1. Name of the drug

Mexidol®, 125 mg, tablets covered with film shell

2. Qualitative and quantitative composition

Active substance: ethylmethylhydroxypyridine succinate.
1 tablet contains: ethylmethylhydroxypyridine succinate - 125.0 mg.
Excipients, the presence of which must be taken into account as part of the drug: lactose monohydrate.
A full list of excipients is given in section 6.1.

3. Dosage form

Tablets covered with a film shell.
Round, biconvex pills covered with a film membrane, from white to white with a yellowish tint of color, the presence of a characteristic smell is allowed.

4. Clinical data

Indications for use

• The consequences of acute cerebrovascular accident, including after transient ischemic attacks, in the subcompensation phase as preventive courses;
• light cranial injury, consequences of traumatic brain injuries;
• encephalopathy of various genes (discirculatory, dysmetabolic, post -traumatic, mixed);
• vegetative dystonia syndrome;
• light cognitive disorders of atherosclerotic genesis;
• alarming disorders in neurotic and neurosis -like conditions;
• coronary heart disease in complex therapy;
• the relief of withdrawal syndrome in alcoholism with a predominance of neurosis-like and vegetative-vascular disorders, postbustified disorders;
• condition 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;
• impact of extreme (stressor) factors;
• Syndrome of attention deficiency with hyperactivity (ADHD) in children, including hyperactivity, impaired attention, impulsiveness.

4.3. Dosing mode and method of application

Dosage mode
for 125-250 mg 3 times a day; The maximum daily dose is 750 mg. The duration of treatment is 2-8 weeks; To stop alcohol withdrawal-5-7 days. Treatment is stopped gradually, reducing the dose within 2-3 days.
The initial dose is 125-250 mg (1-2 tablets) 1-2 times a day with a gradual increase until the therapeutic effect is obtained.
To treat the consequences of acute cerebral circulation disorders, including after transient ischemic attacks, tablets are prescribed after the course of the drug in the form of a solution for intravenous and intramuscular administration.
The duration of the course of therapy in patients with coronary heart disease is at least 1.5-2 months. Repeated courses (on the recommendation of a doctor) are advisable to conduct in the spring-autumn periods.

Children
with syndrome of attention deficiency with hyperactivity (ADHD) in children, including hyperactivity, impaired attention, impulsiveness: 125 mg 2 times a day for 6 weeks.

The method of use
inward, washed down with water.

4.3. Contraindications

• increased individual sensitivity to the drug and its components listed in section 6.1;
• acute impaired liver and/or kidneys;
• children's age up to 6 years (due to insufficient knowledge of the drug);
• pregnancy, breastfeeding (due to insufficient knowledge of the drug);
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorbation.

4.4. Special instructions and precautions when applying

Patients with rarely encountered by hereditary intolerance to galactose, deficiency of lactase, glucose-galactose malabsorption should not take this drug.

4.5. Interaction with other drugs and other types of interaction

Mexidol® combines with all drugs used to treat somatic diseases. Enhances the action of benzodiazepine drugs, antidepressants, anxiolytics, anticonvulsants and anti -parquinsonical agents. Reduces toxic effects of ethyl alcohol.

4.6. Fertility, pregnancy and lactation

The drug Mexidol® is contraindicated during pregnancy and during breastfeeding.

4.7. Influence on the ability to drive vehicles and work with mechanisms

During the intake of the drug, caution should be observed when working that requires the speed of psychophysical reactions (driving vehicles, mechanisms, etc.).

4.8. Unwanted reactions

The resume of unwanted reactions
of the frequency of side effects was determined in accordance with the classification of the World Health Organization (WHO): very often (≥ 10 %); often (≥ 1 %, but ˂ 10 %); infrequently (≥ 0.1 %, but ˂ 1 %); rarely (≥ 0.01 %, but ˂ 0.1 %); very rarely (˂ 0.01 %); The frequency is unknown (the frequency cannot be determined on the basis of the available data).
Violations of the immune system: very rarely - angioedema, urticaria.
Mental disorders: very rarely - drowsiness.
Violations of the nervous system: very rarely - headache.
Gastrointestinal disorders: very rarely-dry mouth, nausea, pain, burning and discomfort in the epigastric region, heartburn, flatulence, diarrhea.
Disorders from the skin and subcutaneous tissues: very rarely - rash, itching, hyperemia.

report suspects of unwanted reactions
to report suspects of unwanted reactions after registering the drug in order to ensure continuous monitoring of the “benefit - risk” of the drug. Medical workers are recommended to report any suspects of undesirable reactions of the drug through national systems of reports about undesirable reactions of the member states of the Eurasian Economic Union.

