THIAMEX

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT TIAMEX (TIAMEX)

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 acting on the nervous system.

ATC code N07X X.

Pharmacological properties.

Pharmacodynamics.

Thiamex is an inhibitor of free radical processes and a membrane protector that exerts 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, cerebrovascular disorders, alcohol intoxication, and intoxication with antipsychotic agents (neuroleptics)].

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

The mechanism of action of the drug is due to its antioxidant and membrane-protective properties. It inhibits lipid peroxidation, increases superoxide dismutase activity, improves the "lipid–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, gamma-aminobutyric acid [GABA], acetylcholine), thereby enhancing their ligand-binding capacity, supporting the structural and functional organization of biomembranes, facilitating neurotransmitter transport, and improving synaptic transmission. Thiamex increases dopamine levels in the brain. It promotes compensatory activation of aerobic glycolysis and reduces the degree of suppression 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-synthesizing functions, and stabilization of cellular membranes.

Thiamex normalizes metabolic processes in ischemic myocardium, reduces the area of necrosis, restores and improves electrical activity and myocardial contractility, increases coronary blood flow in the ischemic area, and reduces the consequences of reperfusion syndrome in acute coronary insufficiency. It enhances the antianginal activity of nitrocompounds. Thiamex 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 plasma for up to 4 hours post-injection. 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. Thiamex rapidly transfers from the bloodstream into organs and tissues and is rapidly eliminated from the body. The drug is excreted in urine, primarily in glucuronide-conjugated form, with minor amounts excreted unchanged.

Clinical characteristics.

Indications.

• Acute cerebrovascular disorders;
• Traumatic brain injury, consequences of traumatic brain injuries;
• Dyscirculatory encephalopathy;
• Neurocirculatory dystonia;
• Mild cognitive impairments of atherosclerotic origin;
• Anxiety disorders in neurotic and neurosis-like conditions;
• Acute myocardial infarction (from the first day), as part of complex therapy;
• Primary open-angle glaucoma at various stages, as part of complex 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 complex 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 Thiamex enhances the effects of benzodiazepine anxiolytics, anticonvulsant agents (carbamazepine), antiparkinsonian agents (levodopa). It 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. Combined use with nibentan, propranolol, and verapamil reduces the risk of developing arrhythmogenic effects of these agents. Combined use with neuroleptics reduces the risk and severity of their adverse effects.

Special precautions for use.

In individual cases, especially in predisposed patients or 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.

Use with caution in patients with diabetic retinopathy (the course should not exceed 7–10 days) due to its potential to potentiate proliferative processes.

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

Use during pregnancy or breastfeeding.

Use is contraindicated.

Ability to affect reaction rate while driving or operating machinery.

During treatment, caution is necessary when driving or operating complex machinery, considering the possible occurrence of adverse effects that may influence reaction speed and the ability to concentrate.

Method of Administration and Dosage.

Intramuscularly or intravenously (bolus or infusion). When administered by infusion, the drug should be diluted in an isotonic sodium chloride solution. Thiamex should be administered slowly as a bolus over 5–7 minutes, or by drip infusion at a rate of 40–60 drops per minute. The maximum daily dose should not exceed 1200 mg.

In acute cerebral circulation disorders: Thiamex should be used during the first 10–14 days — intravenously by drip infusion, 200–500 mg 2–4 times daily, followed by intramuscular administration of 200–250 mg 2–3 times daily for the next 14 days.

In traumatic brain injury and its sequelae: Thiamex should be administered for 10–15 days by intravenous drip infusion of 200–500 mg 2–4 times daily.

In decompensated phase of dyscirculatory encephalopathy: Thiamex should be administered intravenously either as a bolus or by drip infusion at a dose of 200–500 mg 1–2 times daily for 14 days, followed by intramuscular administration of 100–250 mg daily for the next 2 weeks.

For course prophylaxis of dyscirculatory encephalopathy: the drug should be administered intramuscularly at 200–250 mg twice daily for 10–14 days.

In mild cognitive disorders in elderly patients and in anxiety disorders: the drug should be administered intramuscularly at a daily dose of 100–300 mg daily for 14–30 days.

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

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

In various stages of open-angle glaucoma: Thiamex should be used as part of combination therapy, administered intramuscularly at a dose of 100–300 mg daily, 1–3 times daily for 14 days.

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

In acute intoxication with antipsychotic agents: the drug should be administered intravenously at a dose of 200–500 mg daily for 7–14 days.

In acute purulent-inflammatory processes in the abdominal cavity (acute necrotic pancreatitis, peritonitis): the drug should be administered on the first day both in the preoperative and postoperative periods. Dosage depends 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: Thiamex should be administered at 200–500 mg 3 times daily by intravenous drip infusion (in isotonic sodium chloride solution) and intramuscularly. Mild severity of necrotizing pancreatitis: 100–200 mg 3 times daily by intravenous drip infusion (in isotonic sodium chloride solution) and intramuscularly. Moderate severity: 200 mg 3 times daily by intravenous drip infusion (with isotonic sodium chloride solution). Severe course: pulse-dose regimen of 800 mg on the first day with administration twice daily; followed by 20–500 mg twice daily with gradual reduction of the daily dose. Very severe course: initial dose of 800 mg daily until stable control of pancreatogenic shock symptoms; after stabilization of the patient's condition — 300–500 mg twice daily by intravenous drip infusion (in isotonic sodium chloride solution) with gradual reduction of the daily dose.

Children.

Use is contraindicated.

Overdose.

Symptoms: drowsiness, insomnia.

Treatment: development of overdose symptoms generally does not require specific antidotal therapy. The indicated sleep disturbances resolve spontaneously within 24 hours. In particularly severe cases, one of the oral sedative and anxiolytic agents may be used (nitrazepam 10 mg, oxazepam 10 mg, or diazepam 5 mg). In case of excessive increase in arterial pressure, antihypertensive agents should be used with monitoring of blood pressure and/or therapy should be supplemented with nitrate-containing drugs.

Adverse Reactions

To avoid adverse effects, it is recommended to adhere to the recommended dosing regimen and rate of administration of the medicinal product. The frequency of adverse effects 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 (cannot be estimated based on available data).

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

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

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

Cardiac disorders: frequency not known — palpitations, tachycardia.

Vascular disorders: very rare — decrease/increase in arterial pressure (may be related to excessively high rate of 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 high rate of administration and is transient in nature); frequency not known — bronchospasm.

Gastrointestinal disorders: very rare — dry mouth, nausea, unpleasant taste sensation, metallic taste in 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 effects may occur: flatulence, weakness, peripheral edema.

Reporting of adverse reactions.

Reporting of adverse reactions following marketing authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy of the medicinal product through 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 medicinal product must not be mixed with other medicinal products. Use only solvents specified in the instructions.

Packaging. In 2 ml ampoules, 5 ampoules per blister, 2 blisters per carton; in 5 ml ampoules, 5 ampoules per blister, 1 blister per carton.

Prescription status.

Prescription only.

Manufacturer.

Private Joint-Stock Company "Lekhym-Kharkiv".

Manufacturer's address and location of operations.

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