Instructions for Mexidol®, film-coated tablets, 50 tablets of 125 mg

1. Name of the drug

Mexidol®, 125 mg, film-coated tablets

2. Qualitative and quantitative composition

Active ingredient: ethylmethylhydroxypyridine succinate.
1 tablet contains: 125.0 mg of ethylmethylhydroxypyridine succinate.
Excipients to be considered in the drug formulation: lactose monohydrate.
A complete list of excipients is given in section 6.1.

3. Dosage form

Film-coated tablets.
Round, biconvex, film-coated, white to off-white tablets. A characteristic odor may be present.

4. Clinical data

4.1.Indications

• Consequences of acute cerebral circulation disorders, including those after transient ischemic attacks, in the subcompensation phase as prophylactic courses;
• Mild traumatic brain injury, consequences of traumatic brain injury;
• Encephalopathies of various origin (dyscirculatory, dysmetabolic, post-traumatic, mixed);
• Vegetative dystonia syndrome;
• Mild cognitive disorders of atherosclerotic origin;
• Anxiety disorders in neurotic and neurosis-like states;
• Ischemic heart disease as part of complex therapy;
• The relief of withdrawal syndrome in alcoholism with predominant neurosis-like and vegetative-vascular disorders, post-withdrawal disorders;
• Status post acute antipsychotic intoxication;
• Asthenic conditions, as well as prevention of somatic diseases induced by extreme factors and stress;
• Exposure to extreme (stressful) factors;
• Attention deficit hyperactivity disorder (ADHD) in children, including hyperactivity, disorder of attention, and impulsiveness.

4.2. Dosage and administration:

Dosage regimen
The drug is taken orally, 125–250 mg 3 times a day; the maximum daily dose is 750 mg. Duration of treatment: 2-8 weeks; for alcohol withdrawal relief: 5-7 days. The treatment is discontinued gradually by reducing the dose over 2-3 days. Initial dose: 125-250 mg (1-2 tablets) 1-2 times a day, with gradual up-titration until the therapeutic effect is achieved. For the treatment of consequences of acute cerebral circulation disorders, including those after transient ischemic attacks, tablets should be prescribed following a course of treatment with the solution for intravenous or intramuscular administration. The duration of the therapy course in patients with ischemic heart disease should be at least 1.5-2 months. Repeated courses (as recommended by the physician) are preferably administered in spring and autumn.

Children
Attention deficit hyperactivity disorder (ADHD) in children, including hyperactivity, disorder of attention, and impulsiveness: 125 mg 2 times a day for 6 weeks.

Mode of administration
The drug is taken orally with water.

4.3. Contraindications

• Individual hypersensitivity to the drug or any of its components listed in section 6.1;
• Acute liver and/or kidney dysfunction;
• Pediatric use in children of up to 6 years of age (due to insufficient data on the drug action);
• Pregnancy, breastfeeding (due to insufficient data on the drug action);
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

4.4. Special instructions and precautions for use:

Patients with rare hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this drug.

4.5. Interaction with other drugs and other types of interaction:

Mexidol® is compatible with all drugs used to treat somatic diseases. It enhances the effects of benzodiazepines, antidepressants, anxiolytics, anticonvulsants, and anti-Parkinsonian drugs. The drug reduces the toxic effects of ethyl alcohol.

4.6. Fertility, pregnancy and lactation:

Mexidol® is contraindicated during pregnancy and breastfeeding.

4.7. Effects on ability to drive and use machines

During the drug administration period, caution should be exercised when performing work requiring quick psychophysical reactions (driving vehicles, using machines, etc.).

4.8. Adverse reactions

Summary of adverse reactions
The frequency of side effects was determined pursuant to the World Health Organization (WHO) classification: very common (≥10%), common (≥1 and <10%), uncommon (≥0.1 and <1%), rare (≥0.01% and <0.1%), very rare (<0.01%) and unknown (frequency cannot be determined based on available data). Immune system disorders: very rare – angioedema, urticaria. Mental disorders: very rare – drowsiness. Nervous system disorders: very rare – headache. Gastrointestinal disorders: very rare – dry mouth, nausea, pain, burning and discomfort in the epigastric region, heartburn, flatulence, and diarrhea. Skin and subcutaneous tissue disorders: very rare – rash, itching, hyperemia.

Reporting suspected adverse reactions
It is important to report suspected adverse reactions after the marketing authorization of a drug in order to ensure continuous monitoring of its benefit-risk ratio. Healthcare professionals are advised to report any suspected adverse reactions of the drug through the national adverse reaction reporting systems of the Eurasian Economic Union member states.

4.9. Overdosage

Symptoms
Drowsiness, insomnia

Treatment
Due to low toxicity, overdose is unlikely. Treatment is usually not required, symptoms disappear within a day. In the case of pronounced manifestations, supportive and symptomatic treatment should be administered.

5. Pharmacological properties

5.1. Pharmacology

Pharmacotherapeutic group: antioxidant agent.
ATX Code: N07XX.

Pharmacological action
The pharmacological action of Mexidol® is due to its antioxidant, antihypoxant, and membrane-protective action. It inhibits lipid peroxidation, increases superoxide dismutase activity, increases the lipid-protein ratio, reduces membrane viscosity and increases membrane fluidity. Mexidol® modulates the activity of membrane-bound enzymes (calcium-independent phosphodiesterase, adenylate cyclase, acetylcholinesterase), receptor complexes (benzodiazepine, GABA, acetylcholine), which enhances their ability to bind to ligands, contributes to preserving the structural and functional organization of biomembranes, transporting neurotransmitters and improving synaptic transmission. It causes enhancement of compensatory activation of aerobic glycolysis and reduction of the inhibition rate of oxidative processes in the Krebs cycle under hypoxia with an increased content of ATP, creatine phosphate and activation of energy-synthesizing functions of mitochondria, as well as promotes stabilization of cell membranes. Mexidol® increases dopamine levels in the brain.

