Zamexen

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ZAMEXEN (ZAMEXEN)

Composition:

Active substance: ethylmethylhydroxypyridine succinate;

1 ml of solution contains ethylmethylhydroxypyridine succinate 50 mg;

Excipients: sodium metabisulfite (E 223), water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: colorless or slightly yellowish clear liquid.

Pharmacotherapeutic group. Agents affecting the nervous system.

ATC code N07X X.

Pharmacological Properties.

Pharmacodynamics.

Zamexen 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 oxygen-dependent pathological conditions (shock, hypoxia and ischemia, impaired cerebral circulation, alcohol intoxication, and intoxication with antipsychotic agents (neuroleptics)).

Zamexen 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. The drug exerts a hypolipidemic effect, reducing total cholesterol and low-density lipoprotein (LDL) levels. It decreases 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 increases 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 ligand-binding capacity, promoting preservation of the structural-functional organization of biomembranes, neurotransmitter transport, and improving synaptic transmission. Zamexen 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, activates mitochondrial energy-synthesizing functions, and stabilizes cellular membranes.

Zamexen normalizes metabolic processes in ischemic myocardium, reduces the area of necrosis, restores and improves electrical activity and myocardial contractility, increases coronary blood flow in the ischemic area, and reduces the consequences of reperfusion syndrome in acute coronary insufficiency. It enhances the antianginal activity of nitro compounds. Zamexen 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 and increases visual acuity.

Pharmacokinetics.

After intramuscular administration, the drug is detectable in plasma for up to 4 hours after injection. 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. Zamexen rapidly transfers from the bloodstream into organs and tissues and is quickly 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;

Vegetative-vascular dystonia;

Mild cognitive impairments of atherosclerotic origin;

Anxiety disorders in neurotic and neurasthenic 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;

Management of alcohol withdrawal syndrome with predominance of neurasthenic and vegetative-vascular disorders;

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 drug, childhood, pregnancy, breastfeeding.

Interaction with other medicinal products and other forms of interactions.

Zamexen enhances the effect of benzodiazepine anxiolytics, anticonvulsants (carbamazepine), antiparkinsonian agents (levodopa); reduces the toxic effect of ethanol.

Special precautions for use.

In individual cases, especially in predisposed patients or in patients with bronchial asthma and hypersensitivity to sulfites, severe hypersensitivity reactions may occur.

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

Extreme caution is required when administering to patients with diabetic retinopathy (treatment course should not exceed 7–10 days) due to its potential to enhance proliferative processes.

After completion of parenteral administration, to maintain the achieved therapeutic effect, continuation of treatment with the drug in oral tablet form is recommended.

Use during pregnancy or breastfeeding.

Zamexen is contraindicated during pregnancy and breastfeeding.

Ability to affect reaction rate when driving or operating machinery.

During treatment, caution is advised when driving or operating complex machinery, taking into account the possibility of adverse effects that may influence reaction speed and concentration ability.

Method of Administration and Dosage

Zamexen is administered intramuscularly or intravenously (by bolus injection or infusion). Dosages are individually adjusted. When administered by infusion, the drug should be diluted in 200 ml of sodium chloride physiological solution. 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. Bolus injections of Zamexen should be administered slowly over 5–7 minutes; infusion should be performed at a rate of 40–60 drops per minute. The maximum daily dose must not exceed 1200 mg.

In acute cerebrovascular disorders, Zamexen is used as part of combination therapy in adults during the first 2–4 days, administered intravenously either as a bolus or by infusion at 200–500 mg once daily, followed by intramuscular administration of 200–500 mg 2–3 times daily. The treatment duration is 14 days.

In traumatic brain injury and its sequelae, Zamexen is administered intravenously by infusion at 200–500 mg 2–4 times daily for 10–15 days.

In decompensated phase of dyscirculatory encephalopathy, Zamexen should be administered intravenously either as a bolus or by infusion at 200–500 mg 1–2 times daily for 14 days. Subsequently, the drug is administered intramuscularly at 100–250 mg daily for the following 2 weeks.

