Lodixem

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

Composition:

Active substance: ethylmethylhydroxypyridine succinate;

1 ml of solution contains ethylmethylhydroxypyridine succinate 50.0 mg;

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

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear colorless or slightly yellowish liquid.

Pharmacotherapeutic group. Agents affecting the nervous system.

ATC Code N07X X.

Pharmacological Properties

Pharmacodynamics

Lodixem is an inhibitor of free radical processes and a membrane protector, exerting anti-hypoxic, stress-protective, nootropic, anticonvulsant, and anxiolytic effects. The medicinal product enhances the body's resistance to various damaging factors, particularly oxygen-dependent pathological conditions (shock, hypoxia and ischemia, cerebral circulation disorders, alcohol intoxication, and intoxication with antipsychotic agents (neuroleptics)).

The medicinal product Lodixem improves cerebral metabolism and cerebral blood supply, microcirculation, and blood rheological properties, and reduces platelet aggregation. It stabilizes blood cell membranes (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 Lodixem is due to its anti-hypoxic, antioxidant, and membrane-protective effects. It inhibits lipid peroxidation, increases superoxide dismutase activity, increases 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 improved synaptic transmission. The medicinal product Lodixem 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, resulting in increased levels of adenosine triphosphate (ATP) and creatine phosphate, activation of mitochondrial energy-synthesizing functions, and stabilization of cellular membranes.

The medicinal product Lodixem 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. Lodixem helps preserve 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 optic nerve, thereby increasing visual acuity.

Pharmacokinetics

After intramuscular administration, the medicinal product Lodixem is detectable in blood plasma for up to 4 hours post-administration. The time to reach maximum concentration is 0.45–0.5 hours. Maximum plasma concentration at doses of 400–500 mg is 3.5–4.0 μg/mL. Lodixem rapidly transfers from the bloodstream into organs and tissues and is rapidly eliminated from the body. The drug is excreted primarily in urine, mainly as glucuronide conjugates, and to a minor extent unchanged.

Clinical characteristics.

Indications.

• Acute cerebrovascular disorders;
• Traumatic brain injury, consequences of traumatic brain injury;
• Dyscirculatory encephalopathy;
• Neurocirculatory dystonia;
• Mild cognitive impairment 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 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 complex therapy.

Contraindications.

Hypersensitivity to the active substance and/or to excipients of the medicinal product Lodycsem.

Acute hepatic or renal failure.

Paediatric use.

Pregnancy, lactation period.

Interaction with other medicinal products and other forms of interactions.

When used concomitantly, the medicinal product Lodycsem enhances the effect of benzodiazepine anxiolytics, anticonvulsants (carbamazepine), antiparkinsonian agents (levodopa). Reduces the toxic effect of ethanol.

Special precautions for use.

The extent of restrictions is determined by individual intolerance to the medicinal product Lodixem.

The product contains sodium metabisulfite, which may rarely cause hypersensitivity reactions and bronchospasm.

Lodixem contains:

0.011 mmol (or 242 µg) of sodium in 1 ml of the medicinal product;

0.264 mmol (or 5.808 mg) of sodium in 24 ml of the medicinal product. This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e. it is practically sodium-free.

Use during pregnancy or breastfeeding.

Well-controlled clinical studies on the safety of using the drug during pregnancy and breastfeeding have not been conducted; therefore, the medicinal product Lodixem is contraindicated during pregnancy and breastfeeding.

Ability to influence reaction rate when driving or operating machinery.

During treatment, caution is required when driving vehicles or operating complex machinery, due to the potential for adverse reactions that may affect reaction speed and the ability to concentrate.

Method of Administration and Dosage

The medicinal product Lodicsem is administered intramuscularly or intravenously (by bolus injection or infusion). Dosages are individually adjusted. When administered by infusion, the medicinal product should be diluted in 200 ml of 0.9% sodium chloride solution. Intravenous bolus injection of Lodicsem should be performed slowly over 5–7 minutes; infusion should be administered at a rate of 40–60 drops per minute. The maximum daily dose should not exceed 1200 mg.

In acute cerebral circulation disorders: Lodicsem is used as part of combination therapy during the first 10–14 days, administered intravenously by infusion to adults at 200–500 mg 2–4 times daily, followed by intramuscular administration of 200–250 mg 2–3 times daily for the next 2 weeks.

