Mexitex

INSTRUCTION for medical use of the medicinal product MEXITEK (MEXITEK)

Composition:

Active substance: ethylmethylhydroxypyridine succinate;

1 ml of solution contains ethylmethylhydroxypyridine succinate 50 mg;

Excipients: sodium metabisulfite (E 223), water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: colorless or slightly yellowish clear liquid.

Pharmacotherapeutic group. Agents affecting the nervous system. ATC code N07X X.

Pharmacological Properties

Pharmacodynamics

Mexitil is an inhibitor of free radical processes and a membrane protector, exerting anti-hypoxic, stress-protective, nootropic, anticonvulsant, and anxiolytic effects. The drug enhances the body's resistance to various harmful factors and to oxygen-dependent pathological conditions (shock, hypoxia and ischemia, impaired cerebral circulation, alcohol intoxication, and intoxication with antipsychotic agents (neuroleptics)).

Mexitil improves cerebral metabolism and cerebral blood supply, enhances microcirculation and blood rheological properties, and reduces platelet aggregation. It stabilizes blood cell membrane structures (erythrocytes and platelets) during hemolysis. It exerts a hypolipidemic effect by reducing total cholesterol and low-density lipoprotein (LDL) levels. It reduces enzymatic toxemia and endogenous intoxication in acute pancreatitis.

The mechanism of action of the drug is due to its antioxidant and membrane-protective effects. It inhibits lipid peroxidation, increases superoxide dismutase activity, improves the lipid-to-protein ratio, reduces membrane viscosity, and enhances membrane fluidity. It modulates the activity of membrane-bound enzymes (calcium-independent phosphodiesterase, adenylate cyclase, acetylcholinesterase) and receptor complexes (benzodiazepine, γ-aminobutyric acid (GABA), acetylcholine), thereby enhancing their ability to bind ligands, promoting preservation of the structural and functional organization of biomembranes, neurotransmitter transport, and improving synaptic transmission. Ethylmethylhydroxypyridine succinate increases dopamine levels in the brain. It enhances compensatory activation of aerobic glycolysis and reduces the degree of inhibition of oxidative processes in the Krebs cycle under hypoxic conditions, leading to increased levels of adenosine triphosphate (ATP) and creatine phosphate, activation of mitochondrial energy-producing functions, and stabilization of cellular membranes.

Ethylmethylhydroxypyridine succinate normalizes metabolic processes in ischemic myocardium, reduces the area of necrosis, restores and improves myocardial electrical activity and contractility, increases coronary blood flow in the ischemic area, reduces consequences of reperfusion syndrome in acute coronary insufficiency, and enhances the antianginal activity of nitrate drugs. Ethylmethylhydroxypyridine succinate helps preserve retinal ganglion cells and optic nerve fibers in progressive neuropathy caused by chronic ischemia and hypoxia. It improves functional activity of the retina and optic nerve and increases visual acuity.

Pharmacokinetics

After intramuscular administration, the drug is detectable in blood plasma for up to 4 hours after injection. Time to reach maximum concentration is 0.45–0.5 hours. Maximum concentration at doses of 400–500 mg ranges from 3.5 to 4.0 μg/mL. Ethylmethylhydroxypyridine succinate rapidly transfers from the bloodstream into organs and tissues and is quickly eliminated from the body. The drug is excreted primarily in urine, mainly as glucuronide conjugates, and to a minor extent unchanged.

Clinical characteristics.

Indications.

Acute cerebrovascular disorders;

traumatic brain injury, consequences of traumatic brain injuries;

dyscirculatory encephalopathy;

chronic cerebral ischemia;

vegetative dystonia syndrome;

mild (moderate) cognitive disorders;

anxiety disorders in neurotic and neurosis-like conditions;

acute myocardial infarction (from the first day), as part of combination therapy;

primary open-angle glaucoma at various stages, as part of combination therapy;

management of alcohol withdrawal syndrome with predominance of neurosis-like and neurocirculatory disturbances;

acute intoxication with antipsychotic agents;

acute purulent-inflammatory processes in the abdominal cavity (acute necrotic pancreatitis, peritonitis), as part of combination therapy.

Contraindications.

Acute liver or renal failure, increased individual sensitivity to the active substance and/or to excipients of the medicinal product.

Pregnancy or breastfeeding period. Pediatric age.

Interaction with other medicinal products and other types of interactions.

