient's health.

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.

Due to the pronounced binding of the drug to proteins, hemodialysis is not essential.

Release form and packaging

5 ml in a colorless glass ampoule, hydrolytic class I with a line or break point.

5 ampoules are placed in a blister pack made of polyvinyl chloride film.

2 or 4 blister packs together with instructions for medical use in the state and Russian languages ​​are placed in a cardboard box.

Storage conditions

Store at a temperature not exceeding 25 °C.

Do not freeze!

Keep out of the reach of children!

Shelf life

Do not use after the expiration date stated on the package.

Conditions for dispensing from pharmacies

By prescription

Registration Certificate Holder

JSC "Grindeks" St. Krustpils 53, Riga, LV-1057, Latvia

Manufacturer

JSC "Sanitas" St. Veiveru 134B, Kaunas, LT- 46352, Lithuania

Address of the organization accepting claims in the territory of the Republic of Kazakhstan from consumers on product quality

Representative office of JSC "Grindeks"

050010, Almaty, Dostyk Ave., corner of st. Bogenbay Batyr, 34a/87a, office No. 1

t./f. 291-88-77, 291-13-84

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Mildronate, injections of which are prescribed to many patients, is a Latvian-made drug. It is effective in the treatment of chronic diseases of the heart, blood vessels, respiratory and nervous systems, and pathologies of the organs of vision. It speeds up the rehabilitation of patients with brain diseases, restores the tone of the central nervous system, and also reduces coordination disorders and normalizes motor reflexes. The medication normalizes the imbalance of somatic and vegetative processes in alcoholics and relieves withdrawal symptoms. The medicine adapts to extreme loads and quickly restores energy.

Mildronate solution for injection is a clear, colorless liquid in 500 mg/5 ml ampoules. The cardboard packaging contains two blisters of five ampoules.

The product is produced in syrup and capsule format. The medicine contains meldonium dihydrate and the auxiliary component sterile water for injection.

Pharmacological properties

A medicine with a non-proprietary international name Meldonium blocks the production of carnitine, improves metabolism and energy supply to cells, dilates blood vessels, and effectively saturates tissues in a state of hypoxia with blood and oxygen.

Mildronate is a synthesized analogue of gamma-butyrobetaine with a proven broad therapeutic effect.

1. Antianginal effect prevents angina attacks.
2. The cardioprotective effect improves the activity of the heart muscle.
3. Antihypoxic property prevents oxygen starvation of cells.
4. Angioprotective qualities strengthen the walls of blood vessels and optimize blood microcirculation.

Injections of the drug Mildronate are prescribed when the patient needs:

• restore performance and increase endurance;
• improve intellectual productivity;
• relieve symptoms of VSD, psychosomatic and physical stress;
• improve the immunity of tissues and humoral fluids (blood and lymph);
• protect the heart muscle.

Mildronate, a cardioprotector, activates the metabolism of damaged myocardium during an attack of acute ischemia:

• inhibits necrotic processes;
• shortens the recovery period;
• restores the cellular balance of oxygen metabolism;
• provides transport of adenosine triphosphoric acid;
• reduces the concentration of carnitine to enhance the synthesis of the vasodilator gamma-butyrobetaine.

Indicators of heart failure after injections significantly improve. The patient has the following clinical picture:

• attacks of angina and anginal pain occur less frequently;
• myocardial contractility is normalized, cardiac output increases;
• load tolerance increases.

From the effects of Mildronate, the ischemic zone in acute pathological conditions of the brain becomes a priority, and blood circulation increases in the damaged areas.

Why are intramuscular and intravenous injections prescribed?

Injections are preferred to tablets, taking into account the disease and severity of symptoms, the personal opinion of the doctor or patient. IV or IM injections are prescribed when maximum and rapid improvement in a person’s physical capabilities is expected. Then treatment continues with Meldonium capsules.

When a quick effect is required, intravenous injections are carried out in a jet manner. If the immediate effect of the drug on the patient is not intended, the solution is injected into a vein by infusion using a dropper. The drug is administered intramuscularly during the chronic course of the disease, when there are no acute conditions.

Instructions for use of Mildronate injections

To eliminate excessive agitation and insomnia, Mildronate is administered shortly before bedtime. The drug is prescribed for administration by the following methods: intramuscularly (IM), intravenously (IV) and parabulbar (into the lower eyelid area when treating the visual organs).

