Neurotop fl

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT NEUROTROP FL

Composition:

active substance: ethylmethylhydroxypyridine succinate;

1 ml of solution contains ethylmethylhydroxypyridine succinate 50 mg;

excipients: sodium metabisulfite, 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. Other agents acting on the nervous system. ATC code N07XX.

Pharmacological Properties

Pharmacodynamics

The drug exerts anti-hypoxic, antioxidant, membrane-protective, nootropic, anxiolytic, stress-protective, and anticonvulsant effects.

It acts as an inhibitor of free-radical processes, suppresses lipid peroxidation, enhances superoxide dismutase activity, increases the lipid-protein ratio, reduces membrane viscosity, and enhances membrane fluidity. By modulating the activity of membrane-bound enzymes (calcium-independent phosphodiesterase, adenylate cyclase, acetylcholinesterase) and receptor complexes (benzodiazepine, gamma-aminobutyric acid (GABA), acetylcholine), and by enhancing their ligand-binding capacity, the drug helps preserve the structural and functional organization of biomembranes, improving neurotransmitter transport and synaptic transmission. It increases dopamine levels in the brain. The medicinal product Neurotop FL enhances compensatory activity of aerobic glycolysis, reduces the degree of suppression of oxidative processes in the Krebs cycle under hypoxic conditions, increases adenosine triphosphate (ATP) and creatine phosphate levels, and activates mitochondrial energy-synthesizing function.

The drug enhances the body's resistance to various stress factors in pathological conditions (shock, hypoxia and ischemia, cerebral circulation disorders, alcohol intoxication, and intoxication with antipsychotic drugs – neuroleptics). Neurotop FL improves brain metabolism and blood supply, microcirculation, and blood rheological properties, and reduces platelet aggregation. It stabilizes blood cell membranes (erythrocytes and platelets), preventing hemolysis. The drug exerts a hypolipidemic effect, reducing total cholesterol and low-density lipoprotein (LDL) levels. It reduces enzymatic toxemia and endogenous intoxication in acute pancreatitis. The drug 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 the consequences of reperfusion syndrome in acute coronary insufficiency, and enhances the antianginal activity of nitro-compounds.

Neurotop FL 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, increasing visual acuity.

Pharmacokinetics

Absorption. After administration of Neurotop FL at doses of 400–500 mg, maximum plasma concentration (Cmax) reaches 3.5–4.0 mcg/mL within 0.45–0.5 hours.

Distribution. Rapidly distributes from the bloodstream into organs and tissues. After intramuscular administration, the drug is detectable in plasma for up to 4 hours. The mean retention time of the drug in the body is 0.7–1.3 hours.

Metabolism. Metabolized in the body via intensive conjugation with glucuronic acid.

Elimination. Rapidly excreted in urine, primarily in glucuronide-conjugated form, and to a minor extent unchanged.

Clinical characteristics.

Indications.

• Acute cerebrovascular disorders;
• Dyscirculatory encephalopathy;
• Neurocirculatory dystonia;
• Craniocerebral trauma, consequences of craniocerebral injuries;
• Mild cognitive disorders of atherosclerotic origin;
• Acute myocardial infarction (from the first day) – as part of combination therapy;
• Anxiety disorders in neurotic and neurosis-like conditions;
• Alcohol withdrawal syndrome with predominant neurosis-like and vegetative-vascular disorders;
• Acute intoxication with antipsychotic agents;
• Acute purulent-inflammatory processes in the abdominal cavity (acute necrotizing pancreatitis, peritonitis) – as part of combination therapy;
• Primary open-angle glaucoma (at all stages) – as part of combination therapy.

Contraindications.

• Hypersensitivity to the drug;
• Acute hepatic and renal function impairment;
• Childhood;
• Pregnancy;
• Lactation period.

Interaction with other medicinal products and other types of interactions.

The medicinal product Neurotop FL enhances the effects of benzodiazepine anxiolytics, anticonvulsants (carbamazepine), and antiparkinsonian agents (levodopa). It potentiates the effects of nitro-containing drugs and antihypertensive agents. It reduces the toxic effect of ethanol. It increases the antianginal activity of nitro-drugs 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.

In individual cases, especially in patients with a limited allergic history, in patients with bronchial asthma, or with increased sensitivity to sulfites, severe hypersensitivity reactions may occur.

The medicinal product contains sodium metabisulfite, which may cause hypersensitivity reactions and bronchospasm.

The medicinal product should be used 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 achieved effect, continuation of the treatment with the drug orally in tablet form is recommended.

Use during pregnancy or breastfeeding.

Controlled clinical studies on the safety of the drug during pregnancy and breastfeeding have not been conducted. The use of the drug is contraindicated during pregnancy and breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

During treatment with this drug, driving vehicles or operating machinery, including complex technical equipment, machines, or any other complex devices requiring high attention concentration and rapid reaction, is not recommended.

Administration and Dosage

Intramuscularly or intravenously (by bolus or infusion). Doses are individually adjusted. When administered by infusion, the drug should be diluted in physiological saline solution (sodium chloride).

The drug is administered intravenously by bolus injection slowly over 5–7 minutes; by infusion, at a rate of 40–60 drops per minute.

Treatment in adults is initiated at a dose of 50–100 mg 1–3 times daily, gradually increasing the dose until the desired therapeutic effect is achieved. The maximum daily dose should not exceed 800 mg.

