Brainmax^® (Capsules, Solution) Instructions for Use

ATC Codes

C01EB (Other cardiac preparations)

N07XX (Other nervous system drugs)

Active Substances

Ethylmethylhydroxypyridine succinate (Grouping name)

Meldonium (Rec.INN registered by WHO)

Clinical-Pharmacological Group

A drug that improves tissue metabolism and energy supply, reducing tissue hypoxia

Pharmacotherapeutic Group

Antioxidant agent, metabolic agent

Pharmacological Action

A combined medicinal product, the action of which is due to the complex of its constituent components.

Pharmacodynamics

Meldonium (trimethylhydrazinium propionate) is a structural analogue of the precursor of carnitine – gamma-butyrobetaine, a substance that is present in every cell of the human body.

Under ischemic conditions, trimethylhydrazinium propionate restores the balance of oxygen delivery and consumption processes in cells, prevents disruption of ATP transport; simultaneously, it activates glycolysis, which proceeds without additional oxygen consumption.

Ethylmethylhydroxypyridine succinate by blocking the process of lipid peroxidation, reduces the number of free radicals, improves the structure and function of cell membranes, neurotransmitter transport and signal transmission in synapses.

The use of the complex of trimethylhydrazinium propionate and ethylmethylhydroxypyridine succinate leads to a synergistic pharmacodynamic interaction of the 2 components via conformationally selective agonism to receptors, which increases the neuroprotective activity of the drug. Under hypoxic conditions, the drug Brainmax^® leads to the activation of energy production in mitochondria, and under conditions of reduced blood supply, it helps to preserve the structure and viability of cells, in particular neurons and cardiomyocytes.

When using the drug Brainmax^®, the exerted antioxidant, antihypoxic, membrane- and stress-protective, anticonvulsant, anxiolytic, nootropic and anti-ischemic effects of the two active substances exceed the pharmacological effect of each of the components used separately, which leads to a reduction in the clinical manifestations of cerebrovascular insufficiency, an increase in the level of patient mobility, improvement of cognitive functions, improvement of memory and attention, normalization of emotional state, reduction of symptoms of mental and physical overstrain, increased performance, increased tolerance to mental and physical stress, improved blood supply to organs and tissues, cardioprotective action and improvement of neurological status.

The drug Brainmax^® under ischemic conditions slows down the formation of the necrotic zone and damage to myocardial cells, reduces platelet aggregation, promotes accelerated rehabilitation after cardiovascular events, supports the energy metabolism of the heart, which increases tolerance to physical activity and helps reduce the frequency of angina attacks in heart failure. It has a hypolipidemic effect, reduces the content of total cholesterol and LDL. Promotes detoxification and improves the state of the nervous system in alcoholism and withdrawal syndrome.

A clinical placebo-controlled study demonstrated the efficacy of the drug Brainmax^® for the treatment of patients with post-COVID asthenic syndrome and symptoms characteristic of conditions after a viral infection, such as asthenia, sleep disorders, headaches, dizziness, chronic fatigue syndrome, cognitive impairment, feeling of anxiety.

Pharmacokinetics

Meldonium

Absorption

After oral administration, it is rapidly absorbed from the gastrointestinal tract. Bioavailability is 78%. C_max in blood plasma is reached 1-2 hours after oral administration.

Metabolism

It is metabolized mainly in the liver with the formation of two main metabolites, which are excreted by the kidneys.

Excretion

T_1/2 after oral administration is 3-6 hours and depends on the dose. Trace concentrations of the drug persist in the body for a long time.

Ethylmethylhydroxypyridine succinate

Absorption and Distribution

Rapidly absorbed after oral administration. C_max at doses of 400-500 mg is 3.5-4.0 µg/ml. Rapidly distributed in organs and tissues. The mean residence time (MRT) of the drug in the body after oral administration is 4.9-5.2 hours.

Metabolism

It is metabolized in the liver by glucuronoconjugation. Five metabolites have been identified: 3-oxypyridine phosphate is formed in the liver and, with the participation of alkaline phosphatase, breaks down into phosphoric acid and 3-oxypyridine; the 2nd metabolite is pharmacologically active, formed in large quantities and detected in urine on days 1-2 after administration; the 3rd is excreted in large quantities in the urine; the 4th and 5th are glucuronoconjugates.

Excretion

T_1/2 after oral administration is 2.0-2.6 hours. It is rapidly excreted in the urine mainly as metabolites and in small amounts unchanged. It is most intensively excreted within the first 4 hours after taking the drug. The excretion parameters of the unchanged drug and metabolites in urine have individual variability.

Indications

• As part of complex therapy for cerebrovascular insufficiency;
• Mild cognitive impairments accompanied by manifestations such as memory impairment, distractibility, decreased ability to concentrate and learn, difficulties in assimilating new information;
• Reduced performance;
• Mental and physical overload (including in athletes, see “Special Precautions”);
• Asthenic conditions, including after a new coronavirus infection, accompanied by manifestations such as increased fatigue, sleep disorders, headaches, dizziness, emotional lability, cognitive impairment.

ICD codes

Dosage Regimen

Capsules

The drug is administered orally.