The concentration of the substance in plasma reaches a maximum within a few minutes after parenteral administration. The biological availability of the drug is one hundred percent.

Dosage for various pathologies

The area of ​​injection, the intensity of the course, the volume of doses and the choice of complementary drugs are determined by the doctor, based on data on the patient’s condition, taking into account the indications for use of the drug and the expected purpose.

1. Vascular and heart diseases:

• intravenous injections in a stream of 5-10 ml once a day (or twice, 0.5 doses);
• IM 5 ml 1-2 times a day.

The average course of treatment is about 14 days, then capsules are prescribed. The total treatment period is 4-6 weeks.

2. Impaired brain activity and blood circulation:

• for acute conditions: intravenous injection 5 ml 1 r./day. - 10 days, then capsules of 0.5-1 g; general course 4-6 weeks;
• for chronic diseases: IM or IV injection 5 ml 1 r./day. 10 days, continuation of treatment orally 0.5 g; general course – 4-6 weeks.

A repeated course is carried out after consultation and recommendation of a doctor two to three times a year.

3. Treatment of eye pathologies: parabulbar 0.5 ml – 10 days.

4. Elimination of the influence of overloads, increasing the endurance threshold: IM or IV 5 ml 1 time per day, 10-14 days. If necessary, the course is repeated after 2-3 weeks.

5. Treatment of the consequences of chronic alcoholism: IM or IV 5 ml 2 times a day. The course of treatment is 7-10 days.

Application in sports

Meldonium course accelerates metabolic processes. Muscle tissues strained by training regenerate faster.

The drug gives positive results in sports disciplines, but is especially effective for endurance athletes with aerobic exercise. It preserves cardiac tone and allows you to achieve high results in an environment with insufficient oxygen concentration.

Bodybuilders value Mildronate as a means to nourish muscles. During the period of injections, strength training becomes more effective. With high overloads in the body, the concentration of fatty acids - sources of energy - decreases and the athlete quickly gets tired. The drug expands the boundaries of physical capabilities. In addition, it does not allow harmful forms of unoxidized fatty acids to accumulate.

Mildronate has a wide range of effects. During sports activities, the valuable qualities of the medicine are confirmed by:

• performance jump;
• acceleration of psychosomatic processes;
• improving the functioning of the heart muscle;
• coping with stress during important competitions;
• return to previous physical shape after sports injuries;
• optimal delivery of glucose to cells, providing them with the necessary energy;
• strengthening metabolic processes and removing toxic breakdown products from the body;
• increasing speed and coordination of movements.

Mildronate promotes rational energy consumption and accumulates it in the body. Helps to reveal the athlete's potential under conditions of maximum stress, improves his performance.

It is important to use the drug when playing sports in the correct dosage. Optimal regimen: 1 mg of the drug per 1 kg of body weight – 1 r/day 30 minutes before the start of training.

Course of injections or capsules: from 6 weeks to 3 months. Then the inevitable addiction to the drug begins, so they take a four-week break. The maximum daily oral intake is 2 grams. It is believed that Mildronate injections intramuscularly are twice as effective as tablets. To improve the quality of the effect, a useful combination with riboxin or L-carnitine is recommended.

In 2016, Mildronate was recognized as a doping agent. The fact of using the drug leads to the disqualification of the athlete. The half-life of Meldonium and metabolites through the kidneys is about 5 hours. How long it takes for the substance to completely leave the tissues after completing the course has not yet been established.

Contraindications, side effects, overdose

Meldonium is not approved for use when the patient:

• increased intracranial pressure;
• internal tumors were detected;
• venous outflow is impaired;
• age has not reached the age of majority;
• Excessive sensitivity to the components of the product was diagnosed.

In case of kidney and liver diseases, especially chronic ones, injections are carried out with caution.

It has been established that the substance is able to penetrate the hematoplacental barrier. Safety of use during pregnancy has not been officially confirmed. To absolutely exclude a negative effect on the formation and vital activity of the fetus, it is better to postpone injections.

There is no data on the ability of Meldonium to concentrate in breast milk. If there are indications for injections during lactation, you should not put the baby to the breast.

The manufacturer did not provide information about the undesirable effect of the drug on the driver’s ability to adequately drive a car.

A drug overdose is diagnosed when characteristic signs appear:

• a sharp decrease in blood pressure combined with severe headache;
• rapid heartbeat and sudden weakness.

