MexiB 6^® (Tablets) Instructions for Use

Marketing Authorization Holder

Canonpharma Production, CJS (Russia)

ATC Code

N07XX (Other drugs for the treatment of nervous system diseases)

Dosage Form

MexiB 6®

Film-coated tablets, 125 mg+10 mg: 10, 15, 20, 30, 60, 90 or 100 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex, with a white or almost white cross-section.

Excipients: calcium hydrogen phosphate dihydrate – 65 mg, calcium stearate – 6.7 mg, copovidone – 14 mg, colloidal silicon dioxide – 20 mg, croscarmellose sodium – 20 mg, magnesium lactate dihydrate – 315.9 mg, magnesium stearate – 6.7 mg, macrogol (polyethylene glycol 6000) – 13.4 mg, microcrystalline cellulose – 53.3 mg.

Film coating composition Opadry white – 20 mg, incl.: hypromellose (hydroxypropyl methylcellulose) – 6.75 mg, hypromellose (hydroxypropyl methylcellulose) – 6.75 mg, talc – 4 mg, titanium dioxide – 2.5 mg.

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (6) – cardboard packs.
10 pcs. – contour cell packaging (10) – cardboard packs.
15 pcs. – contour cell packaging (1) – cardboard packs.
15 pcs. – contour cell packaging (2) – cardboard packs.
15 pcs. – contour cell packaging (4) – cardboard packs.
15 pcs. – contour cell packaging (6) – cardboard packs.

Clinical-Pharmacological Group

Antioxidant drug

Pharmacotherapeutic Group

Other agents for the treatment of nervous system diseases

Pharmacological Action

MexiB 6^® is a combined preparation.

Ethylmethylhydroxypyridine succinate is a free radical process inhibitor – a membrane protector, which also has antihypoxic, stress-protective, nootropic, anticonvulsant, and anxiolytic effects. An antioxidant drug that regulates metabolic processes in the myocardium and vascular wall.

The mechanism of action is due to its antioxidant and membrane-protective properties. It suppresses lipid peroxidation, increases superoxide dismutase activity, affects the physicochemical properties of the membrane, increases the content of polar lipid fractions (phosphatidylserine and phosphatidylinositol, etc.) in the membrane, reduces the cholesterol/phospholipid ratio, reduces the viscosity of the lipid layer and increases membrane fluidity, activates the energy-synthesizing functions of mitochondria and improves energy metabolism in the cell, thus protecting the cellular apparatus and the structure of their membranes.

The drug-induced change in the functional activity of the biological membrane leads to conformational changes in the protein macromolecules of synaptic membranes, as a result of which it has a modulating effect on the activity of membrane-bound enzymes, ion channels, and receptor complexes, in particular, benzodiazepine, GABA, and acetylcholine, enhancing their ability to bind to ligands, increasing the activity of neurotransmitters and the activation of synaptic processes.

It enhances the compensatory activation of aerobic glycolysis and reduces the degree of inhibition of oxidative processes in the Krebs cycle under hypoxia conditions with an increase in adenosine triphosphate (ATP) and creatine phosphate, and activates the energy-synthesizing function of mitochondria.

It increases the body’s resistance to the effects of various damaging factors in pathological conditions (shock, hypoxia and ischemia, cerebrovascular accidents, ethanol intoxication, and antipsychotic drug intoxication).

It improves metabolism and blood supply to the brain, microcirculation and rheological properties of blood, and reduces platelet aggregation.

It stabilizes the membranes of blood cells (erythrocytes and platelets), reducing the likelihood of hemolysis. It has a hypolipidemic effect, reducing the content of total cholesterol and low-density lipoproteins (LDL).

It improves the functional state of the ischemic myocardium, reducing the manifestations of systolic and diastolic dysfunction of the left ventricle (LV), as well as the electrical instability of the myocardium.

Under conditions of a critical decrease in coronary blood flow, it helps to preserve the structural and functional organization of cardiomyocyte membranes, stimulates the activity of membrane enzymes phosphodiesterase, adenylate cyclase, and acetylcholinesterase. It maintains the activation of aerobic glycolysis developing during acute ischemia and promotes the restoration of mitochondrial redox processes under hypoxia conditions, increasing the synthesis of adenosine triphosphate (ATP), creatine phosphate, and other macroergs. It increases collateral blood supply to the ischemic myocardium and activates energy-synthesizing processes in the ischemic zone, which helps to preserve the integrity of cardiomyocytes and maintain their functional activity.

In patients with stable exertional angina, it increases exercise tolerance and the antianginal activity of nitrates, improves the rheological properties of blood, and reduces the incidence of acute coronary insufficiency.

Pyridoxine, entering the body, is phosphorylated, converted into pyridoxal-5-phosphate, and is part of enzymes that carry out the decarboxylation, transamination, and racemization of amino acids, as well as the enzymatic transformation of sulfur-containing and hydroxylated amino acids. It participates in metabolism; it is necessary for the normal functioning of the central and peripheral nervous systems. Pyridoxine is involved in the metabolism of tryptophan, methionine, cysteine, glutamic acid, and other amino acids. It plays an important role in histamine metabolism. It helps to normalize lipid metabolism.