When used concomitantly, the medicinal product Mexitec enhances the effect of benzodiazepine anxiolytics, anticonvulsants (carbamazepine), and antiparkinsonian agents (levodopa). Reduces the toxic effect of ethanol. Enhances the antianginal activity of nitro compounds and the antihypertensive activity of angiotensin-converting enzyme (ACE) inhibitors and β-adrenoblockers. Concurrent use with nibentan, propranolol, and verapamil reduces the risk of developing arrhythmogenic effects of these agents; concurrent use with neuroleptics reduces the risk and severity of their adverse reactions.

Special precautions for use

In individual cases, especially in susceptible patients and in patients with bronchial asthma with increased sensitivity to sulfites, severe hypersensitivity reactions may occur. The medicinal product contains sodium metabisulfite, which may cause bronchospasm.

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e. it is practically sodium-free.

The medicinal product Mexitek should be used with caution in patients with diabetic retinopathy (the course should not exceed 7–10 days) due to its ability to potentiate proliferative processes.

After completion of parenteral administration, to maintain the achieved effect, continuation of the treatment with the drug in tablet form orally is recommended.

Use during pregnancy or breastfeeding.

Pregnancy. There are no data on the use of ethylmethylhydroxypyridine succinate in pregnant women. Reproductive toxicity studies in animals do not indicate the presence of direct or adverse effects. The medicinal product is contraindicated during pregnancy.

Lactation period. There is no information on the penetration of ethylmethylhydroxypyridine succinate (metabolites) into human breast milk. The medicinal product is contraindicated during breastfeeding.

Fertility. Reproductive toxicity studies in animals do not indicate the presence of reproductive toxicity.

Ability to affect reaction speed when driving or operating machinery.

During treatment with the drug, caution should be exercised in activities requiring rapid psychomotor reactions (e.g. driving vehicles, operating machinery).

Method of Administration and Dosage.

The regimen depends on the disease.

Intramuscularly or intravenously (bolus or infusion). When administered by infusion, the drug should be diluted in 100–150 mL of 0.9% sodium chloride solution or 5% glucose solution. Mexitek should be administered intravenously as a slow bolus over 5–7 minutes; for infusion, the rate should be 40–60 drops per minute. The maximum daily dose should not exceed 1200 mg.

In acute cerebral circulation disorders: During the first 10–14 days, administer Mexitek intravenously by infusion at 200–500 mg 2–4 times daily. Then switch to intramuscular administration of 200–250 mg 2–3 times daily for 14 days, followed by transition to oral dosage forms.

In traumatic brain injury and its sequelae: Administer Mexitek by intravenous infusion at 200–500 mg 2–4 times daily for 10–15 days, followed by transition to oral dosage forms.

In decompensated phase of dyscirculatory encephalopathy: Administer Mexitek intravenously either as bolus or infusion at 200–500 mg 1–2 times daily for 14 days. Then administer intramuscularly at 100–250 mg daily for the next 2 weeks, followed by transition to oral dosage forms.

For course prophylaxis of dyscirculatory encephalopathy: Administer the drug intramuscularly at 200–250 mg twice daily for 10–14 days, followed by transition to oral dosage forms.

In chronic cerebral ischemia: Administer the drug at 10 mL (500 mg) once daily by intravenous infusion or slow intravenous bolus for 14 days, followed by transition to oral dosage forms.

In mild (moderate) cognitive impairments in elderly patients: Administer the drug at 10 mL (500 mg) once daily by intravenous infusion or slow intravenous bolus for 14 days, followed by transition to oral dosage forms.

In anxiety disorders: Administer the drug intramuscularly at a daily dose of 100–300 mg for 14–30 days, followed by transition to oral dosage forms.

In acute myocardial infarction: Administer Mexitek intravenously or intramuscularly for 14 days as part of conventional myocardial infarction therapy, including nitrates, β-adrenoblockers, ACE inhibitors, thrombolytics, anticoagulant and antiplatelet agents, as well as symptomatic treatment as indicated. Intravenous administration is preferred during the first 5 days to achieve maximum effect; intramuscular administration may be used during the subsequent 9 days. Intravenous infusion should be performed slowly (to avoid adverse reactions) in 100–150 mL of 0.9% sodium chloride solution or 5% glucose solution over 30–90 minutes. If necessary, slow bolus injection may be administered over no less than 5 minutes.