Negative side effects occur infrequently. Manifestations of allergies (itching and redness of the skin, urticaria, angioedema), tachycardia, changes in blood pressure, and increased nervous excitability are observed. Changes in the blood count (increased levels of eosinophils) and general weakness are extremely rare.

Interaction with other drugs

The combinatorial properties of Mildronate and other drugs were established during special clinical studies.

It turned out that injections of the drug enhance the effect of cardiac glycosides, coronary dilation drugs, and drugs for lowering blood pressure.

Meldonium can be combined with drugs from the following pharmacological groups:

• anticoagulants;
• antiplatelet agents;
• diuretics;
• bronchodilators;
• antianginal drugs;
• antiarrhythmic drugs;
• long-acting nitrates.

To control the decrease in blood pressure, nitroglycerin and antihypertensive drugs are used with caution.

Analogues of Mildronate in injections

With varying degrees of success, solutions with similar therapeutic effects can replace Meldonium:

• Midolat;
• Cardionate;
• Meldonium organics;
• Idrinol.

Mildronate injections are often prescribed by a neurologist, therapist or cardiologist. Injections are recommended to improve cardiac activity, increase endurance, and strengthen general tone. Patients feel better after the first course of use.

Whether the drug is needed or not - this decision requires the advice of a qualified specialist. Only a doctor will determine how much a course of injections is necessary. You can only entrust the selection of the optimal treatment regimen to a professional.

Thanks to its mechanism, it is used in the treatment of diseases of the heart and blood vessels, to increase the body's endurance. Reviews from patients who took the drug say that it improves physical and mental condition during overload and the rehabilitation period.

A drug that can improve and enhance metabolic processes operating in the tissues of the body. This new generation metabolic agent is used primarily as an ischemic drug.

It was observed that long-term treatment with the drug reduces the development of angina pectoris. The active substance of the drug, meldonium, also affects the central nervous system, improving cognitive functions and mental activity.

For what disorders is the drug prescribed:

1.Cardiology:

• coronary heart disease;
• stable angina pectoris;
• heart failure;
• menopausal cardiomyopathy;
• prevention of myocardial infarction.

2.Neurology:

• cerebral and cardiac ischemia;
• consequences of cerebrovascular accidents.

3. Ophthalmology:

• pathological changes in the fundus;
• retinopathy;
• impaired blood circulation in the retinal area.

4. Pulmonology:

• obstructive changes in the lungs.

5. Narcology:

• relieving symptoms of chronic alcoholism.

6. General practice:

• nervous fatigue;
• low performance;
• asthenia not associated with exercise;
• overload in athletes.

The drug is not used as the main medicine for diseases, but as an adjunct to treatment.

Compound

Mildronate (reviews from patients who took the drug indicate improved well-being) contains the active ingredient meldonium, which is an analogue of y-butyrobetaine, a precursor of levocarnitine, which is found in every cell of the human body.

One capsule of the drug contains:

• Meldonium digidratum as active ingredient, 250 mg;
• dried starch extracted from potatoes as a leavening agent;
• silicon oxide (absorbent);
• calcium salt and stearic acid, as an auxiliary component.

Capsule composition:

• titanium dioxide as a filler;
• gelatin as a source of collagen.

In what form is it produced?

The drug is available in two dosage forms - gelatin shell and ampoules. The white capsule contains a crystalline hygroscopic powder with a slight odor. Capsules are packaged in 10 pcs. in blister packs, blister packs. The cardboard box contains 4 cells and includes instructions for use. Cost – from 300 rubles.

The liquid form is available in ampoules, each of which contains 5 ml of the drug, intended for intravenous injection. One ml of the drug contains 100 mg of the active substance, meldonium. The cost of a package of 10 ampoules is from 300 rubles.

Pharmacodynamics

The main effect of the drug is the restoration of foci of impaired blood circulation in certain areas of tissue where the accumulation of unwanted amino acid - carnitine. Mildronate, while maintaining the rate of metabolic processes, reduces the level of carnitine, suppressing its biosynthesis and absorption in the kidneys.

Levocarnitine is involved in the oxidation of fatty acids, reducing their rate, which are the main source of energy for the myocardium. Carnitine is also involved in the transport of acids across the mitochondrial membrane.

Due to a decrease in the oxidation of fatty acids in mitochondria, cells switch to a glycolytic source, which forces the heart muscle to use oxygen in an increased manner. In addition, meldonium enhances the ability of red blood cells to release oxygen.