4.9. Overdose

Symptoms
of drowsiness, insomnia.

Treatment
due to low toxicity overdose is unlikely. Treatment, as a rule, is not required - symptoms disappear independently during the day. With severe manifestations, supportive and symptomatic treatment is performed.

5. Pharmacological properties

5.1. Farmacodynamic properties

Pharmacotherapeutic group: antioxidant.
ATX Code: N07XX.

The mechanism of action
Mexidol® action is due to its antioxidant, antihyplance and membraneprotective effects. It inhibits the peroxidation of lipids, increases the activity of superoxidsmutase, increases the ratio of lipid-beam, reduces the viscosity of the membrane, and increases its fluidity. Mexol® modulates the activity of membrane enzymes (calcium-dependent phosphodesturas, adenilatziclase, acetylcholinersterase), receptor complexes (benzodiazepine, gamut, acetylcholine), which enhances their ability to bind ligands, and the preservation of the structural and functional organization of biomembrane, transport of neurudialists and improved synaptic transmission. It causes an increase in the compensatory activation of aerobic glycolysis and a decrease in the degree of inhibition of oxidative processes in the Crebs cycle in conditions of hypoxia with an increase in the content of ATP and creatine phosphate, activation of energy synthetic functions of mitochondria, and stabilization of cell membranes.
Mexidol® increases the content of dopamine in the brain.

The pharmacodynamic effects
of Mexidol® are an inhibitor of free radical processes, a membraneoprotector with antihypoxic, stress prototive, nootropic, anticonvulsant and anxiolytic effects. The drug increases the body's resistance to various damaging factors (shock, hypoxia and ischemia, cerebrovascular disorders, alcohol intoxication and antipsychotic agents (antipsychotics)). The anti-stress is manifested in the normalization of post-stress behavior, somatovegetative disorders, restoration of sleep-bonding cycles, impaired learning and memory processes, a decrease in dystrophic and morphological changes in various brain structures. It has a hypolipidemic effect, reduces the content of total cholesterol and low density lipoproteins. Mexidol® improves the functional state of ischemized myocardium. In conditions of coronary insufficiency, it increases the collateral blood supply to ischemic myocardium, helps to maintain the integrity of cardiomyocytes and maintain their functional activity. Effectively restores myocardial contractility with reversible heart dysfunction. Stabilizes membrane structures of blood cells (red blood cells and platelets) for hemolysis. The drug improves metabolism and blood supply to the brain, improves microcirculation and rheological properties of blood, reduces platelet aggregation.
Mexidol® reliably reduces the severity of manifestations of the attention deficit syndrome with hyperactivity in children 6-12 years old: reduces the severity of symptoms of inattention, hyperactivity/impulsivity, and contributes to clinical improvement. The use of the drug for ADHD helps to increase the concentration of attention and ability to concentrate, increase perseverance, reduce signs of hyperactivity and reduce impulsiveness, which helps to improve the education and social adaptation of children.
Mexidol® has a pronounced antitoxic effect with withdrawal syndrome. It eliminates the neurological and neurotoxic manifestations of acute alcohol intoxication, restores behavioral disorders, autonomic functions, and is also able to relieve cognitive impairment caused by a long -term technique of ethanol and its abolition. Under the influence of Mexidol®, the action of transcoving, neuroleptic, antidepressant, sleeping pills and anticonvulsants is strengthened, which allows them to reduce their doses and reduce side effects.

