Neuralon

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

Composition:

Active substances: thiamine hydrochloride, pyridoxine hydrochloride, cyanocobalamin;

1 ml of solution contains 50 mg thiamine hydrochloride, 50 mg pyridoxine hydrochloride, 500 mcg cyanocobalamin;

Excipients: lidocaine hydrochloride, benzyl alcohol, potassium hexacyanoferrate (III), sodium hexametaphosphate, sodium hydroxide solution, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical characteristics: clear, dark red solution.

Pharmacotherapeutic group.

Vitamin B1 preparations in combination with vitamin B6 and/or vitamin B12. ATC code A11D B.

Pharmacological Properties

Pharmacodynamics

Neurotropic vitamins of the B group exert beneficial effects in inflammatory and degenerative diseases of nerves and the musculoskeletal system. In high doses, they possess analgesic properties, promote improved circulation, and help normalize nervous system function and hematopoiesis. B-complex vitamins are also used to correct deficiency states.

Thiamine (vitamin B1) is a highly important active substance. In the body, it is phosphorylated to form the biologically active compounds thiamine diphosphate (cocarboxylase) and thiamine triphosphate (TTP). Thiamine diphosphate acts as a coenzyme in key carbohydrate metabolism processes, which are crucial for metabolic functions in nervous tissue and influence nerve impulse conduction in synapses. In vitamin B1 deficiency, metabolites accumulate in tissues—primarily lactic acid and pyruvic acid—leading to various pathological conditions and disturbances in nervous system function.

Pyridoxine (vitamin B6), in its phosphorylated form (pyridoxal-5’-phosphate, PLP), serves as a coenzyme for several enzymes involved in general non-oxidative amino acid metabolism. Through decarboxylation, these enzymes contribute to the formation of physiologically active amines (e.g., adrenaline, histamine, serotonin, dopamine, tyramine). Through transamination, they participate in anabolic and catabolic metabolic processes (e.g., glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, γ-aminobutyric acid, α-ketoglutarate transaminase), as well as in various amino acid synthesis and degradation pathways. Vitamin B6 influences four distinct steps in tryptophan metabolism. In hemoglobin synthesis, it catalyzes the formation of α-amino-β-keto-adipic acid.

Cyanocobalamin (vitamin B12) is essential for cellular metabolism. It affects hematopoietic function (as an extrinsic anti-anemic factor), participates in the synthesis of choline, methionine, creatinine, and nucleic acids, and exerts analgesic effects.

Pharmacokinetics

After parenteral administration, vitamin B1 is distributed throughout the body. Approximately 1 mg of thiamine is metabolized daily. Metabolites are excreted in urine. Defosphorylation occurs in the kidneys. The biological half-life of thiamine is 0.35 hours. Accumulation of vitamin B1 in the body does not occur due to its limited lipid solubility.

After parenteral administration, vitamin B6 is phosphorylated and oxidized to pyridoxal-5-phosphate. In blood plasma, pyridoxal-5-phosphate and pyridoxal are bound to albumin. The transport form is pyridoxal. To cross the cell membrane, pyridoxal-5-phosphate bound to albumin is hydrolyzed by alkaline phosphatase into pyridoxal.

Vitamin B12, after parenteral administration, forms transport protein complexes that are rapidly absorbed by the liver, bone marrow, and other proliferative tissues. It enters bile and participates in enterohepatic circulation and crosses the placenta.

Clinical characteristics.

Indications.

Systemic neurological disorders caused by a confirmed deficiency of vitamins B1, B6, and B12, when they cannot be corrected by dietary intake.

Contraindications.

• Hypersensitivity to the active substances or to any of the excipients;
• acute impairment of cardiac conduction;
• acute decompensated heart failure;
• pregnancy;
• breastfeeding;
• due to the presence of vitamin B1 in the formulation: allergic reactions;
• due to the presence of vitamin B6 in the formulation: peptic ulcer of the stomach and duodenum in the acute phase — since increased gastric juice acidity is possible;
• due to the presence of vitamin B12 in the formulation: erythremia, erythrocytosis, thromboembolism;
• due to the presence of lidocaine in the formulation: increased individual sensitivity to lidocaine or to other amide-type local anesthetics, history of lidocaine-induced epileptiform seizures, severe bradycardia, severe arterial hypotension, cardiogenic shock, severe forms of chronic heart failure (Grade II–III), sinus node dysfunction, Wolff–Parkinson–White syndrome, Adams–Stokes syndrome, second- and third-degree atrioventricular block, hypovolemia, severe hepatic/renal dysfunction, porphyria, myasthenia gravis.

Interaction with other medicinal products and other forms of interactions.

Vitamin B1 is completely degraded by sulfite-containing solutions. Other vitamins may be inactivated in the presence of vitamin B1 degradation products. Therapeutic doses of vitamin B6 may reduce the effect of L-dopa. Interactions are also possible with isoniazid, D-penicillamine, and cycloserine.

When lidocaine is administered parenterally, cardiac adverse effects may be enhanced when used concomitantly with adrenaline or noradrenaline. Interactions with sulfonamides are also possible.

In case of overdose of local anesthetics, adrenaline and noradrenaline must not be used.

Special precautions for use.

The medicinal product contains lidocaine hydrochloride and therefore should be administered only intramuscularly. Intravenous administration into the bloodstream is not permitted. In case of accidental intravenous injection, depending on the severity of the symptoms developed, medical supervision or hospital observation is required.

Prolonged use of the medicinal product for more than 6 months may lead to reversible peripheral sensory neuropathy.

The medicinal product contains benzyl alcohol.

Benzyl alcohol has been associated with the risk of serious adverse effects ("gasping syndrome") in newborns and young children.

