Alakor

INSTRUCTIONS for medical use of the medicinal product ALACOR (ALACOR)

Composition:

Active substance: emoxypirium succinate;

1 ml of solution contains emoxypirium succinate, calculated as 100 % substance – 50 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.

Alcor 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, cerebral circulation disorders, alcohol intoxication, and intoxication with antipsychotic agents (neuroleptics)).

The drug improves cerebral metabolism and cerebral blood supply, enhances microcirculation and rheological properties of blood, and reduces platelet aggregation. It stabilizes membrane structures of blood cells (erythrocytes and platelets) during hemolysis. Alcor 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–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 improvement of synaptic transmission. Ethylmethylhydroxypyridine succinate increases dopamine levels in the brain. It enhances 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.

Ethylmethylhydroxypyridine succinate normalizes metabolic processes in ischemic myocardium, reduces the necrotic area, restores and improves electrical activity and contractility of the myocardium, increases coronary blood flow in the ischemic zone, and reduces consequences of reperfusion syndrome in acute coronary insufficiency. It enhances the antianginal activity of nitrate drugs. Ethylmethylhydroxypyridine succinate promotes preservation of 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 post-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. Ethylmethylhydroxypyridine succinate rapidly transfers from the bloodstream into organs and tissues and is rapidly eliminated from the body. The drug is excreted primarily in urine, mainly as glucuronide conjugates, and in small amounts 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 complex therapy;

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

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

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 Alacor enhances the effect of benzodiazepine anxiolytics, anticonvulsants (carbamazepine), and antiparkinsonian agents (levodopa). It reduces the toxic effect of ethanol. It increases the antianginal activity of nitrocompounds 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.

Use 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 effect, it is recommended to continue treatment orally with tablets.

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

Use during pregnancy or breastfeeding.

Pregnancy. There are no data on the use of ethylmethylhydroxypyridine succinate in pregnant women. Animal reproductive toxicity studies 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 ethylmethylhydroxypyridine 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 influence reaction speed when driving or operating machinery.

During treatment with this drug, caution is advised for activities requiring rapid psychomotor reactions (e.g., driving vehicles or operating machinery).

Method of Administration and Dosage.

The administration regimen depends on the disease.

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

In acute cerebral circulation disorders, Alakor should be administered intravenously by infusion during the first 10–14 days at a dose of 200–500 mg 2–4 times daily, followed by intramuscular administration of 200–250 mg 2–3 times daily for 14 days, after which transition to oral dosage forms is recommended.

In traumatic brain injury and its sequelae, Alakor should be administered intravenously by infusion for 10–15 days at a dose of 200–500 mg 2–4 times daily, after which transition to oral dosage forms is recommended.

In decompensated phase of dyscirculatory encephalopathy, Alakor should be administered intravenously by bolus or infusion at a dose of 200–500 mg 1–2 times daily for 14 days. Then the drug should be administered intramuscularly at 100–250 mg daily for the following 2 weeks, after which transition to oral dosage forms is recommended.

For course prophylaxis of dyscirculatory encephalopathy, the drug should be administered intramuscularly at 200–250 mg twice daily for 10–14 days, after which transition to oral dosage forms is recommended.

In chronic cerebral ischemia, the drug should be administered at 10 mL (500 mg) once daily by intravenous infusion or by slow intravenous bolus injection for 14 days, after which transition to oral dosage forms is recommended.

In mild (moderate) cognitive disorders in elderly patients, the drug should be administered at 10 mL (500 mg) once daily by intravenous infusion or by slow intravenous bolus injection for 14 days, after which transition to oral dosage forms is recommended.

In anxiety disorders, the drug should be administered intramuscularly at a daily dose of 100–300 mg for 14–30 days, after which transition to oral dosage forms is recommended.

In acute myocardial infarction, Alakor should be administered 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 of Alakor is preferred during the first 5 days to achieve maximum effect; intramuscular administration may be used during the subsequent 9 days. Intravenous administration of Alakor should be performed by 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 Alakor may be performed over at least 5 minutes.

Administration of Alakor (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, and the single dose must not exceed 250 mg.

In various stages of open-angle glaucoma, the drug should be used as part of combination therapy, administered 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, the drug should be administered intravenously at a dose of 200–500 mg daily for 7–14 days.

In acute purulent-inflammatory processes of the abdominal cavity (acute necrotic pancreatitis, peritonitis), the drug should be administered on the first day both preoperatively and postoperatively. Doses depend on the form and severity of the disease, extent of the process, and clinical course. Discontinuation of the drug should be gradual and only after a stable positive clinical and laboratory response.

In acute edematous (interstitial) pancreatitis, the drug should be administered 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: 800 mg on the first day with twice-daily administration; thereafter, 200–500 mg twice daily with gradual reduction of the daily dose. Very severe course – initial dose of 800 mg daily until persistent control of pancreatogenic shock is achieved; after stabilization of the patient's condition, 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 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.

Adverse reactions

To avoid adverse reactions, it is recommended to adhere to the recommended dosage regimen and rate of administration. The frequency of adverse effects was determined according to the classification of the World Health Organization (WHO): very common (≥10%); common (≥1%, <10%); uncommon (≥0.1%, <1%); rare (≥0.01%, <0.1%); very rare (≤0.01%); frequency not known (frequency cannot be estimated from 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 high infusion rate and is usually transient); frequency not known – coordination disturbances, tremor.

Vascular disorders: very rare – decreased/increased blood pressure (may be related to excessively high infusion rate and is usually transient).

Respiratory, thoracic and mediastinal disorders: very rare – dry cough, throat irritation, chest discomfort, dyspnea (may be related to excessively high infusion rate and is usually transient); 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 marketing authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients or their legal representatives are encouraged to report any 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 and sight of children.

Incompatibilities. The drug must not be mixed with other medicinal products. Only use solvents specified in the instructions.

Packaging. 2 ml in a vial; 5 vials in a blister pack, 2 blisters in a carton.

Prescription status. Prescription only.

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

Manufacturer's address and place of business

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