The clinical efficiency and safety
randomized double-blind, a clanbo-controlled in parallel groups, the study of the efficiency and safety of the drug Mexidol® Phase III (Epica) with prolonged sequential therapy in patients with hemispheric ischemic strokes in acute and early recovery periods was carried out with the participation of 150 patients aged 40 up to 79 years. Patients were randomized in 2 groups: the first group received therapy with Mexidol® at 500 mg per day intravenously for 10 days with the subsequent reception of 1 tablet (125 mg) 3 times a day for 8 weeks. The Mexidol® therapy group shows a significant decrease in symptoms and functional disorders. When using the drug Mexidol®, a reliably more pronounced improvement in vital functions was noted compared to placebo: at the time of the end of the therapy, the average score on the modified Rankin scale (MSHR) was lower in the Mexidol® (P = 0.04) drug; Also in this group there was a more pronounced dynamics of reducing the average score in MSHR (p = 0.023). The proportion of patients who have reached the recovery corresponding to 0-2 points for MSHR (5 visit) was significantly higher in the Mexidol® drug for the use of a placebo-59 (96.7 %) and 53 (84.1 %), respectively (respectively ( p = 0.039). At the time of the end of the therapy, the neurological deficiency was reliably lower in the therapy group Mexidol®: when testing on a stroke scale of the National Institute for Health at 5, the average value was lower in the first group (p = 0.035). The use of Mexidol® contributed to better functional recovery: the proportion of patients with the lack of problems in space was significantly higher in the first group (p = 0.022). According to the results of subanalysis, the effectiveness of the drug Mexidol® for all the scales used was equal in all age groups. There were no reliable differences in the frequency of unwanted reactions in patients of both groups.
Multicenter-centered dual blind, randomized, placebo-controlled in three parallel groups a clinical study on evaluating the effectiveness and safety of the drug Mexidol® tablets covered with a film shell, in the treatment of attention deficiency syndrome (ADHD) in children 6-12 years old at various modes Dosage (mega) was carried out with the participation of 333 patients.
Based on the results of assessing the final points of efficiency at the end of 6 weeks of therapy, statistically significant changes in the amount of the total score for subx “Inattention”, “Hyperactivity/impulsiveness” of the SNAP-IV scale, the average change in the Snap-IV scales, and the average. Changes in the points on the subshkal “Hyperactivity/impulsivity” of the SNAP-IV scale, the average change in the cones index of the Connses of the SNAP-IV scale, the value of the value on the ADHD Rating Scale IV scale, estimates on the scale of the general clinical impression of the severity of ADHG (Clinical Global Impressions -Adhd-serity, CGI-DHD-S), ratings on the general clinical impression scale-improvement (The Clinical Global Impressions Scale-Improvempent, CGI-I). The superior effectiveness of the drug Mexidol® over a placebo is proven.
Based on the results of the study, statistically significant changes in the sum of the total score for subx “Inattention”, “Hyperactivity/impulsiveness” of the SNAP-IV scale after 6 weeks of therapy were detected in all three research groups (p <0.05). At the same time, between the Mexidol®+placebo and placebo groups, as well as between the Mexidol® and the placebo groups, expressed statistically significant differences were observed (for the PP: P = 0.000308 and P = 0.000024 population, respectively; for the fas: p = 0 population , 000198 and p = 0.000024, respectively). The upper boundary of the 95 %trust interval for the difference in the average main performance indicator in Mexidol®+placebo groups and placebo was -1.22 in PP and -1.33 in the FAS population; In the Mexidol® and placebo groups -3.25 in PP and -3.36 population in the FAS population.
For the FAS population, all patients included in the study, the upper boundary of the 95 %trust interval is a negative value, which allows to state the superior effectiveness of the drug Mexidol® above the placebo. Analysis for the PP population confirms the specified conclusion.
According to the severity of the ADHD on a general clinical impression scale (Clinical Global Impressions-DHD-SEVERITY, CGI-DHD-S), 3 or less points for the end of the therapy were 66 patients in the Mexidol® group (59.46 %), 34 patients in Mexidol®+placebo group (30.63 %) and 25 patients in the placebo group (22.52 %). When evaluating a general clinical impression scale-improvement (The Clinical Global Impressions Scale-IMPROVEMENT, CGI-I) Improvement occurred in 95 (85.59 %) people in the Mexidol® group, 84 (75.68 %) people in the Mexidol® group +Placebo, and in 50 (45.05 %) people in the placebo group, while a significant improvement was observed in 45 (40.54 %) people in the Mexidol®, 20 (18.02 %) person in the Mexidol®+Plaster group+placebo , and in 10 (9.01 %) people - in the placebo group. Between the groups, statistically significant differences were identified (the criterion of χ2 Pieron, p <0.000001).
The results of a statistical analysis of the frequency of the occurrence of NYA, indicators of laboratory tests, and a physically examination demonstrate the absence of significant differences between compared groups in the main safety indicators. The foregoing indicates the comparable nature of the security profiles of the studied dosing of the drug Mexidol® and placebo.