Meldonium reduces the concentration of glucose in the blood, has a cardioprotective effect, and weakens the development of atherosclerosis. The drug continuously trains the heart, thereby preparing cellular metabolism and membrane structures for survival under conditions of ischemic stress, if it occurs.

The drug has a vasodilating effect due to the production of nitric oxide in the endothelium (cellular inner surface) of blood vessels.

The active substance, meldonium dihydrate, has an effect on the body:

In heart failure, Meldonium digidratum increases myocardial contractility and reduces the frequency of angina attacks.

Pharmacokinetics

After taking the drug, Meldonium digidratum is quickly absorbed, its bioavailability is 78%. Bioavailability in the systemic circulation, or maximum concentration is achieved 1–2 hours after oral administration.

The synthesis and breakdown of the substance occurs in the liver, with the formation of two metabolites. Excreted through the kidneys, the half-life depends on the dose, but not more than 6 hours. Trace concentrations remain in the body for a long time.

Application

Mildronate (reviews from patients who took the drug are mostly positive) improves metabolism in the muscle cells of the heart and supports energy supply to all organs. Like any medicine, meldonium should be taken on the recommendation of a doctor, taking into account the existing symptoms, age, and characteristics of the patient’s body.

For children under 18 years old

Since no medical studies have been conducted on the use of the drug in childhood, it is prohibited to prescribe it under 18 years of age.

For adults

Mildronate for adults is recommended in the following doses - 500 mg or 2 capsules. Taken in one dose, in the morning, or divided into two doses of 250 mg, morning and afternoon. Since the drug has a tonic effect, taking it in the evenings is not recommended. The course of treatment is no more than 14 days. If necessary, you can continue taking it after a 2-3 week break.

In case of circulatory disorders in the brain, the dose can be increased to 1 g, which is taken in one or two doses. Treatment lasts from 4 to 6 weeks. People engaged in energy-intensive mental activities are prescribed 4 tablets. per day (500 mg) for 2 weeks.

In complex therapy to relieve withdrawal symptoms, a 10-day treatment is carried out, 4 capsules per day.

Mildronate in ampoules is used intramuscularly, intravenously and for eye injections. The medicine does not require additional dilution with saline solutions. Intravenous infusions are carried out more often, and intramuscular injections are made during the absence of acute conditions of the disease.

For pregnant women

Clinical trials of the drug on the effects of the female body during pregnancy and breastfeeding have not been carried out, which makes its use impossible during these periods.

For the elderly

Elderly people should use the drug with caution. Since many people aged 60+ have chronic diseases, kidney and liver, the use of the drug should be agreed with the attending physician.

Contraindications

Mildronate is contraindicated in people who have hypersensitivity to one of the components of the drug. Reviews from patients indicate that some people taking the drug experienced skin redness that quickly disappeared.

The drug is contraindicated in people with hypertension due to:

• impaired venous outflow;
• intracranial hematoma.

People with reduced kidney and liver function should use the medicine with caution and should first consult with their doctor. Does meldonium have an effect on the ability to drive a vehicle, does it increase the speed of psychomotor reactions - these aspects have not been studied and there is no data available. It is not advisable to combine the drug with alcohol.

Overdose

Cases of overdose have not been reported because the drug is low-toxic and does not cause severe reactions.

After injections, in case of increased volume of medication, symptoms may occur:

• decreased blood pressure;
• headaches;
• increased heart rate;
• general weakness.

In such cases, symptomatic treatment is carried out. Doctors advise monitoring the functioning of the kidneys and liver, but hemodialysis is ineffective because the medicine has a high level of binding to blood proteins.

Side effects

Mildronate (reviews from patients who took the drug contain information about side effects) is usually well tolerated. However, in susceptible people and those who have exceeded doses, secondary reactions may occur.

Body systems	Types of reactions	Response frequency
Lymphatic system and hematopoietic	Eosinophilia (increased number of eosinophils in the blood)	rarely
Immune system	Allergies (skin redness, itching, swelling)		often
Cardiac system	Tachycardia, arrhythmia, hypertensive crisis	rarely
Vascular system	Decreased blood pressure	rarely
Nervous system	Headache		often
	overexcitement	rarely
General violation	General weakness	rarely
Musculoskeletal system	Muscle weakness, spasms	rarely
Urinary system	Frequent urination	rarely

When taking the drug, you should remember that it may affect the results of some laboratory and instrumental studies:

• increase the concentration of c-reactive protein in the blood;
• increase eosinophils in the blood;
• increase triglyceride and cholesterol levels;
• accelerate sinus rhythm at the time of ECG.

