Emoden

APPROVED INSTRUCTION for medical use of the medicinal product EMOGEN (EMODEN)

Composition:

active substance: ethylmethylhydroxypyridine succinate;

1 ml of solution contains ethylmethylhydroxypyridine succinate 50 mg;

excipient: water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear solution, colorless to slightly yellow.

Pharmacotherapeutic group

Agents affecting the nervous system. ATC code N07X X.

Pharmacological Properties

Pharmacodynamics

Succinate of ethylmethylhydroxypyridine is an inhibitor of free radical processes, exerting membrane-protective, anti-hypoxic, stress-protective, nootropic, anticonvulsant, and anxiolytic effects. It enhances the body's resistance to various damaging factors, including oxygen-dependent pathological conditions (shock, hypoxia, ischemia, cerebrovascular disorders, alcohol intoxication, and intoxication with antipsychotic agents (neuroleptics)).

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

The mechanism of action of the drug is due to its anti-hypoxic, 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, gamma-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. It increases dopamine levels in the brain. It enhances compensatory activation of aerobic glycolysis and reduces the degree of inhibition 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.

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 zone, and reduces the consequences of reperfusion syndrome in acute coronary insufficiency. It enhances the antianginal activity of nitrate drugs. It 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

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. The drug rapidly transfers from the bloodstream into organs and tissues and is rapidly eliminated from the body. It is excreted primarily in urine in glucuronide-conjugated form, with insignificant amounts excreted unchanged.

Clinical Characteristics

Indications

• Acute cerebrovascular disorders;
• Traumatic brain injury, consequences of traumatic brain injury;
• 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 combination therapy;
• Primary open-angle glaucoma at various stages, as part of combination 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 combination therapy.

Contraindications

• Hypersensitivity to the active substance and/or to any of the excipients of the medicinal product.
• Acute hepatic or renal failure.
• Pregnancy.
• Breastfeeding period.
• Pediatric age.

Interaction with other medicinal products and other forms of interactions

When used concomitantly, the medicinal product enhances the effects of benzodiazepine anxiolytics, anticonvulsants (carbamazepine), anti-Parkinson agents (levodopa), and reduces the toxic effect of ethanol. It increases the antianginal activity of nitro-compounds 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 for use

The degree of restrictions is determined by individual intolerance to the drug. The drug 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.

Use during pregnancy or breastfeeding

Pregnancy. There are no data available on the use of ethylmethylhydroxypyridine succinate in pregnant women. Reproductive toxicity studies in animals do not indicate the presence of direct or harmful effects. The drug is contraindicated during pregnancy.

Breastfeeding. There is no information available on the passage of ethylmethylhydroxypyridine succinate (or its metabolites) into human breast milk. The drug is contraindicated during lactation.

Fertility. Animal reproductive toxicity studies do not indicate the presence of reproductive toxicity.

Ability to influence the reaction rate when driving or operating machinery

During treatment with the drug, caution should be exercised in activities requiring rapid psychomotor reactions (e.g., driving vehicles or operating machinery).

Administration and Dosage

Administration method

The medicinal product Emoden is intended for intramuscular or intravenous (bolus or infusion) administration.

For infusion administration, Emoden should be diluted in 100–150 mL of sodium chloride physiological solution or 5% glucose solution.

For bolus administration, the medicinal product should be administered slowly over 5–7 minutes; for infusion, at a rate of 40–60 drops per minute.

The maximum daily dose must not exceed 1200 mg.

Dosage

Acute cerebrovascular disorders

The medicinal product should be administered intravenously by infusion at a dose of 200–500 mg 2–4 times daily for the first 10–14 days, followed by intramuscular administration at a dose of 200–250 mg 2–3 times daily for the subsequent 14 days.

Traumatic brain injury, consequences of traumatic brain injury

The medicinal product should be administered intravenously by infusion at a dose of 200–500 mg 2–4 times daily for 10–15 days.

Disruptive encephalopathy

Decompensation phase – the medicinal product should be administered intravenously either as bolus or infusion at a dose of 200–500 mg 1–2 times daily for the first 14 days, followed by intramuscular administration at a dose of 100–250 mg daily for the subsequent 14 days.

Course prophylaxis – the medicinal product should be administered intramuscularly at a dose of 200–250 mg twice daily for 10–14 days.

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

Mild (moderate) cognitive disorders in elderly patients and anxiety states. The medicinal product should be administered intramuscularly at a dose of 100–300 mg daily for 14–30 days.