For course prophylaxis of dyscirculatory encephalopathy, the drug is administered intramuscularly to adults at 200–250 mg twice daily for 10–14 days.

In mild cognitive disorders in elderly patients and in anxiety states, the drug is administered intramuscularly at 100–300 mg daily for 14–30 days.

In acute myocardial infarction, Zamexen is administered intravenously or intramuscularly for 14 days as an adjunct to conventional myocardial infarction therapy, including nitrates, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, thrombolytics, anticoagulants, antiplatelet agents, and symptomatic treatments as indicated. For maximum efficacy during the first 5 days, intravenous administration of Zamexen is recommended; for the subsequent 9 days, intramuscular administration may be used. Intravenous administration of Zamexen is performed by slow 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 Zamexen may be administered over at least 5 minutes.

Zamexen (either intravenous or intramuscular) is administered 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; the maximum single dose must not exceed 250 mg.

In various stages of open-angle glaucoma, Zamexen is used as part of combination therapy, administered intramuscularly at 100–300 mg daily, 1–3 times daily, for 14 days.

In alcohol withdrawal syndrome, Zamexen is administered at a dose of 200–500 mg intravenously or intramuscularly 2–3 times daily, or by intravenous infusion 1–2 times daily for 5–7 days.

In acute intoxication with antipsychotic agents, the drug is administered intravenously to adults 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 is prescribed on the first day both pre- and post-operatively. Dosages 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, Zamexen is prescribed to adults at 200–500 mg 3 times daily by intravenous infusion (with isotonic sodium chloride solution) and intramuscularly.

• Mild severity: 100–200 mg 3 times daily by intravenous infusion (with isotonic sodium chloride solution) and intramuscularly.
• Moderate severity: 200 mg 3 times daily by intravenous infusion (with isotonic sodium chloride solution) in adults.
• Severe course: pulse-dose regimen of 800 mg on the first day administered twice; thereafter, 200–500 mg twice daily with gradual reduction of the daily dose.
• Very severe course: initial dose of 800 mg daily until stable control of pancreatogenic shock is achieved; after stabilization, 300–500 mg twice daily by intravenous infusion (with isotonic sodium chloride solution), with gradual reduction of the daily dose.

Children

No well-controlled clinical studies on the safety of the drug in children have been conducted; therefore, Zamexen is contraindicated in this patient population.

Overdose

Symptoms: drowsiness, insomnia.

Treatment: due to the low toxicity of the drug, overdose is unlikely. Treatment is usually not required; symptoms resolve spontaneously within 24 hours. In cases of pronounced symptoms, supportive and symptomatic therapy is administered.

Adverse Reactions.

To avoid the occurrence of adverse reactions, it is recommended to follow the prescribed 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 determined 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 transient in nature); frequency not known – coordination disturbances, tremor.

Vascular disorders: very rare – hypotension, hypertension (may be related to excessively high infusion rate and is transient in nature).

Respiratory, thoracic and mediastinal disorders: very rare – dry cough, throat irritation, chest discomfort, dyspnea (may be related to excessively high infusion rate and is transient in nature); frequency not known – bronchospasm.

Gastrointestinal disorders: very rare – dry mouth, nausea, unpleasant taste sensation, metallic taste in the mouth; 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.

During prolonged administration of the drug, the following adverse effects may occur: flatulence, weakness, peripheral edema.

Shelf life.

2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Incompatibilities.

The drug should not be mixed with other medicinal products. Use only the solvents specified in the instructions.

Packaging. 2 ml in an ampoule; 10 ampoules per pack or 5 ampoules in a blister, 2 blisters per pack. 5 ml in an ampoule; 5 ampoules per pack or 5 ampoules in a blister, 1 blister per pack.

Prescription status.

Prescription only.

Manufacturer.

Private Joint-Stock Company "Lekhym-Kharkiv".

Manufacturer's address and location of business activity.

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