If a doping control is carried out, the drug gives a positive result, which should be taken into account by people participating in competitions.

Drug interactions

Mildronate (reviews of patients who took the drug can be found on medical websites) is used with the following drugs:

• prolonged action (having a long-lasting therapeutic effect);
• antianginal agents (increasing blood flow to the heart);
• diuretics;
• glycosides (herbal preparations used to treat heart failure).

The drug can be combined with medications that affect blood microcirculation:

• reducing blood clotting activity;
• affecting heart rhythm disturbances;
• preventing thrombus formation.

Meldonium enhances the effect of antihypertensive drugs and vasodilators:

• nitroglycerin;
• beta blockers;
• nifedipine;
• nitrates;
• calcium channel antagonists.

It is undesirable to use meldonium simultaneously with these drugs, since tachycardia and hypotension may develop. It is also capable of enhancing the effects of drugs that expand the lumen of peripheral and coronary vessels and lower blood pressure.

Storage conditions and periods

The drug must be stored in a dry place, protected from children. The temperature should not exceed +25°C. Shelf life – no more than 4 years.

Conditions for dispensing from pharmacies

The drug is over-the-counter and available for free sale.

Analogs

The following medications can be used to treat diseases for which Mildronate is used:

Name	Action	Who is it recommended for?	How to take
Preductal	Improves metabolic changes in the myocardium under conditions of ischemia,	Prescribed for the prophylactic purpose of angina attacks in case of long-term therapy of coronary heart disease.	Recommended dose: 1 tablet. 2 times a day along with meals
Akgovegin	Activates cellular metabolism, increasing the transport of glucose and oxygen	Prescribed in case of insufficient cerebral circulation, trophic disorders	1-2 tablets three times a day before meals
Riboxin	Participates in glucose metabolism, stimulates metabolic processes that develop with a lack of ATP	Prescribed as part of complex therapy for angina pectoris, inflammation, primary myocardial damage, and alcoholic liver damage.	The drug is taken after meals, 200 mg three times a day, for 2 months.
Mexidol	Restores cerebral blood supply in case of vegetative-vascular dystonia	Intended for patients with cerebrovascular accidents, vegetative-vascular dystonia, and anxiety disorders caused by neuroses.	The main dose is 250 mg twice a day, no more than 2 weeks.
Piracetam	Improves memory, attention, performance, restores brain function after intoxication	Used to treat balance disorders and memory loss.	Taken on an empty stomach, the daily dose can be divided into two doses, the last dose is taken no later than 17 hours
Sodium adenosine triphosphate	The drug improves metabolism and energy supply to body tissues	Used to relieve attacks of paroxysmal supraventricular tachycardia.	Administered intravenously under ECG and blood pressure monitoring
Preparations with the active ingredient meldonium
Melfort		For symptoms of chronic heart failure, circulatory disorders in the brain, and for relieving symptoms of alcohol syndrome.	For the first 10 days, an injection solution is prescribed, and then 2 capsules (500 mg) per day are prescribed once. Course – 5–6 weeks
Vasomag	Affects metabolism, reduces symptoms of psychophysical stress	It is used as a single drug, as part of complex therapy in case of cerebrovascular accident, chronic heart failure, and decreased mental performance.	In the first 10 days it is administered intramuscularly, and then 2 capsules per day are prescribed.
Medatern	Antioxidant, metabolic agent	It is used in neurology, for hemorrhagic stroke, chronic circulatory failure in the brain, and decreased performance.	Prescribed 1 capsule 3 times a day for 4–5 days. Then the dose is increased, the course of treatment is up to 6 weeks.
Cardionate	Metabolic agent	For ischemic disease, as part of complex therapy for cerebral circulatory disorders, circulatory disorders in the retina.	For complex therapy, 500–1000 mg is used 1 or 2 times a day, treatment is carried out for up to 40 days

The table shows approximate doses of drugs. They vary depending on the disease and the patient’s condition. Medicines and analogues are selected as prescribed by a doctor, since many side effects are possible.

Mildronate has a lot of good reviews. Patients who took the drug correctly indicate a pronounced positive effect in the prevention of ischemic diseases.

