Mildronate^® (Capsules, Solution) Instructions for Use

ATC Code

C01EB22 (Meldonium)

Active Substance

Meldonium (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Metabolic drug

Pharmacotherapeutic Group

Metabolic agent

Pharmacological Action

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

Under conditions of increased load, Mildronate^® restores the balance between the delivery and demand of cells for oxygen, eliminates the accumulation of toxic metabolites in cells, protecting them from damage; it also has a tonic effect. As a result of its use, the body acquires the ability to withstand load and quickly restore energy reserves. Due to these properties, Mildronate^® is used to treat various disorders of the cardiovascular system, cerebral blood supply, and also to increase physical and mental performance. As a result of the decrease in carnitine concentration, gamma-butyrobetaine, which has vasodilating properties, is intensively synthesized.

In case of acute ischemic myocardial damage, Mildronate^® slows down the formation of the necrotic zone and shortens the rehabilitation period. In heart failure, it increases myocardial contractility, increases tolerance to physical activity, and reduces the frequency of angina attacks.

In acute and chronic ischemic cerebrovascular accidents, Mildronate^® improves blood circulation in the ischemic focus and promotes the redistribution of blood in favor of the ischemic area.

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

Pharmacokinetics

Absorption and Distribution

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

Metabolism and Excretion

It is metabolized in the body with the formation of two main metabolites, which are excreted by the kidneys. T_1/2 is 3-6 hours.

Indications

• In the complex therapy of coronary artery disease (angina pectoris, myocardial infarction);
• Chronic heart failure;
• Dishormonal cardiomyopathy;
• In the complex therapy of acute and chronic cerebrovascular accidents (stroke and cerebrovascular insufficiency);
• Hemophthalmos and retinal hemorrhages of various etiologies;
• Thrombosis of the central retinal vein and its branches;
• Retinopathies of various etiologies (diabetic, hypertensive);
• Reduced performance;
• Mental and physical overstrain (including in athletes);
• Withdrawal syndrome in chronic alcoholism (in combination with specific therapy for alcoholism).

ICD codes

Dosage Regimen

Capsules

Due to the possibility of developing a stimulating effect, the drug is recommended to be used in the first half of the day and no later than 5:00 PM when taken several times a day.

For coronary artery disease (angina pectoris, myocardial infarction), chronic heart failure as part of complex therapy, the drug is prescribed orally at a dose of 500 mg-1 g/day, frequency of administration 1-2 times/day. The course of treatment is 4-6 weeks.

For dishormonal cardiomyopathy, Mildronate^® as part of complex therapy is prescribed orally at 500 mg/day. The course of treatment is 12 days.

For subacute cerebrovascular accidents (after stroke) after completion of the course of injection therapy with Mildronate^®, continue taking it as part of complex therapy orally at 500 mg-1 g/day, using the entire dose at once or dividing it into 2 doses. The course of treatment is 4-6 weeks. Repeated courses (usually 2-3 times a year) are possible after consultation with a doctor.

For chronic cerebrovascular accidents (cerebrovascular insufficiency) – as part of complex therapy orally at 500 mg/day. The general course of therapy is 4-6 weeks. Repeated courses are possible after consultation with a doctor (usually 2-3 times a year).

For reduced performance, mental and physical overstrain (including in athletes), it is prescribed orally at 500 mg 2 times/day. The course of treatment is 10-14 days. If necessary, therapy is repeated after 2-3 weeks.

Athletes are recommended to take 500 mg-1 g 2 times/day before training. The duration of the course in the preparatory training period is 14-21 days, during the competition period – 10-14 days.

For withdrawal syndrome in chronic alcoholism (in combination with specific therapy for alcoholism), the drug is prescribed orally at 500 mg 4 times/day. The course of treatment is 7-10 days.

Solution

Due to the possible development of a 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, doses and duration of the course of treatment are established individually, depending on the indications, severity of the condition and other factors.

For coronary artery disease (myocardial infarction) as part of complex therapy, the drug is prescribed intravenously as a bolus at 0.5-1.0 g/day (5-10 ml of Mildronate^®), using the entire dose at once or dividing it into 2 administrations.

For coronary artery disease (stable angina pectoris), chronic heart failure and dishormonal cardiomyopathy as part of complex therapy, the drug is prescribed intravenously as a bolus at 0.5-1.0 g/day (5-10 ml of Mildronate^®), using the entire dose at once or dividing it into 2 administrations, or intramuscularly at 0.5 g 1-2 times/day, course of treatment 10-14 days, followed by a switch to oral administration of the drug. The general course of treatment is 4-6 weeks.

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

For chronic cerebrovascular insufficiency (dyscirculatory encephalopathy), it is prescribed at 0.5 g (5 ml of Mildronate^®) intramuscularly or intravenously 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.

For hemophthalmos and retinal hemorrhages of various etiologies, thrombosis of the central retinal vein and its branches, retinopathy of various etiologies (diabetic, hypertensive), it is prescribed at 0.05 g (0.5 ml of Mildronate^®) parabulbarly for 10 days. It is also used as part of combination therapy.

For mental and physical overstrain, the drug is administered at 0.5 g (5 ml of Mildronate^®) intramuscularly or intravenously 1 time/day. The course of treatment is 10-14 days. If necessary, treatment is repeated after 2-3 weeks.

For chronic alcoholism, it is prescribed at 0.5 g (5 ml of Mildronate^®) intramuscularly or intravenously 2 times/day. The course of treatment is 7-10 days.

Adverse Reactions

Depending on the frequency of occurrence, the following groups of undesirable adverse reactions according to WHO are distinguished: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10,000 and <1/1000), very rare (<1/10,000), frequency unknown (cannot be estimated from the available data).

Allergic reactions rarely – redness, rash, itching, swelling.

From the cardiovascular system rarely – tachycardia, decrease or increase in blood pressure.

From the digestive system rarely – dyspeptic phenomena.

Other rarely – agitation; very rarely – eosinophilia, general weakness.

Contraindications

• Increased intracranial pressure (in case of impaired venous outflow, intracranial tumors);
• Age under 18 years (efficacy and safety have not been established);
• Pregnancy;
• Breastfeeding period;
• Hypersensitivity to the components of the drug.

With caution: in liver and/or kidney diseases.

Use in Pregnancy and Lactation

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

The excretion of Mildronate^® with 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 discontinued.

Use in Hepatic Impairment

The drug should be prescribed with caution in liver diseases.

Use in Renal Impairment

The drug should be prescribed with caution in kidney diseases.

Pediatric Use

Contraindicated in patients under 18 years of age, as efficacy and safety have not been established.

Special Precautions

Long-term experience in the treatment of acute myocardial infarction and unstable angina in cardiology departments shows that Mildronate^® is not a first-line drug for acute coronary syndrome and its use is not acutely necessary.

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

Influence on the ability to drive vehicles and mechanisms

There are no data on the adverse effect of Mildronate^® on the speed of psychomotor reactions.

Overdose

Mildronate^® is low-toxic and does not cause adverse reactions dangerous to the health of patients.

Symptoms decrease in blood pressure, accompanied by headache, tachycardia, dizziness and general weakness.

Treatment symptomatic therapy.

Drug Interactions

Mildronate^® can be combined with antianginal agents, anticoagulants, antiplatelet agents, antiarrhythmic agents, diuretics, 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 combining with nitroglycerin, nifedipine, alpha-blockers, other antihypertensive agents and peripheral vasodilators, as Mildronate^® enhances their effect.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F); do not freeze.

Shelf Life

The shelf life is 5 years. Do not use after the expiration date printed on the package.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.