For complex therapy of cerebrovascular insufficiency, the drug Brainmax^® is taken 2 capsules (500 mg+500 mg) once a day. The course of treatment is 4 weeks. The daily dose can be increased to 2 capsules (500 mg+500 mg) 2 times a day as decided by the attending physician. The duration of administration can be increased as decided by the attending physician.

For mild cognitive impairments, reduced performance, asthenic conditions, mental and physical overloads – the daily dose of Brainmax^® for adults is 2 capsules (500 mg+500 mg). The daily dose is taken in one dose (2 capsules in the morning), or divided into 2 doses (1 capsule twice a day). The course of treatment is 10-14 days.

For asthenic conditions after a new coronavirus infection – the daily dose of Brainmax^® for adults is 4 capsules (1000 mg+1000 mg). Brainmax^® is taken as 2 capsules (500 mg+500 mg) twice a day. The course of treatment is 30 days.

Due to the possible development of a stimulating effect, it is recommended to take Brainmax^® in the first half of the day.

Solution

IM or IV.

A single dose is 250 mg + 250 mg or 500 mg + 500 mg.

The treatment regimen is established individually, depending on the indications and clinical situation.

Adverse Reactions

The frequency of side effects was determined in accordance with the WHO classification: very common (>10%); common (>1%, but <10%); uncommon (>0.1%, but <1%); rare (>0.01%, but <0.1%); very rare (<0.01%); frequency unknown (frequency cannot be determined from the available data).

Meldonium

From the hematopoietic system: frequency unknown – eosinophilia.

From the immune system: rare – allergic reactions (skin redness, skin rash, urticaria, itching, swelling, angioedema).

From the heart: very rare – tachycardia.

From the vascular system: rare – decrease or increase in blood pressure.

From the digestive system: common – dyspeptic symptoms.

From the nervous system: common – headache; frequency unknown – agitation.

General disorders: frequency unknown – general weakness.

Ethylmethylhydroxypyridine succinate

Immune system disorders: very rare – angioedema, urticaria.

Gastrointestinal disorders: very rare – dry mouth, nausea, pain, burning and discomfort in the epigastric region, heartburn, flatulence, diarrhea.

Nervous system disorders: very rare – headache.

Skin and subcutaneous tissue disorders: very rare – rash, itching, hyperemia.

Psychiatric disorders: very rare – drowsiness.

If the patient notices any other side effects not listed in the instructions, they should inform the doctor.

Contraindications

• Hypersensitivity to the components of the drug;
• Acute hepatic failure;
• Acute renal failure;
• Increased intracranial pressure (in case of impaired venous outflow and intracranial tumors);
• Pregnancy;
• Breastfeeding period;
• Children and adolescents under 18 years of age.

With caution

Chronic liver and kidney diseases, bronchial asthma.

Use in Pregnancy and Lactation

Brainmax^® is contraindicated during pregnancy and breastfeeding due to insufficient data on the efficacy and safety of the drug during these periods. Breastfeeding should be discontinued before starting the drug.

Use in Hepatic Impairment

Contraindicated in patients with acute hepatic failure.

Use with caution in the presence of chronic liver diseases.

Use in Renal Impairment

Contraindicated in patients with acute renal failure.

Use with caution in the presence of chronic kidney diseases.

Pediatric Use

The use of the drug is contraindicated in children and adolescents under 18 years of age (due to insufficient data on efficacy and safety).

Special Precautions

Meldonium can give a positive result in doping control. Since January 1, 2016, meldonium has been included in the list of prohibited substances by the World Anti-Doping Agency.

Patients with chronic liver and kidney diseases should exercise caution during long-term use of the drug.

There is insufficient data on the use of the drug in children and adolescents under 18 years of age.

If the patient’s condition does not improve or worsens after a course of therapy, the patient should consult a doctor. If long-term (more than a month) use of the drug is necessary, it is recommended to consult a specialist.

Effect on the ability to drive vehicles and mechanisms

During the period of taking the drug, caution should be exercised when working requiring increased concentration of attention and speed of psychomotor reactions (driving vehicles, mechanisms, etc.).

Overdose

The drug is low-toxic and does not cause severe adverse reactions.

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

Treatment: as a rule, the symptoms disappear on their own within a day. In case of severe manifestations, supportive and symptomatic treatment is carried out.

Drug Interactions

Meldonium

Enhances the effect of coronary dilating agents, some antihypertensive agents, cardiac glycosides. Can be combined with prolonged forms of nitrates, other antianginal agents, anticoagulants, antiplatelet agents, antiarrhythmic agents, diuretics, bronchodilators.

Due to the possible development of tachycardia and arterial hypotension, caution should be exercised when combining with nitroglycerin (for sublingual use) and antihypertensive agents (especially alpha-blockers and short-acting forms of nifedipine).

Simultaneous use of the drug with other drugs containing meldonium is not allowed, as it increases the risk of adverse reactions.

Ethylmethylhydroxypyridine succinate

Ethylmethylhydroxypyridine succinate is compatible with all drugs used to treat somatic diseases.

Enhances the effect of benzodiazepine drugs, antidepressants, anxiolytics, antiepileptic drugs (carbamazepine) and antiparkinsonian drugs (levodopa), nitrates.

Reduces the toxic effect of ethanol.

Storage Conditions

The drug should be stored in the secondary packaging in a place inaccessible to children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years. Do not use after the expiration date.

Dispensing Status

The drug is available without a 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.