In traumatic brain injury and its sequelae: Lodicsem is administered intravenously by infusion over 10–15 days at a dose of 200–500 mg 2–4 times daily.

In decompensated phase of dyscirculatory encephalopathy: Lodicsem should be administered intravenously either by bolus injection or infusion at a dose of 200–500 mg 1–2 times daily for the first 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 impairment in elderly patients and anxiety states: the drug is administered intramuscularly at a dose of 100–300 mg daily for 14–30 days.

In acute myocardial infarction as part of combination therapy: Lodicsem is administered intravenously or intramuscularly for 14 days alongside conventional myocardial infarction therapy, including nitrates, beta-adrenoblockers, angiotensin-converting enzyme (ACE) inhibitors, thrombolytics, anticoagulant and antiplatelet agents, as well as symptomatic treatments as indicated. Intravenous administration is recommended during the first 5 days to achieve maximum effect; intramuscular administration may be used during the subsequent 9 days. Intravenous administration should be performed as a 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 injection may be performed over no less than 5 minutes.

Administration of Lodicsem (intravenous or intramuscular) should be performed 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 should not exceed 800 mg; the maximum single dose should not exceed 250 mg.

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

In alcohol withdrawal syndrome: Lodicsem is administered at a dose of 200–500 mg intravenously by infusion 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 conditions of the abdominal cavity (acute necrotic pancreatitis, peritonitis) as part of combination therapy: the drug is prescribed on the first day both preoperatively and postoperatively. Dosages depend on the form and severity of the disease, extent of the process, and clinical presentation. Discontinuation of the drug should be gradual and only after a sustained positive clinical and laboratory response.

In acute edematous (interstitial) pancreatitis: Lodicsem is prescribed to adults at 200–500 mg 3 times daily by intravenous infusion (in isotonic sodium chloride solution) and intramuscularly. Mild necrotizing pancreatitis: 100–200 mg 3 times daily by intravenous infusion (in isotonic sodium chloride solution) and intramuscularly. Moderate severity: 200 mg 3 times daily by intravenous infusion (in isotonic sodium chloride solution) to adults. Severe course: pulse-dose regimen of 800 mg on the first day administered twice, 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 is achieved; after stabilization, 300–500 mg twice daily by intravenous infusion (in isotonic sodium chloride solution) with gradual reduction of the daily dose.

Children.

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

Overdose.

Overdose may cause somnolence or insomnia.

Treatment of overdose.

Due to the low toxicity of the drug, overdose is unlikely. Usually, no specific treatment is required, and symptoms resolve spontaneously within several days. In cases of pronounced overdose symptoms, symptomatic and supportive therapy should be administered.

Adverse reactions.

To avoid the development of adverse reactions, the dosing regimen and rate of administration of the medicinal product Lodixem should be strictly followed.

The information on adverse reactions provided below is classified by organ systems and frequency of occurrence. Frequencies are categorized as follows: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10,000 and <1/1000), very rare (<1/10,000), including isolated cases, and frequency not known (cannot be estimated from available data).

Immune system disorders:

Very rare – anaphylactic shock, angioedema, urticaria.

Psychiatric disorders:

Very rare – somnolence.

Nervous system disorders:

Very rare – headache, dizziness (which may be related to excessively rapid administration and is transient).

Vascular disorders:

Very rare – decrease in blood pressure, increase in blood pressure (which may be related to excessively rapid administration and is transient).

Respiratory, thoracic and mediastinal disorders:

Very rare – dry cough, throat irritation, chest discomfort, dyspnea (which may be related to excessively rapid administration and is transient).

Gastrointestinal disorders:

Very rare – dry mouth, nausea, sensation of unpleasant odor, metallic taste in the mouth.

Skin and subcutaneous tissue disorders:

Very rare – pruritus, rash, hyperemia.

General disorders and administration site conditions:

Very rare – sensation of warmth.

Reporting of adverse reactions

Reporting of adverse reactions following medicinal product registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua

Shelf life. 2 years.

Storage conditions.

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

Packaging. 2 ml in 5 ampoules in a blister pack; 2 blisters per carton box;

5 ml in 5 ampoules in a blister pack; 1 blister per carton box.

Prescription status. Prescription only.

Manufacturer/Applicant. LLC "Yuria-Pharm".

Manufacturer's address and place of business.

108, Kobzarska Street, Cherkasy, Cherkasy Oblast, 18030, Ukraine. Tel.: (044) 281-01-01.