In acute cerebral circulation disorders: in combined therapy, administer intravenously (by bolus or infusion) to adults 200–300 mg once daily for the first 2–4 days, followed by intramuscular administration of 100 mg three times daily. Treatment duration is 10–14 days.

In traumatic brain injury and its consequences: administer intravenously by infusion 200–500 mg 2–4 times daily for 10–15 days.

In dyscirculatory encephalopathy (decompensation phase): intravenously by bolus or infusion at a dose of 100 mg 2–3 times daily for 14 days. Then continue with intramuscular administration of 100 mg daily for the following 2 weeks.

For course prophylaxis of dyscirculatory encephalopathy: administer intramuscularly to adults 100 mg twice daily for 10–14 days.

In mild cognitive impairment in elderly patients and anxiety states: administer intramuscularly at a dose of 100–300 mg daily for 14–30 days.

In acute myocardial infarction as part of combination therapy: administer intravenously or intramuscularly for 14 days, alongside conventional myocardial infarction therapy including nitrates, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, thrombolytics, anticoagulants and antiplatelet agents, as well as symptomatic treatments as indicated. For maximum effect during the first 5 days, intravenous administration is preferred. For the subsequent 9 days, transition to intramuscular administration is possible. Intravenous administration should be performed by slow infusion (to avoid adverse effects) in 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 the drug may be administered over no less than 5 minutes.

The drug is administered (intravenously or intramuscularly) three times daily every 8 hours. The daily therapeutic dose is 6–9 mg/kg body weight; the single dose is 2–3 mg/kg body weight. The maximum daily dose should not exceed 800 mg; the maximum single dose should not exceed 250 mg.

In neurocirculatory dystonia: intramuscularly 100–200 mg once or twice daily for 10–15 days.

In open-angle glaucoma at various stages as part of combination therapy: administer intramuscularly 100–300 mg daily in 1–3 divided doses for 14 days.

In alcohol withdrawal syndrome: administer at a dose of 100–200 mg intramuscularly 2–3 times daily or intravenously by infusion 1–2 times daily for 5–7 days.

In acute intoxication with antipsychotic agents: administer intravenously to adults at a dose of 50–300 mg daily for 7–14 days.

In acute purulent-inflammatory processes in the abdominal cavity (acute necrotizing pancreatitis, peritonitis): the drug should be prescribed 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 is achieved.

In acute edematous (interstitial) pancreatitis: administer to adults 100 mg three times daily intravenously by infusion (in isotonic sodium chloride solution) and intramuscularly.

In mild necrotizing pancreatitis: administer 100–200 mg three times daily intravenously by infusion (in isotonic sodium chloride solution) and intramuscularly.

In moderate necrotizing pancreatitis: administer to adults 200 mg three times daily intravenously by infusion (in isotonic sodium chloride solution).

In severe necrotizing pancreatitis: initial dose of 800 mg on the first day administered twice daily, followed by 300 mg twice daily, with gradual reduction of the daily dose.

In very severe course: initial dose is 800 mg daily until persistent control of pancreatogenic shock is achieved; after stabilization of the patient's condition, administer 300–400 mg twice daily intravenously by infusion (in isotonic sodium chloride solution), with gradual dose reduction.

Children.

No well-controlled clinical studies on the safety of the drug in children have been conducted; therefore, the medicinal product Neirotrop FL is contraindicated in this patient group.

Overdose.

In case of overdose, drowsiness or insomnia may occur. With intravenous administration, transient and slight increase in arterial blood pressure may occur in individual cases. Treatment consists of detoxification therapy. Development of overdose symptoms usually does not require specific antidotal treatment. Sleep disturbances resolve spontaneously within 24 hours. In particularly severe cases, administration of one of the oral sedative and anxiolytic agents (nitrazepam 10 mg, oxazepam 10 mg, or diazepam 5 mg) may be recommended. In case of excessive increase in arterial pressure, antihypertensive agents should be used under arterial pressure monitoring and/or therapy should be supplemented with nitrate-containing drugs.

Side effects.

To avoid the occurrence of 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%, 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, feeling of anxiety, emotional reactivity.

Cardiac disorders: frequency not known – palpitations, tachycardia.

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

Vascular disorders: very rare – decreased blood pressure, increased blood pressure (may be related to excessively high rate of infusion and 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 infusion and transient in nature); 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 suspected adverse reactions

Reporting suspected adverse reactions after drug registration is important. It allows 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 cases of suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions. Store at temperatures not exceeding 25 °C in a place protected from light. Keep out of reach of children.

Incompatibilities.

Cases of incompatibility with drugs from other pharmacological groups have not been described.

Packaging.

2 ml in amber glass vials, stoppered with rubber stoppers and sealed with red aluminum caps with flip-off seals. 5 vials in a transparent blisters pack. 1 blister pack in a cardboard box.

4 ml in amber glass vials, stoppered with rubber stoppers and sealed with red aluminum caps. 5 vials in a transparent blisters pack. 1 blister pack in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

JSC "Likvor".

Manufacturer's address and location of manufacturing activities.

7/9 Kochinyan Street, Yerevan 0089, Republic of Armenia.

Marketing authorization holder. JSC "FarmLiga" / UAB "Farmlyga".

Address of the marketing authorization holder. Antakalnio g. 48A-304, Vilnius, Republic of Lithuania / Antakalnio g. 48A-304, Vilnius, Republic of Lithuania.