Pervagor

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

Composition:

Active substance: ethylmethylhydroxypyridine succinate;

1 ml of solution contains ethylmethylhydroxypyridine succinate equivalent to 100% substance 50 mg;

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

Pharmaceutical form. Injection solution.

Main physicochemical properties: colorless or slightly yellowish clear liquid.

Pharmacotherapeutic group. Agents affecting the nervous system.

ATC code N07X X.

Pharmacological properties.

Pharmacodynamics.

PERVAGOR 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 blood cell membrane structures (erythrocytes and platelets) during hemolysis. PERVAGOR exerts a hypolipidemic effect, reducing total cholesterol and low-density lipoprotein levels. 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 properties. It inhibits lipid peroxidation, increases superoxide dismutase activity, improves the lipid-to-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 ability to bind ligands, supporting the structural and functional organization of biomembranes, neurotransmitter transport, and improving synaptic transmission. The drug 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 electrical activity and myocardial contractility, increases coronary blood flow in the ischemic area, reduces consequences of reperfusion syndrome in acute coronary insufficiency, and enhances the antianginal activity of nitrate drugs. PERVAGOR 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 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. PERVAGOR rapidly transfers from the bloodstream into organs and tissues and is quickly eliminated from the body. The drug is excreted in urine, mainly in glucuronide-conjugated form, and in small amounts unchanged.

Clinical characteristics.

Indications.

Acute cerebrovascular disorders;

Traumatic brain injury, consequences of traumatic brain injuries;

Dyscirculatory encephalopathy;

Vegetative-vascular dystonia syndrome;

Mild cognitive disorders of atherosclerotic origin;

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;

Management of alcohol withdrawal syndrome with predominant neurosis-like 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 period.

Interaction with other medicinal products and other types of interactions.

PERVAGOR enhances the effect of benzodiazepine anxiolytics, anticonvulsants (carbamazepine), antiparkinsonian agents (levodopa). Reduces the toxic effect of ethyl alcohol.

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 therapeutic effect achieved, continuation of treatment with the drug orally in tablet form is recommended.

Use during pregnancy or breastfeeding.

The medicinal product is contraindicated during pregnancy and breastfeeding.

Ability to influence reaction rate when driving or operating machinery.

During treatment, caution is necessary when driving or operating complex machinery, taking into account the possible occurrence of adverse effects that may affect reaction speed and the ability to concentrate.

Method of Administration and Dosage.

The medicinal product 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 therapeutic effect is achieved. PERVAGOR is administered by bolus injection slowly over 5–7 minutes, and by infusion at a rate of 40–60 drops per minute. The maximum daily dose should not exceed 1200 mg.

In acute cerebral circulation disorders, the drug is prescribed as part of combination therapy for adults during the first 2–4 days by intravenous bolus or 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 consequences, the drug PERVAGOR is used for 10–15 days by intravenous infusion at 200–500 mg 2–4 times daily.

In decompensated phase of dyscirculatory encephalopathy, the drug 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 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 a dose of 100–300 mg daily for 14–30 days.

In acute myocardial infarction, PERVAGOR is administered intravenously or intramuscularly for 14 days as part of conventional therapy for myocardial infarction, including nitrates, beta-adrenoblockers, angiotensin-converting enzyme (ACE) inhibitors, thrombolytics, anticoagulant and antiaggregant agents, as well as symptomatic treatment as indicated. Intravenous administration of PERVAGOR is preferred during the first 5 days to achieve maximum effect; during the following 9 days, intramuscular administration is possible. Intravenous administration of the drug is performed by drip infusion slowly (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 PERVAGOR is possible over no less than 5 minutes.

Administration of the drug (intravenous or intramuscular) is performed 3 times daily every 8 hours. The daily therapeutic dose is 6–9 mg per kilogram of body weight, the single dose being 2–3 mg/kg. The maximum daily dose should not exceed 800 mg, and the single dose should not exceed 250 mg.

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

In alcohol withdrawal syndrome, the drug is administered 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 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 necrotizing pancreatitis, peritonitis), the drug is prescribed on the first day both in the preoperative and postoperative periods. 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 effect is achieved.

In acute edematous (interstitial) pancreatitis, PERVAGOR 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 with two administrations, followed by 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 symptoms; after stabilization of the patient’s condition, 300–500 mg twice daily by intravenous infusion (with isotonic sodium chloride solution) with gradual reduction of the daily dose.

Children.

Well-controlled clinical studies on the safety of the drug in children have not been conducted; therefore, its use 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 adverse reactions, it is recommended to adhere to the recommended dosage regimen and rate of administration. The frequency of adverse reactions 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 (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 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 – decreased blood pressure, increased blood pressure (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.

With 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 the reach of children.

Incompatibilities.

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

Packaging.

2 ml in an ampoule; 5 ampoules in a blister, 2 blisters per carton.

Prescription status.

Prescription only.

Manufacturer.

Private Joint-Stock Company "Lekhim-Kharkiv".

Manufacturer's address and place of business.

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