MetucinVel, 50 mg/ml 2 ml 10 pcs

Pharmacotherapeutic group: antioxidant.

The ATX code: [N07ХХ]

Pharmacological properties

Pharmacodynamics

Ethylmethylhydroxypyridine succinate belongs to 3-oxypyridine class, it is an inhibitor of free radical processes, membrane protector. It also has an antihypoxic effect and increases the body’s resistance to stress.

The mechanism of action of ethylmethylhydroxypyridine succinate is due to its antioxidant and membrane-protective action. The drug inhibits lipid peroxidation, increases the activity of superoxidoxidase, increases the ratio lipid-protein, improves the structure and function of cell membranes.

Ethylmethylhydroxypyridine succinate models the activity of membrane-bound enzymes (calcium-independent phosphodiesterase, adenylate cyclase, acetylcholinesterase), receptor complexes (benzodiazepine, GABA, acetylcholine), which increases their ability to bind to ligands, helps maintain the structural and functional organization of biomembranes, neurotransport and improve synaptic transmission. Ethylmethylhydroxypyridine succinate increases the content of dopamine in the brain. It causes enhancement of compensatory activation of aerobic glycolysis and reduction of the degree of inhibition of oxidative processes in the Krebs cycle under hypoxia with an increase in adenosine triphosphoric acid (ATP) and creatine phosphate, activation of energy-synthesizing functions of mitochondria.

Enhances resistance of the body to various damaging factors in pathological conditions (hypoxia and ischemia, disorders of cerebral circulation, intoxication by ethanol and antipsychotic drugs).

In conditions of critical reduction of coronary blood flow promotes the preservation of structural and functional organization of cardiomyocyte membranes, stimulates the activity of membrane enzymes – phosphodiesterase, adenylate cyclase, acetylcholinesterase. Supports acetylcholinesterase activation that develops in acute ischemia. Supports activation of aerobic glycolysis developing in acute ischemia and promotes under hypoxia restoration of mitochondrial redox processes, increases ATP and creatine phosphate synthesis. Ensures the integrity of morphological structures and physiological functions of ischemic myocardium. Improves clinical course of myocardial infarction, increases the effectiveness of therapy, reduces the incidence of arrhythmias and intracardiac conduction abnormalities.

Normalizes metabolic processes in ischemic myocardium, increases antianginal activity of nitrates, improves rheological properties of blood, reduces consequences of reperfusion syndrome in acute coronary insufficiency.

It promotes the preservation of retinal ganglion cells and optic nerve fibers in progressive neuropathy caused by chronic ischemia and hypoxia. It improves the functional activity of the retina and the optic nerve, increasing visual acuity.

Limits enzymatic toxemia and endogenous intoxication in acute pancreatitis.

It improves metabolism and blood supply of the brain, microcirculation and rheological properties of the blood, reduces platelet aggregation. It stabilizes blood cell membranes (erythrocytes and platelets), reducing the possibility of hemolysis. It has hypolipidemic effect due to the reduction of total cholesterol and low-density lipoproteins.

Pharmacokinetics

In absorption

The maximum concentration (Cmax) in plasma is reached after 0.58 hrs when administered in a dose of 400-500 mg (Cmax) in plasma is 3.5-4 mcg/ml.

Distribution

Rapidly distributed in organs and tissues. Average retention time of ethylmethylhydroxypyridine succinate in the body is 0.7-1.3 h.

Metabolism

Metabolized in the liver by glucuronidation. Five metabolites have been identified: 3-oxypyridine phosphate – formed in the liver and broken down into phosphoric acid and 3-oxypyridine with the help of alkaline phosphatase; the 2nd metabolite – pharmacologically active, formed in large quantities and found in the urine 1-2 days after administration; the 3rd metabolite – excreted in large amounts in the urine; the 4th and 5th – glucuronconjugates. Excretion

Extracted from the blood plasma rapidly and almost undetectable after 4 hours in the blood plasma. It is rapidly excreted in the urine, mainly as metabolites (50% in 12 hours) and in a small amount – in unchanged form (0.3% in 12 hours). Indexes of urinary excretion of unchanged ethylmethylhydroxypyridine succinate and metabolites have individual variability.

Indications

– acute impaired cerebral circulation (as part of complex therapy);

– craniocerebral trauma, consequences of craniocerebral injuries;

– dyscirculatory encephalopathy;

– syndrome of vegetative (neurocirculatory) dystonia;

– mild cognitive disorders of atherosclerotic genesis;

– anxiety disorders with neurotic and neurosis-like conditions;

– acute myocardial infarction (from the first day) as part of complex therapy;

– primary open-angle glaucoma of different stages, as part of complex therapy;

– relief of withdrawal syndrome in alcoholism with predominance of neurotic and vegetative-vascular disorders;

– acute intoxication with antipsychotic drugs;

– acute purulent inflammatory processes of the abdominal cavity (acute necrotizing pancreatitis, peritonitis) as part of complex therapy.

Active ingredient

Ethylmethylhydroxypyridine succinate

Composition

For 1 ml:

Active ingredient: ethylmethylhydroxypyridine succinate – 50.0 mg.

Excipients: sodium metabisulfite (sodium disulfite), water for injection.

How to take, the dosage

Intramuscularly or intravenously (by trickle or drip). When administering by infusion the drug should be diluted in 0.9% sodium chloride solution.

The dose is adjusted individually.

The drug is administered slowly over a period of 5-7 minutes by jetting at a rate of 40-60 drops per minute. The maximum daily dose should not exceed 1200 mg.

In acute disorders of cerebral circulation it is used in combination therapy in the first 10-14 days – intravenously drip 200-500 mg 2-4 times a day, then intramuscularly 200-250 mg 2-3 times a day for 2 weeks.