Acute myocardial infarction, as part of combination therapy

The medicinal product Emoden should be administered intravenously or intramuscularly for 14 days alongside conventional myocardial infarction therapy, including nitrates, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, thrombolytics, anticoagulant and antiplatelet agents, as well as symptomatic treatments as indicated.

For the first 5 days, to achieve maximum effect, intravenous administration is recommended; for the subsequent 9 days, intramuscular administration of Emoden is possible. Intravenous administration should be performed via slow infusion (to avoid adverse reactions) 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 administration over at least 5 minutes is possible.

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

Open-angle glaucoma at various stages, as part of combination therapy

The medicinal product should be administered intramuscularly at a dose of 100–300 mg 1–3 times daily for 14 days.

Alcohol withdrawal syndrome

The medicinal product should be administered intravenously by infusion or intramuscularly at a dose of 200–500 mg 2–3 times daily for 5–7 days.

Acute intoxication with antipsychotic agents

The medicinal product should be administered intravenously at a dose of 200–500 mg daily for 7–14 days.

Acute purulent-inflammatory processes in the abdominal cavity (acute necrotic pancreatitis, peritonitis), as part of combination therapy

In acute purulent-inflammatory processes of the abdominal cavity (acute necrotic pancreatitis, peritonitis), Emoden 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 variants. Discontinuation of Emoden should be gradual and only after a sustained positive clinical and laboratory effect.

Acute edematous (interstitial) pancreatitis – the medicinal product Emoden should be administered intravenously by infusion (in isotonic sodium chloride solution) and intramuscularly at a dose of 200–500 mg 3 times daily.

Mild course of necrotic pancreatitis – the medicinal product Emoden should be administered intravenously by infusion (in isotonic sodium chloride solution) and intramuscularly at a dose of 100–200 mg 3 times daily.

Moderate severity course of necrotic pancreatitis – the medicinal product should be administered intravenously by infusion (in isotonic sodium chloride solution) and intramuscularly at a dose of 200 mg 3 times daily.

Severe course of necrotic pancreatitis – the medicinal product should be administered in pulse dosing: 800 mg on the first day with twice-daily administration; thereafter, at a dose of 200–500 mg twice daily, with gradual reduction of the daily dose.

Very severe course of necrotic pancreatitis – the medicinal product should be administered intravenously by infusion (in isotonic sodium chloride solution) at an initial dose of 800 mg daily until sustained resolution of pancreatogenic shock; after stabilization of the patient's condition, at a dose of 300–500 mg twice daily.

Children

Controlled clinical studies on the safety of Emoden in children have not been conducted; therefore, its use is contraindicated in this patient population.

Overdose

Symptoms: drowsiness, insomnia.

Treatment: due to low toxicity, overdose is unlikely. Treatment is generally not required, and symptoms resolve spontaneously within several days. In cases of pronounced overdose symptoms, symptomatic and supportive therapy should be administered.

Side effects

To avoid the development of adverse reactions, the dosage regimen and rate of administration of the medicinal product should be strictly observed.

Criteria for assessing the frequency of adverse reactions: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).

Immune system disorders:

very rare – anaphylactic shock, angioneurotic edema, urticaria;

frequency not known – allergic reactions, hyperemia, possible severe hypersensitivity reactions.

Psychiatric disorders:

very rare – drowsiness;

frequency not known – sleep disturbances, anxiety, emotional reactivity.

Nervous system disorders:

very rare – headache, dizziness (which may be related to too rapid administration and is transient);

frequency not known – coordination disorders, tremor.

Cardiac disorders:

very rare – decreased blood pressure, increased blood pressure (which may be related to too rapid administration and is transient);

frequency not known – palpitations, tachycardia.

Respiratory, thoracic and mediastinal disorders:

very rare – dry cough, throat irritation, chest discomfort, breathing difficulty (which may be related to too rapid administration and is 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 – itching, rash, urticaria, 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.

During 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 medicinal product registration is important. 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, are encouraged to report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions

Store at a temperature not exceeding 30 °C in the original packaging. Keep out of reach of children.

Incompatibility

The medicinal product should not be mixed with other drugs or medicinal products. Only use solvents specified in the instructions.

Packaging

2 ml in an ampoule, 5 ampoules in a blister, 1 or 2 blisters per cardboard box.

5 ml in an ampoule, 5 ampoules in a blister, 1 or 2 blisters per cardboard box.

Prescription category. Prescription only.

Manufacturer

Abhil Laboratories Private Limited.

Manufacturer's address and place of business

Village Bhagwanpur, Tehsil Dera Bassi, District Sahibzada Ajit Singh Nagar, Punjab – 140507, India.