Administration of Mexitek (intravenous or intramuscular) should be performed 3 times daily, every 8 hours. The daily therapeutic dose is 6–9 mg per kg of body weight; the single dose is 2–3 mg/kg. The maximum daily dose should not exceed 800 mg, and the maximum single dose should not exceed 250 mg.

In open-angle glaucoma of various stages: Administer the drug as part of combination therapy intramuscularly at 100–300 mg daily, 1–3 times daily for 14 days.

In alcohol withdrawal syndrome: Administer at a dose of 200–500 mg intravenously or intramuscularly 2–3 times daily for 5–7 days.

In acute intoxication with antipsychotic agents: Administer the drug intravenously at 200–500 mg daily for 7–14 days.

In acute purulent-inflammatory processes in the abdominal cavity (acute necrotizing pancreatitis, peritonitis): Administer the drug on the first day both pre- and post-operatively. Doses depend on the form and severity of the disease, extent of the process, and clinical presentation. Discontinuation of the drug should be gradual and only after a stable positive clinical and laboratory response.

In acute edematous (interstitial) pancreatitis: Administer the drug at 200–500 mg 3 times daily by intravenous infusion (in isotonic sodium chloride solution) and intramuscularly. Mild severity of necrotizing pancreatitis: 100–200 mg 3 times daily by intravenous infusion (in isotonic sodium chloride solution) and intramuscularly. Moderate severity: 200 mg 3 times daily by intravenous infusion (in isotonic sodium chloride solution). Severe course: Pulse-dose regimen of 800 mg on the first day with twice-daily administration; then 200–500 mg twice daily with gradual reduction of the daily dose. Very severe course: Initial dose of 800 mg daily until stable resolution of pancreatogenic shock; after stabilization, administer 300–500 mg twice daily by intravenous infusion (in isotonic sodium chloride solution) with gradual reduction of the daily dose.

Elderly patients: Dose adjustment in elderly patients is not required.

Children: Use is contraindicated.

Overdose.

Symptoms: Drowsiness, insomnia.

Treatment: Due to the low toxicity, overdose is unlikely. Treatment is usually not required; symptoms resolve spontaneously within 24 hours. In cases of pronounced symptoms, supportive and symptomatic treatment should be administered.

Side effects

To avoid adverse reactions, it is recommended to adhere to the recommended dosage regimen and rate of administration. The frequency of adverse reactions was determined according to the classification of the World Health Organization (WHO): very common (≥10%); common (≥1% to ≤10%); uncommon (≥0.1% to ≤1%); rare (≥0.01% to ≤0.1%); very rare (≤0.01%); frequency not known (frequency cannot be determined from available data).

Immune system disorders: very rare – anaphylactic shock, angioneurotic edema, urticaria; frequency not known – allergic reactions, hyperemia, possible severe hypersensitivity reactions.

Psychiatric disorders: very rare – drowsiness; frequency not known – sleep disturbances, anxiety, emotional reactivity.

Cardiac disorders: frequency not known – palpitations, tachycardia.

Nervous system disorders: very rare – headache, dizziness (may be related to excessively rapid administration and is usually transient); frequency not known – coordination disorders, tremor.

Vascular disorders: very rare – decreased/increased arterial pressure (may be related to excessively rapid administration and is usually transient).

Respiratory, thoracic and mediastinal disorders: very rare – dry cough, throat irritation, chest discomfort, dyspnea (may be related to excessively rapid administration and is usually transient); frequency not known – bronchospasm.

Gastrointestinal disorders: very rare – dry mouth, nausea, unpleasant odor sensation, metallic taste in the mouth; frequency not known – dyspeptic disorders, diarrhea.

Skin and subcutaneous tissue disorders: very rare – itching, rash, facial hyperemia; frequency not known – distal hyperhidrosis.

General disorders and administration site conditions: very rare – sensation of warmth; frequency not known – changes at the injection site.

With prolonged administration of the drug, the following adverse reactions may occur: flatulence, weakness, peripheral edema.

Reporting of adverse reactions

Reporting suspected adverse reactions after drug registration is important. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Incompatibilities.

The drug should not be mixed with other medicinal products. Use only the solvents specified in the instructions.

Packaging.

2 ml in an ampoule; 5 ampoules in a blister, 2 blisters in a carton, or 5 ml in an ampoule; 5 ampoules in a blister, 1 blister in a carton.

Prescription status. Prescription only.

Manufacturer. Private Joint-Stock Company "Lekhym-Kharkiv".

Manufacturer's address and location of operations.

36 Severina Pototskoho Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.