Pharmacokinetics

Ethylmethylhydroxypyridine succinate is rapidly absorbed when taken orally (half-absorption period – 0.08-1 h). Time to reach maximum concentration (T_max) when taken orally is 0.46-0.5 h. Maximum concentration (C_max) when taken orally is 50-100 ng/ml.

It is rapidly distributed in organs and tissues. The mean residence time of ethylmethylhydroxypyridine succinate in the body when taken orally is 4.9-5.2 h.

Ethylmethylhydroxypyridine succinate is metabolized in the liver by glucuronidation. Five metabolites have been identified: 3-oxypyridine phosphate – 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 glucuronide conjugates.

T_1/2 when taken orally is 4.7-5 h. It is rapidly excreted in the urine mainly as metabolites (50% within 12 h) and in small amounts – unchanged (0.3% within 12 h). It is most intensively excreted within the first 4 hours after taking ethylmethylhydroxypyridine succinate. The indicators of excretion of unchanged ethylmethylhydroxypyridine succinate and metabolites in the urine have significant individual variability.

Pyridoxine is rapidly absorbed throughout the entire small intestine.

It is metabolized in the liver to form pharmacologically active metabolites (pyridoxal phosphate and pyridoxamine phosphate).

Pyridoxal phosphate binds to plasma proteins by 90%. It penetrates well into all tissues; it accumulates mainly in the liver, less in muscles and the central nervous system (CNS). It crosses the placenta and is secreted into breast milk.

Half-life (T_1/2) is 15-20 days. It is excreted by the kidneys (with intravenous administration – 2% with bile), and also during hemodialysis.

Indications

As part of combination therapy

• Dyscirculatory encephalopathy;
• Autonomic dystonia syndrome;
• Anxiety disorders in neurotic and neurosis-like states;
• Withdrawal syndrome in alcoholism with a predominance of neurosis-like and autonomic-vascular disorders;
• Coronary heart disease (attack prevention);
• Conditions after acute intoxication with antipsychotic agents;
• Asthenic conditions, as well as for the prevention of the development of somatic diseases under the influence of extreme factors and loads;
• Exposure to extreme (stress) factors.

ICD codes

Dosage Regimen

Administer orally.

Initiate therapy with an initial dose of 1-2 tablets taken 1-2 times daily.

Gradually increase the dose until a therapeutic effect is achieved.

The standard maintenance dosage is 1 tablet taken three times daily.

Do not exceed the maximum daily dose of 6 tablets.

The typical treatment duration is 2 to 8 weeks.

Conduct repeated courses of therapy if necessary, as determined by a physician.

Adverse Reactions

Nausea, dry mouth, diarrhea, drowsiness, allergic reactions, hypersecretion of hydrochloric acid, numbness, sensation of tightness in the extremities – “stocking” and “glove” symptom, decreased lactation (sometimes this is used as a therapeutic effect).

Contraindications

• Hypersensitivity;
• Acute hepatic and/or renal failure;
• Pregnancy;
• Lactation;
• Childhood.

With caution

• Peptic ulcer of the stomach and duodenum.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Contraindicated in acute hepatic failure

Use in Renal Impairment

Contraindicated in acute renal failure

Pediatric Use

Contraindicated in children

Special Precautions

Effect on ability to drive vehicles and operate machinery

During the treatment period, caution must be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Ethylmethylhydroxypyridine succinate

Due to low toxicity, overdose is unlikely. In case of accidental overdose, drowsiness and sedation may occur. Treatment is usually not required – symptoms disappear on their own within 24 hours. In severe cases with insomnia – nitrazepam 10 mg, oxazepam 10 mg or diazepam 5 mg.

Pyridoxine

Taking high doses of pyridoxine over a short period of time (at a dose of more than 1 g per day) may lead to the short-term appearance of neurotoxic effects.

If pyridoxine is taken in a dose exceeding 150 mg/kg of body weight, it is recommended to induce vomiting and take activated charcoal. Inducing vomiting is most effective within the first 30 minutes after taking the drug. Emergency measures may be required.

Drug Interactions

Ethylmethylhydroxypyridine succinate

Enhances the effect of benzodiazepine anxiolytics, anticonvulsants (carbamazepine), antiparkinsonian drugs (levodopa), nitrates. Reduces the toxic effects of ethanol.

Pyridoxine

Enhances the effect of diuretics; weakens the activity of levodopa, combines well with cardiac glycosides (pyridoxine promotes increased synthesis of contractile proteins in the myocardium), with glutamic acid and potassium and magnesium aspartate (increases resistance to hypoxia).

Pyridoxine is pharmaceutically incompatible with thiamine and cyanocobalamin. Isoniazid, penicillamine, cycloserine, and estrogen-containing oral contraceptives weaken the effect of pyridoxine.

Storage Conditions

Store in a place inaccessible to children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years.

Dispensing Status

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.