Video about the drug Mildronate

The mechanism of action of the drug Mildronate:

Metabolic drug

Active ingredient

Release form, composition and packaging

Solution for IM, IV and parabulbar administration transparent, colorless.

Excipients: water for injection.

5 ml - colorless glass ampoules (5) - plastic cell packaging (2) - cardboard packs.
5 ml - colorless glass ampoules (5) - plastic cell packaging (4) - cardboard packs.

Pharmacological action

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

Under conditions of increased stress, 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; also 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 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, Mildronate improves blood circulation in the ischemic area and promotes blood redistribution in favor of the ischemic area.

The drug eliminates functional disorders of the nervous system in patients with chronic alcoholism with withdrawal syndrome.

Pharmacokinetics

Suction and distribution

The bioavailability of the drug after intravenous administration is 100%. Cmax in the blood is reached immediately after its administration.

Metabolism and excretion

Metabolized in the body to form two main metabolites, which are excreted by the kidneys. T 1/2 is 3-6 hours.

Indications

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

— chronic failure;

— dishormonal cardiomyopathy;

— in the complex treatment of acute and chronic disorders of the blood supply to the brain (stroke and cerebrovascular insufficiency);

- hemophthalmos and retinal hemorrhages of various etiologies;

- thrombosis of the central retinal vein and its branches;

- retinopathy of various etiologies (diabetic, hypertensive);

- reduced performance;

— mental and physical overstrain (including among athletes);

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

Contraindications

- increased intracranial pressure (in case of impaired venous outflow, intracranial tumors);

- age under 18 years (efficacy and safety have not been established);

- pregnancy;

- period of breastfeeding;

- hypersensitivity to the components of the drug.

With caution: for liver and/or kidney diseases.

Dosage

Due to the possible development of an stimulating effect, it is recommended to use it in the first half of the day.

Mildronate is prescribed intramuscularly, intravenously and parabulbarly. The method of administration, dose and duration of treatment are determined individually, depending on the indications, severity of the condition and other factors.

At IHD (myocardial infarction) as part of complex therapy, the drug is prescribed intravenously in a dose of 0.5-1.0 g/day (5-10 ml of Mildronate), using the entire dose at once or dividing it into 2 administrations.

At IHD (stable angina), chronic heart failure and dyshormonal cardiomyopathy as part of complex therapy, the drug is prescribed intravenously in a bolus of 0.5-1.0 g/day (5-10 ml of the drug Mildronate), applying the entire dose at once or dividing it into 2 injections, or intramuscularly at 0.5 g 1-2 times/day , the course of treatment is 10-14 days, followed by a transition to taking the drug orally. The general course of treatment is 4-6 weeks.

As part of complex therapy cerebrovascular accidents in the acute phase the drug is prescribed at 0:5 g (5 ml of Mildronate) 1 time/day IV for 10 days, followed by switching to oral administration at 0.5-1 g. The general course of treatment is 4-6 weeks.

At chronic cerebral circulatory failure (dyscirculatory encephalopathy) Prescribe 0.5 g (5 ml of the drug Mildronate) IM or IV 1 time/day for 10 days, then 0.5 g orally. The general course of treatment is 4-6 weeks. Repeated courses (usually 2-3 times a year) are possible after consultation with a doctor.

At hemophthalmia and retinal hemorrhages of various etiologies, thrombosis of the central retinal vein and its branches, retinopathy of various etiologies (diabetic, hypertensive) Prescribe 0.05 g (0.5 ml of the drug Mildronate) parabulbarly for 10 days. The drug is used as part of combination therapy.

At mental and physical stress the drug is administered 0.5 g (5 ml of the drug Mildronate) IM or IV 1 time/day. The course of treatment is 10-14 days. If necessary, treatment is repeated after 2-3 weeks.

At chronic alcoholism Prescribe 0.5 g (5 ml of the drug Mildronate) IM or IV 2 times a day. The course of treatment is 7-10 days.

Side effects

Depending on the frequency of occurrence, the following groups of undesirable side reactions according to WHO are distinguished: very often (>1/10), often (>1/100,<1/10), нечасто (>1/1000, <1/100), редко (>1/10,000 and<1/1000), очень редко (<1/10 000), частота неизвестна (по имеющимся данным частоту оценить невозможно).

Allergic reactions: rarely - redness, rash, itching, swelling.

From the cardiovascular system: rarely - tachycardia, decreased or increased blood pressure.

From the digestive system: rarely - dyspeptic symptoms.