5.2. Pharmacokinetic properties

Absorption
is rapidly absorbed when oral administration. The maximum concentration at doses of 400-500 mg is 3.5-4.0 mcg/ml. It is quickly distributed in organs and tissues.

Distribution of
the average deduction time of the drug in the body when oral administration is 4.9-5.2 hours.

Biotransformation
is metabolized in the liver by glucuronconjuging. 5 metabolites have been identified: 3-oxypyridine phosphate-is formed in the liver and with the participation of alkaline phosphatase disintegrates into phosphoric acid and 3-oxypyridin; The 2nd metabolite is pharmacologically active, formed in large quantities and is found in the urine for 1-2 days after administration; 3rd-is displayed in large quantities in urine; 4th and 5th-Glukuronkonjugat.

Elimation
period of half-life (T1/2) when oral administration is 2.0-2.6 hours. It is quickly excreted in the urine mainly in the form of metabolites and in a small amount-in a constant form. The most intensively displayed during the first 4 hours after taking the drug. Indicators of excretion in the urine of an unchanged drug and metabolites have individual variability.

5.3. Doclinical security data

In the preclinical data obtained according to the results of standard studies of pharmacological safety, toxicity with multiple introduction, genotoxicity, carcinogenic potential, reproductive and ontogenetic toxicity, there was no particular harm to a person.

6. Pharmaceutical properties

6.1. List of excipients

Excipients:
lactose monohydrate;
Povidon K-30;
Magnesium stearat;
Film shell:
gipromellose;
Titanium dioxide;
Lactose monohydrate;
Macrogol;
Tiacetin.

6.2. Incompatibility

Not applicable.

6.3. Shelf life (shelf life)

3 years.
Do not use after the expiration of the expiration date indicated on the packaging.

6.4. Special precautions in storage

Store in a place protected from light at a temperature not exceeding 25 ° C.
Store inaccessible places for children.

6.5. The nature and content of the primary packaging

10 tablets covered with a film shell in a contour cell package from a polyvinyl chloride film and aluminum foil.
1, 2, 3, 4, 5 contour cell packages along with instructions for use in a pack of cardboard.

6.6. Special precautions in the destruction of the used drug or waste obtained after the drug or working with it

There are no special requirements for disposal.

7.

Russia
LLC NPK Pharmasoft
115407, Moscow, ul. Shipbuilding, d. 41, floor 1, pom. 12
tel./ Fax: +7 (495) 626-47-55
Email: Pharmasoft@pharmasoft.ru

7.1. Representative of the holder of the registration certificate

Consumer claims to be sent to the address:
in the Russian Federation:
NPK Farmasoft LLC
115407, Moscow, st. Shipbuilding, d. 41, floor 1, pom. 12
tel./ Fax: +7 (495) 626-47-55
Email: Pharmasoft@pharmasoft.ru

8. Number of registration certificate

LP-No. (000086)-(RG-RU)

9. Date of the first registration (confirmation of registration, re -registration)

Date of the first registration: 10/30/2020

10. Date of text review

The overall characteristics of the drug Mexidol® are available on the information portal of the Eurasian Economic Union in the Internet information and communication network http://www.eurasancommission.org/.