Evrin, 50 mg/ml 2 ml 10 pcs

An antioxidant agent.

ATX code:

N07XX.

Pharmacological properties

Pharmacodynamics

Ethylmethylhydroxypyridine succinate belongs to the class of 3-oxypyridines, 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, gamma-aminobutyrate, 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 increase of adenosine triphosphate (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, cerebral circulatory disorders, 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.

Maintains 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 the 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 failure.

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.

Stabilizes blood cell membranes (erythrocytes and platelets), reducing the likelihood of hemolysis. It has a hypolipidemic effect by reducing the content of total cholesterol and low-density lipoproteins.

Pharmacokinetics

In absorption

In single and repeated administration the maximum concentration (Cmax) in plasma is reached after 0.58 h. When administered in dose of 400-500 mg the Cmax in plasma is 3.5-4 mcg/ml.

Distribution

It is 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 were identified: 3-oxypyridine phosphate – formed in the liver and with the help of alkaline phosphatase breaks down into phosphoric acid and 3-oxypyridine; the 2nd metabolite – pharmacologically active, formed in large amounts and found in the urine 1-2 days after administration; the 3rd – excreted in large amounts in the urine; the 4th and 5th – glucuronconjugates.

Elimation

Extracted from the blood plasma rapidly and practically 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 – unchanged (0.3% in 12 hours). Rates of urinary excretion of unchanged ethylmethylhydroxypyridine succinate and metabolites have individual variability.

Indications

• acute disorders of cerebral circulation (as part of complex therapy);
• cranial trauma, consequences of craniocerebral injuries;
• dyscirculatory encephalopathy;
• syndrome of vegetative (neurocirculatory) dystonia;
• mild cognitive disorders of atherosclerotic genesis;
• anxiety disorders in neurotic and neurosis-like states;
• acute myocardial infarction (from the first day) as part of the treatment;
• primary open-angle glaucoma of various stages, as a part of the complex therapy;
• curing the withdrawal syndrome in alcoholism with the prevalence of neurosis-like and vegetative-vascular disorders;
• acute intoxication with antipsychotic medicines;
• acute purulent inflammatory processes of the abdominal cavity (acute necrotizing pancreatitis, peritonitis) as a part of the complex therapy.

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Active ingredient

Ethylmethylhydroxypyridine succinate

Composition

1 ml of the drug contains:

Active ingredient:

Ethylmethylhydroxypyridine succinate 50.0 mg,

Excipients:

Sodium disulfite 0.47 mg,

Water for injection up to 1.0 ml.

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.

Doses are adjusted individually.

Jet is administered slowly for 5-7 minutes, drip – at a rate of 40-60 drops per minute. The maximum daily dose should not exceed 1,200 mg.

In case of acute disturbances of cerebral circulation it is used in combination therapy in the first 10-14 days – intravenously by drip 200-500 mg 2-4 times daily, then intramuscularly 200-250 mg 2-3 times daily during 2 weeks.

In case of traumatic brain injury and after-effects the drug is administered for 10-15 days by intravenous drip 200-500 mg 2-4 times a day.

In case of dyscirculatory encephalopathy in the decompensation phase the drug is administered intravenously by trickle or drip doses of 200-500 mg 1-2 times a day for 14 days. Then the preparation is administered intramuscularly in dosage of 100-250 mg per day during the next two weeks.

For course prophylaxis of disirculatory encephalopathy the preparation is administered intramuscularly in dosage 200-250 mg twice a day during 10-14 days.

In cases of neurocirculatory dystonia, neurotic and neurosis-like conditions the preparation is administered intramuscularly 50-400 mg per day for 14 days.

In mild cognitive disorders in elderly patients and in cases of anxiety disorders the preparation is administered intramuscularly in dose 100-300 mg per day for 14-30 days.

In acute myocardial infarction within complex therapy the drug is administered intravenously or intramuscularly within 14 days against standard therapy of myocardial infarction (including nitrates, beta-adrenoblockers, angiotensin-converting enzyme inhibitors (ACE), thrombolytics, anticoagulants and antiplatelet agents and symptomatic drugs by prescription).

During the first 5 days the drug shall be administered intravenously to achieve maximum effect, during the following 9 days the drug may be administered intramuscularly. The drug is administered intravenously by drop infusion, slowly (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, the drug can be slowly injected for at least 5 minutes. 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 – 250 mg.

In open-angle glaucoma of different stages the drug is administered intramuscularly 100-300 mg per day 1 to 3 times a day for 14 days as part of the treatment.

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

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

In acute pyo-inflammatory processes of abdominal cavity (acute necrotizing pancreatitis, peritonitis) the drug is prescribed in the first day after surgery as well as during the post-surgical period. Administered doses depend on the form and severity of the disease, process prevalence, variants of the clinical course. The drug shall be discontinued only after the sustained positive clinical and laboratory effect.

In acute interstitial pancreatitis the drug is administered by 200-500 mg three times a day by intravenous drip (in 0.9% sodium chloride solution) and intramuscularly.

Mild degree of necrotic pancreatitis – 100-200 mg three times a day, i.v. dropwise (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 severe 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, 300-500 mg 2 times daily by intravenous drip (in 0.9% sodium chloride solution) with gradual reduction of daily dosage.

Interaction

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

Influence 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.

Contraindications

• high sensitivity to the drug
• acute hepatic and/or renal failure
• childhood;
• Pregnancy
• Breast-feeding period – due to lack of efficacy and safety data.

Cautions

Allergic diseases in the history.

Side effects

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

Nervous system: drowsiness, difficulty falling asleep.

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

Cardiovascular system: transient increase in blood pressure.

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

Overdose

Due to low toxicity, overdose is unlikely. In case of accidental overdose sleep disturbance (insomnia), in some cases drowsiness and sedation are possible. At intravenous injection blood pressure may increase.

Treatment

As a rule, it is not required – symptoms disappear on their own within a day. In particularly severe cases of insomnia, the use of one of the sleeping pills and anxiolytics for oral administration (nitrazepam 10 mg, oxazepam 10 mg or diazepam 5 mg) is recommended. In case of excessive increase in blood pressure – hypotensive drugs 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 lactation have not been conducted.

The drug is contraindicated in pregnancy and lactation due to insufficient data on the effectiveness and safety of the drug in these periods.

Similarities

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