Other: rarely - excitement; very rarely - eosinophilia, general weakness.

Overdose

Mildronate is low-toxic and does not cause side effects dangerous to the health of patients.

Symptoms: decreased blood pressure, accompanied by headache, tachycardia, dizziness and general weakness.

Treatment: carrying out symptomatic therapy.

Drug interactions

Mildronate can be combined with antianginal agents, antiplatelet agents, antiarrhythmic agents, diuretics, and bronchodilators.

The drug enhances the effect of cardiac glycosides.

Due to the possible development of moderate tachycardia and arterial hypotension, caution should be exercised when combined with nifedipine, alpha-blockers, other antihypertensive drugs and peripheral vasodilators, because Mildronate enhances their effect.

Special instructions

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 and its use is not urgently necessary.

Since January 1, 2016, meldonium has been included in the list of prohibited substances of the World Anti-Doping Agency.

Impact on the ability to drive vehicles and machinery

There is no data on the adverse effects of the drug Mildronate on the speed of psychomotor reaction.

Pregnancy and lactation

The safety of use in pregnant women has not been studied, therefore, in order to avoid possible adverse effects on the fetus, its use is contraindicated.

The excretion of the drug Mildronate in breast milk and its effect on the health of the newborn have not been studied. If it is necessary to use the drug during lactation, breastfeeding should be stopped.

Storage conditions and periods

The drug should be stored out of the reach of children at a temperature not exceeding 25°C; do not freeze. Shelf life - 5 years. Do not use after the expiration date stated on the package.

Mildronate is a drug designed to improve metabolism in cells. Indicated for athletes to increase endurance and training efficiency. It is also used to treat heart disease and detoxify the body from alcohol addiction.

Indications for use

All forms of release are intended for the treatment of diseases in adults:

• Coronary disease is damage to the myocardium of the heart.
• Heart failure is a dysfunction of the myocardium.
• Overtraining syndrome in athletes is the appearance of pain that does not go away after resting and fatigue.
• Increased mental stress, decreased concentration and memory.
• Hangover syndrome is the appearance of symptoms of alcohol withdrawal.
• Dysfunction of cerebral circulation.
• Decreased performance, chronic fatigue syndrome;
• Hemophthalmos is the penetration of blood or the formation of blood clots into the vitreous body of the eye.
• Retinopathy is damage to the retina of the eye.

For diseases cardiovascular system this drug is used to treat used as an adjunct to primary therapy. It improves blood circulation and normalizes myocardial contractility.

Over the course of several Athletes are recommended to use Mildronate for weeks to increase physical strength, improve metabolism. This happens due to the fact that the composition contains Meldonium, which is a synthesized analogue of gamma-butyrobetaine (a substance present in cells).

Pharmacodynamics and pharmacokinetics

The main substance of this medicine is meldonium dihydrate. It was synthesized about half a century ago in Latvia.

Initially, the drug was prescribed to the military, in particular, to eliminate drowsiness and syndrome

chronic fatigue. But later, scientists established the positive properties of Mildronate for the functioning of the cardiovascular system and the body as a whole.

The active substance acts in a complex manner. It restores the balance between the cells' needs for

oxygen and its delivery, removes accumulated toxins and the consequences of their effects on the body.

As a result of the use of Mildronate, the body increases endurance to physical and

Other pharmacodynamic properties of the drug include:

• normalization of cerebral circulation;
• improvement of blood circulation in the area of ​​ischemia;
• slowing down the formation of the necrotic zone;
• elimination of functional disorders of the nervous system;
• reduction of the rehabilitation period in the treatment of heart disease, stroke and alcoholism.

After oral administration, Mildronate is rapidly absorbed from the gastrointestinal tract. Excreted in urine after 3-6 hours.

Compound

The composition of the medicine depends on the form of release. Intravenous ampoules contain two substances:

• meldonium;
• water for injections.

Oral capsules contain more substances:

• meldonium;
• potato starch;
• calcium stearate;
• colloidal silicon dioxide;
• titanium dioxide and gelatin in the shell.

Mildronate syrup includes:

• meldonium;
• purified water;
• cherry essence;
• glycerol;
• dyes;
• propylene glycol.