Due to the risk of accumulation and toxicity (metabolic acidosis), large amounts of benzyl alcohol should be used cautiously and only when absolutely necessary, especially in patients with impaired liver or kidney function, as well as during pregnancy and breastfeeding.

The medicinal product contains less than 1 mmol/dose of sodium, i.e. it is practically sodium-free.

Use during pregnancy or breastfeeding.

During pregnancy, the recommended daily intake of vitamin B1 is 1.2 mg in the 2nd trimester and 1.3 mg in the 3rd trimester, and vitamin B6 — 1.9 mg from the 4th month of pregnancy. The medicinal product should be used during pregnancy only if vitamin B1 and B6 deficiency has been confirmed in the patient, as the safety of doses exceeding the recommended daily intake has not been established.

During breastfeeding, the recommended daily intake of vitamin B1 is 1.3 mg and vitamin B6 is 1.9 mg.

Vitamins B1, B6, and B12 pass into breast milk. High doses of vitamin B6 may reduce milk production.

The medicinal product contains 100 mg of vitamin B6 per 1 ampoule; therefore, it should not be used during pregnancy or breastfeeding.

The decision on using the medicinal product during pregnancy and breastfeeding should be made by a physician only after evaluating the risk/benefit ratio.

Ability to affect reaction speed when driving vehicles or operating machinery.

The medicinal product does not affect the ability to drive vehicles or operate machinery.

Method of Administration and Dosage.

Method of Administration.

The medicinal product is intended for intramuscular injection.

Intravenous administration into the bloodstream is not permitted. In case of accidental intravenous injection, depending on the severity of symptoms, medical monitoring or hospital observation is required.

Injections should be administered deep into the muscle (intramuscularly).

Dosage.

In cases of severe and acute pain, administer the medicinal product at a dose of 2 ml once daily until acute symptoms subside. After completion of the acute phase and in mild disease conditions, administer the medicinal product at a dose of 2 ml 2–3 times per week.

Weekly medical monitoring is recommended during therapy.

Early transition to oral therapy should be pursued whenever possible.

Children.

The medicinal product must not be used in children.

Overdose.

Vitamin B1 has a wide therapeutic range. Very high doses (more than 10 g) may produce curare-like effects, suppressing nerve impulse conduction.

Vitamin B6 has very low toxicity. Excessive use of vitamin B6 in doses exceeding 1 g per day over several months may lead to neurotoxic effects. Neuropathies with ataxia and sensory disturbances, cerebral convulsions with ECG changes, and in isolated cases hypochromic anemia and seborrheic dermatitis have been reported after administration of more than 2 g per day.

Vitamin B12: following parenteral administration (rarely, after oral use) of doses higher than recommended, allergic reactions, eczematous skin disorders, and benign forms of acne have been observed. With prolonged use at high doses, possible disturbances in liver enzyme activity, chest pain, and hypercoagulation may occur.

Treatment: symptomatic therapy.

Lidocaine: symptoms of overdose include psychomotor agitation, dizziness, general weakness, decreased arterial pressure, tremor, visual disturbances, tonic-clonic seizures, coma, collapse, possible atrioventricular block, central nervous system depression, and respiratory arrest. Initial symptoms of overdose in healthy individuals occur at blood lidocaine concentrations exceeding 0.006 mg/kg; seizures occur at 0.01 mg/kg.

Treatment: discontinue administration of the medicinal product, administer oxygen therapy, anticonvulsants, vasoconstrictors (noradrenaline, mesaton), and in case of bradycardia—anticholinergics (0.5–1 mg atropine). Intubation, artificial ventilation of the lungs, and resuscitation measures may be necessary. Dialysis is ineffective.

Side effects.

Side effects are classified by organ system and frequency of occurrence: 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 (frequency cannot be determined from available data).

Immune system disorders:

very rare — hypersensitivity reactions (e.g., exanthema, dyspnea, shock, angioedema); not known — allergic reactions caused by benzyl alcohol.

Cardiovascular system disorders:

very rare — tachycardia.

Skin and subcutaneous tissue disorders:

very rare — sweating, acne, pruritic skin reactions including urticaria.

General disorders and administration site conditions:

not known — burning sensation at injection site; systemic reactions may occur due to rapid accumulation (e.g., accidental intravenous injection, injection into highly vascularized tissue) or overdose, including dizziness, vomiting, bradycardia, cardiac arrhythmias, and seizures.

Reporting suspected adverse reactions.

Reporting suspected adverse reactions after marketing authorization of the medicinal product is highly important. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare 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.

3 years.

Storage conditions.

Store at 2–8 °C in the original packaging and in a place inaccessible to children.

Incompatibilities.

Vitamin B1 is incompatible with oxidizing and reducing agents: mercury chloride, iodides, carbonates, acetates, tannic acid, iron-ammonium citrate, as well as with sodium phenobarbital, riboflavin, benzylpenicillin, glucose, and metabisulfite, as it becomes inactivated in their presence. Copper accelerates thiamine degradation; in addition, thiamine loses its activity at increased pH values (above 3).

Vitamin B12 is incompatible with oxidizing and reducing agents and with heavy metal salts.

In solutions containing thiamine, vitamin B12, like other components of the B-complex group, is rapidly degraded by thiamine breakdown products (low concentrations of iron ions may protect against this). Riboflavin, particularly under light exposure, also causes degradation; nicotinamide accelerates photolysis, whereas antioxidants exert an inhibitory effect.

Packaging.

2 ml in ampoules; 5 ampoules in a blister pack; 1 blister pack in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

WORLD MEDICINE ILAC SAN. VE TIC. A.S., Turkey.

Manufacturer's address.

COSB G.O.Pasa Mah. 6. Cad. No:30, Cerkezkoy/Tekirdag, Turkey.

Marketing Authorization Holder.

WORLD MEDICINE, LLC, Ukraine.