T-mexat

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT T-MEKSAT (T-MEKSAT)

Composition:

Active substance: ethylmethylhydroxypyridine succinate;

1 ampoule (2 ml) of solution contains ethylmethylhydroxypyridine succinate 100 mg;

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

Pharmaceutical form. Solution for injection.

Main physicochemical characteristics: colorless or slightly yellowish clear liquid.

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

Pharmacological Properties

Pharmacodynamics

T-MEXAT is an inhibitor of free radical processes and a membrane protector, exerting antihypoxic, 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, cerebral circulation disorders, alcohol intoxication, and intoxication with antipsychotic agents [neuroleptics]).

T-MEXAT improves cerebral metabolism and cerebral blood supply, enhances microcirculation and rheological properties of blood, and reduces platelet aggregation. It stabilizes blood cell membrane structures (erythrocytes and platelets) during hemolysis. The drug exerts a hypolipidemic effect, reducing levels of total cholesterol and low-density lipoproteins (LDL). 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 increases 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 ligand-binding capacity, supporting the structural and functional organization of biomembranes, neurotransmitter transport, and improving synaptic transmission. Ethylmethylhydroxypyridine succinate increases dopamine levels in the brain. It promotes enhanced compensatory activation of aerobic glycolysis and reduces the degree of inhibition of oxidative processes in the Krebs cycle under hypoxic conditions, resulting in increased levels of adenosine triphosphate (ATP) and creatine phosphate, activation of mitochondrial energy-synthesizing functions, and stabilization of cellular membranes.

Ethylmethylhydroxypyridine succinate normalizes metabolic processes in ischemic myocardium, reduces the necrotic area, restores and improves myocardial electrical activity and contractility, increases coronary blood flow in the ischemic zone, and reduces the consequences of reperfusion syndrome in acute coronary insufficiency. It 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 following administration. Time to reach maximum concentration is 0.45–0.5 hours. Maximum concentration at doses of 400–500 mg is 3.5–4.0 µg/mL. T-MEXAT rapidly transfers from the bloodstream into organs and tissues and is quickly eliminated from the body. The drug is excreted primarily in urine, mainly in glucuronide-conjugated form, with minor amounts excreted unchanged.

Clinical characteristics.

Indications.

Acute cerebrovascular disorders;

head trauma, consequences of head injuries;

dyscirculatory encephalopathy;

chronic cerebral ischemia;

vegetative dystonia syndrome;

mild (moderate) cognitive disorders;

anxiety disorders in neurotic and neuropathic-like conditions;

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

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

management of alcohol withdrawal syndrome with predominance of neurotic-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 hepatic or renal failure, increased individual sensitivity to the active substance and/or to excipients of the medicinal product.

Pregnancy or breastfeeding. Pediatric age.

Interaction with other medicinal products and other types of interactions.

When used concomitantly, the medicinal product enhances the effects of benzodiazepine anxiolytics, anticonvulsants (carbamazepine), and antiparkinsonian agents (levodopa). It reduces the toxic effect of ethanol. It increases the antianginal activity of nitro compounds and the antihypertensive activity of 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 predisposed patients and in patients with bronchial asthma who are hypersensitive 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 T-MEXAT should be used with caution in patients with diabetic retinopathy (the course should not exceed 7–10 days) due to its potential to enhance proliferative processes.

After completion of parenteral administration, to maintain the achieved therapeutic 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 emethylhydroxypyridine succinate in pregnant women. Reproductive toxicity studies in animals do not indicate direct or adverse effects. The medicinal product is contraindicated during pregnancy.

Lactation period. There is no information available on the passage of emethylhydroxypyridine succinate (or its metabolites) into human breast milk. The medicinal product is contraindicated during breastfeeding.

Fertility. Animal reproductive toxicity studies do not indicate reproductive toxicity.

Ability to affect reaction speed when driving or operating machinery

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

Administration and Dosage

The dosing regimen depends on the disease.

Intramuscularly or intravenously (bolus or infusion). For infusion, dilute in 100–150 mL of 0.9% sodium chloride solution or 5% glucose solution. Administer intravenous bolus of T-MEXAT slowly over 5–7 minutes; for intravenous infusion, administer at a rate of 40–60 drops per minute. The maximum daily dose must not exceed 1200 mg.

In acute cerebral circulation disorders: administer T-MEXAT intravenously by infusion at 200–500 mg 2–4 times daily for the first 10–14 days; then switch to intramuscular administration at 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 T-MEXAT 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 T-MEXAT 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 T-MEXAT 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 disorders: administer T-MEXAT 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 T-MEXAT intravenously or intramuscularly for 14 days in addition to conventional myocardial infarction therapy, including nitrates, β-blockers, ACE inhibitors, thrombolytics, anticoagulants, antiplatelet agents, and symptomatic treatments as indicated. Intravenous administration is preferred during the first 5 days to achieve maximum effect; intramuscular administration may be used during the following 9 days. Intravenous administration should be performed as a slow infusion (to avoid adverse reactions) over 30–90 minutes in 100–150 mL of 0.9% sodium chloride solution or 5% glucose solution. If necessary, slow bolus injection may be administered over no less than 5 minutes.

Administration of T-MEXAT (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 must not exceed 800 mg; the maximum single dose must not exceed 250 mg.

In open-angle glaucoma of various stages: administer T-MEXAT as part of combination therapy at 100–300 mg daily (1–3 times daily) intramuscularly for 14 days.

In alcohol withdrawal syndrome: administer T-MEXAT at 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 sustained positive clinical and laboratory response.

In acute edematous (interstitial) pancreatitis: administer T-MEXAT at 200–500 mg 3 times daily by intravenous infusion (in isotonic sodium chloride solution) and intramuscularly.
Light 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, followed by 200–500 mg twice daily with gradual reduction of the daily dose.
Very severe course: initial dose of 800 mg daily until sustained control of pancreatogenic shock is achieved; after stabilization of the patient’s condition, administer 300–500 mg twice daily by intravenous infusion (in isotonic sodium chloride solution) with gradual dose reduction.

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

Children: use is contraindicated.

Overdose

Symptoms: drowsiness, insomnia.

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

Adverse Reactions

To avoid adverse reactions, it is recommended to adhere to the prescribed 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% but ≤10%); uncommon (≥0.1% but ≤1%); rare (≥0.01% but ≤0.1%); very rare (≤0.01%); frequency not known (frequency cannot be estimated based on available data).

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

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

Cardiac disorders: frequency not known – palpitations, tachycardia.

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

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

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

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

Skin and subcutaneous tissue disorders: very rare – pruritus, 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 of adverse reactions after drug registration is highly important. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and pharmacists, 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 the following link: 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. Only use solvents specified in the instructions.

Packaging. 2 mL in an ampoule; 5 ampoules per blister pack, 2 blisters per carton.

Prescription status. Prescription only.

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

Manufacturer's address and location of its business activities.

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