Release form

Mildronate is available in three forms:

1. Capsules. Sometimes they are mistakenly called tablets, but this concept is not correct. The tablet form of this drug is not available. Capsules come in two types: with 250 mg and 500 mg of active substance. Sold in cardboard packaging containing 40 and 60 pieces.
2. Syrup. Sold in two types: 150 ml and 250 ml. 5 ml (one dose) of the medicine contains 250 mg of the active substance. Available in cardboard packaging. Includes a 5 ml measuring spoon.
3. Ampoules. One ampoule contains 5 ml of the drug, which contains 250 mg of the active substance. Available in cardboard packaging of 10 ampoules.

The variety of forms of the drug allows you to choose the most convenient method of use for yourself.

Mildronate, produced in ampoules, has the fastest absorption. The solution is injected into a muscle or vein and reaches its maximum concentration in the blood immediately after administration. In second place in terms of absorption rate is syrup. But it is more convenient to take capsules with water.

Pharmacological action

The drug has several pharmacological actions:

• angioprotective – dilation of blood vessels, reduction of tissue edema, stimulation of metabolism in cells, restoration of blood composition;
• cardioprotective – strengthening the heart muscle, accelerating cell regeneration processes, reducing the concentration of toxins in the body;
• antihypoxic – reducing tissue oxygen demand, activating cellular metabolism, stimulating the regeneration process, improving tissue nutrition;
• antianginal – prevention and relief of angina attacks, oxygen delivery to the myocardium.

As a result of its complex effect on the body, the drug shows high efficiency. Athletes who need additional stimulation of metabolism note particular benefits.

Directions for use and doses

Before starting treatment, you should study mildronate instructions for use and recommendations.

manufacturer. But only a doctor can prescribe the drug and select the dosage. You cannot take Mildronate on your own.

Dosage and rules of use depend on the form of the medicine.

Capsules

The drug has a tonic and stimulating effect, so it is recommended to take it

in the morning. Athletes can use it 1-2 hours before physical activity.

The dosage depends on the purpose of use:

• For the treatment of cardiovascular diseases in complex therapy, the dosage is 0.5-1 grams per day. 250 mg capsules are taken up to 4 per day, 500 mg tablets - up to 2 per day. The daily dose should be divided into 1-2 doses. The duration of treatment should not exceed 6 weeks.
• For the treatment of chronic dysfunctions of cerebral circulation, the dosage is the same. During the year you can take 2 courses lasting no more than 6 weeks each.
• For the treatment of chronic alcoholism and detoxification, the dosage is 500 mg 4 times a day. The duration of therapy reaches 10 days.
• To increase endurance and physical strength, athletes need to take the drug 1-2 capsules twice a day before training. Duration of treatment is 21 days, during competitions – up to 14 days.

Capsules are washed down with water for ease of swallowing.

Syrup

One portion of the medicine is 5 ml (1 scoop). For the treatment of heart disease and when it worsens

for cerebral circulation, you need to take 1 scoop of syrup twice a day.

The dosage for athletes is selected individually. Daily norm – 1 gram (4 scoops),

divided into two doses.

Ampoules

The solution, produced in ampoules, is administered in three ways:

• intravenously;
• intramuscularly;
• parabulbar (eye prick).

Dosage:

• For pathologies of the heart and brain, the drug is injected into a vein, 2 ampoules per day. The dosage is divided into 2 doses. The course of therapy lasts from 4 to 6 weeks.
• For chronic alcoholism, the dosage is 1 gram per day for 10 days. It can be administered intravenously or intramuscularly.
• Athletes need to administer 500 mg intravenously once. The duration of treatment should not exceed 3 weeks.
• To treat diseases of the retina, the drug is administered by eye injection of 0.5 ml of solution per day. Duration of therapy is 10 days.

For athletes

The main advantage of Mildronate is its ability to improve metabolism in cells. This leads to accelerated elimination

from organisms of free radicals and breakdown products. The drug can be safely called an antioxidant, which improves well-being, slows down the aging process of cells and helps rapid muscle recovery.

The components included in the composition eliminate the symptoms of overtraining and help fight physical fatigue. This has a beneficial effect on the general condition of the athlete and his personal performance.

The product is most effective during heavy physical activity and active training. It is recommended to take the drug

in situations where the body does not have time to rest between workouts. For example, when preparing for competitions. However, Mildronate is not a prohibited doping drug.

You can take the drug for no more than 6 weeks without a break. Longer use causes addiction, that is, the body stops responding to the incoming substances.

But Mildronate alone is not enough to increase the effectiveness of training and endurance of the body. It only works in

complex with proper nutrition and a rational daily routine, when rest alternates with hard work.