Pharmacodynamics
Mexidol® is an inhibitor of free radical processes and a membrane protector with antihypoxic, stress-protective, nootropic, anticonvulsant, and anxiolytic effects. The drug increases the body’s resistance to various damaging factors (shock, hypoxia and ischemia, impaired cerebral circulation, intoxication with alcohol and antipsychotic agents (neuroleptics)). Its anti-stress action is manifested in the normalization of post-stress behavior, somatovegetative disorders, restoration of sleep-wake cycles, improvement of impaired learning and memory processes, and reduction of dystrophic and morphological changes in various brain structures. It has a hypolipidemic effect, reduces the levels of total cholesterol and low-density lipoproteins. Mexidol® improves the functional state of ischemic myocardium. In the case of coronary insufficiency, it increases collateral blood supply to the ischemic myocardium, and helps preserve cardiomyocyte integrity and maintain their functional activity. It effectively restores myocardial contractility in cases of reversible cardiac dysfunction. It stabilizes membrane structures of blood cells (erythrocytes and platelets) in hemolysis. The drug improves metabolism and blood supply to the brain, improves microcirculation and rheological properties of blood, and reduces platelet aggregation.
Mexidol® significantly reduces the severity of attention deficit hyperactivity disorder (ADHD) symptoms in children aged 6 to 12: it decreases inattention, hyperactivity/impulsiveness, and promotes clinical improvement. When used for ADHD, the drug helps increase attentiveness and concentration, improves perseverance, reduces hyperactivity, and decreases impulsiveness, thereby enhancing learning and social adaptation in children. Mexidol® exhibits an pronounced antitoxic action in withdrawal syndrome. It alleviates neurological and neurotoxic manifestations of acute alcohol intoxication, restores behavioral disorders and vegetative functions, and can reverse cognitive deficits caused by prolonged ethanol use and its discontinuation. Mexidol® enhances the effects of tranquilizers, neuroleptics, antidepressants, hypnotics, and anticonvulsants, allowing for dose reduction and minimization of side effects.

Clinical efficacy and safety

5.2. Pharmacokinetics:

Absorption
It is rapidly absorbed when taken orally. The maximum concentration at doses of 400-500 mg is 3.5-4.0 μg/mL. It is quickly distributed to organs and tissues.

Distribution
The mean residence time of the drug in the body after oral administration is 4.9-5.2 hours.

Biotransformation
The drug is metabolized in the liver by glucuronic conjugation. 5 metabolites have been identified: 3-oxypyridine phosphate is formed in the liver and decompounds into phosphoric acid and 3-oxypyridine by alkaline phosphatase; the 2nd metabolite is pharmacologically active, is formed in large quantities and detected in the urine 1-2 days after administration; the 3rd metabolite is excreted in large quantities with urine; the 4th and 5th metaolites are glucuronic conjugates.

Elimation
Half-life (T1/2) after oral administration is 2.0-2.6 hours. It is rapidly excreted in the urine, primarily as metabolites, with only a small amount excreted unchanged. The most intensive excretion occurs within the first 4 hours after the drug administration. The urinary excretion levels of the unchanged drug and its metabolites exhibit individual variability.

5.3. Preclinical safety data

No specific harm to humans has been identified in preclinical data obtained from standardized studies of pharmacological safety, repeated dose toxicity, genotoxicity, carcinogenic potential, reproductive and ontogenetic toxicity.

6. Pharmaceutical properties

6.1. List of excipients

Excipients:
Lactose monohydrate;
Povidon K-30;
Magnesium stearate;
Film coating;
Hypromellose;
Titanium dioxide;
Lactose monohydrate;
Macrogol;
Triacetin.

6.2. Incompatibility:

Not applicable.

6.3. Validity period (shelf life)

3 years.
Do not use the drug after expiration of the shelf life specified on the packaging.

6.4. Special storage precautions:

Store in a place protected from light at a temperature no higher than 25°C.
Keep out of reach of children.

6.5. Description and content of the primary packaging

10 film-coated tablets are packaged in a blister pack made of polyvinyl chloride film and aluminum foil.
1, 2, 3, 4, or 5 blister packs are placed in a carton, along with the package insert.

6.6. Special precautions for disposal of the used drug or waste obtained after the drug administration or handling

There are no special disposal requirements.

7. Marketing authorization holder

PHARMASOFT RESEARCH AND PRODUCTION COMPLEX LLC
Bld. 12, floor 1, 41, Sudostroitelnaya Street, 115407 Moscow, Russia Phone/fax: +7 (495) 626-47-55 E-mail: pharmasoft@pharmasoft.ru

7.1. Representative of the Marketing Authorization Holder

Please address consumer complaints to: In the Russian Federation, PHARMASOFT RESEARCH AND PRODUCTION COMPLEX LLC, Bld. 12, floor 1, 41, Sudostroitelnaya Street, 115407 Moscow, Russia Phone/fax: +7 (495) 626-47-55 E-mail: pharmasoft@pharmasoft.ru

8. Marketing authorization number

ЛП-No.(000086)-(РГ-RU)

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

Date of the first registration: 10/30/2020

10. Text revision date

The summary of product characteristics for Mexidol® is available on the information portal of the Eurasian Economic Union in the Internet information and communication network at http://www.eurasiancommission.org/.