In case of craniocerebral trauma and consequences of craniocerebral injuries the drug is used for 10-15 days with intravenous drip 200-500 mg 2-4 times a day.

In patients with discirculatory encephalopathy in the decompensation phase the drug is used intravenously by shot or dropwise in the dosage of 200-500 mg 1-2 times daily during 14 days. Then intramuscularly 100-250 mg daily for the next two weeks.

For course prophylaxis of discirculatory encephalopathy it is administered intramuscularly in a dose of 200-250 mg 2 times a day for 10-14 days.

In cases of neurocirculatory dystonia, neurotic and neurosis-like conditions

The drug is administered intramuscularly with 50-400 mg daily for 14 days.

In mild cognitive impairment in elderly patients and in anxiety disorders, the drug is used intramuscularly in a dose of 100-300 mg per day for 14-30 days.

In acute myocardial infarction as part of complex therapy the drug is administered intravenously

or intramuscularly for 14 days, against standard therapy of myocardial infarction (including nitrates, beta-adrenoblockers, angiotensin-converting enzyme (ACE) inhibitors, thrombolytics, anticoagulant and antiaggregant agents, and symptomatic agents as indicated).

In the first 5 days for maximum effect the drug is administered intravenously, in the next 9 days the drug may be administered intramuscularly.

Intravenous administration of the drug is carried out by drop infusion, slowly (in order to avoid side effects) for 30-90 minutes (in 100-150 ml of 0.9% sodium chloride solution or 5% dextrose (glucose) solution), if necessary slow trickle intravenous administration of the drug for at least 5 minutes is possible.

The drug is administered (intravenously or intramuscularly) 3 times a day every 8 hours. The daily dose is 6-9 mg/kg of body weight, the single dose is 2-3 mg/kg of body weight. The maximum daily dose should not exceed 800 mg, a single dose is 250 mg.

In open angle glaucoma of various stages, as part of complex therapy, administer intramuscularly 100-300 mg per day, 1-3 times a day for 14 days.

In case of withdrawal alcohol syndrome the drug is administered intramuscularly or intravenously in a dose of 200-500 mg 2-3 times a day for 5-7 days.

In acute intoxication with antipsychotic drugs the drug is administered intravenously in a dose of 200-500 mg per day for 7-14 days.

In acute pyo-inflammatory processes of the abdominal cavity (acute necrotizing pancreatitis, peritonitis) the drug is administered in the first day both in the preoperative and in the postoperative period. Administered doses depend on the form and severity of the disease, process prevalence, variants of the clinical course. Withdrawal of the drug shall be carried out gradually only after steady positive clinical and laboratory effect.

In acute edematous (interstitial) pancreatitis the drug is prescribed 200-500 mg 3 times a day, intravenously by drip (in 0.9 % sodium chloride solution) and intramuscularly.

Mild degree of necrotic pancreatitis – 100-200 mg 3 times a day, by intravenous drip (in 0.9% sodium chloride solution) and intramuscularly. Moderate severity – 200 mg 3 times a day, intravenously drip (in 0.9% sodium chloride solution). A heavy course – in a dosage of 800 mg during the first day, twice a day; then 200-500 mg twice a day with a gradual reduction of the daily dose. Extremely severe course – in initial dosage of 800 mg daily until stable relief of pancreatogenic shock; after stabilization of condition – 300-500 mg 2 times a day by intravenous drip (in 0.9 % sodium chloride solution) with gradual decrease of daily dose.

Interaction

It enhances the effect of benzodiazepine anxiolytics, antiepileptic (carbamazepine), anti-Parkinsonian (levodopa) drugs.

Limits the toxic effects of ethanol.

Special Instructions

The drug is not prescribed to children under 18 years of age due to insufficient study of the drug action.

Impact on driving and operating ability

When using the drug, caution should be exercised while driving vehicles and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

Synopsis

Transparent, colorless or slightly yellowish solution.

Contraindications

– individual hypersensitivity to the drug;

– acute hepatic and/or renal failure;

– childhood;

– pregnancy;

– breastfeeding period – due to lack of efficacy and safety data.

With caution

Allergic diseases and reactions in the history.

Side effects

Gastrointestinal system disorders: nausea, dry mouth or metallic taste in the mouth, flatulence, diarrhea.

Nervous system disorders: drowsiness, failure to fall asleep.

Respiratory system disorders: sore throat, chest discomfort, feeling of shortness of breath (usually associated with excessive speed of administration and is short-lived).

Cardiovascular system: transient increase in blood pressure.

Others: allergic reactions, feeling of “spreading heat” throughout the body, unpleasant odor.

Overdose

Owing to its low toxicity, overdose is unlikely.

In accidental overdose, sleep disturbance (insomnia), in some cases drowsiness and sedation are possible. When administered intravenously, there may be an increase in blood pressure.

Treatment

It is usually not necessary – the symptoms disappear on their own within 24 hours. In particularly severe cases of insomnia, the use of one of the oral hypnotics and anxiolytics (nitrazepam 10 mg, oxazepam 10 mg, or diazepam 5 mg) is recommended. In case of excessive increase in blood pressure, hypotensive agents are used under control of blood pressure.

Pregnancy use

No teratogenic, mutagenic embryotoxic effects were found in experimental studies. Adequate and strictly controlled clinical studies in pregnancy and during breastfeeding have not been conducted. The drug is contraindicated during pregnancy and breastfeeding due to insufficient data on efficacy and safety of the drug during these periods.

Similarities

Mexidol, Mexifin, Mexiprim, Neurox, Medomexi, Mexicor, Evrin, Neuromexol