Neurolek

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

Composition:

Active substances: thiamine hydrochloride, pyridoxine hydrochloride, cyanocobalamin;

1 ml of solution contains thiamine hydrochloride (calculated as 100% substance) 50 mg, pyridoxine hydrochloride (calculated as 100% substance) 50 mg, cyanocobalamin (calculated as 100% substance) 0.5 mg;

Excipients: lidocaine hydrochloride, benzyl alcohol, sodium polyphosphate, potassium ferrocyanide, sodium hydroxide, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear red-colored liquid.

Pharmacotherapeutic group. Vitamin B1 preparations in combination with vitamin B6 and/or vitamin B12. ATC code A11DB.

Pharmacological Properties

Pharmacodynamics

Neurotropic B-group vitamins exert beneficial effects on inflammatory and degenerative disorders of nerves and the musculoskeletal system. They are used to correct deficiency states, and in high doses possess analgesic properties, improve blood circulation, and help normalize nervous system function and hematopoiesis.

Vitamin B1 is a highly important active substance. In the body, vitamin B1 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 transmission in synapses. In vitamin B1 deficiency, metabolites accumulate in tissues—primarily lactic acid and pyruvic acid—leading to various pathological conditions and nervous system dysfunction.

Vitamin B6, in its phosphorylated form (pyridoxal-5’-phosphate, PALP), 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, vitamin B6 catalyzes the formation of δ-aminolevulinic acid.

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

Pharmacokinetics

After parenteral administration, thiamine 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 21 minutes. Thiamine does not accumulate in the body due to its limited lipid solubility.

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

After parenteral administration, vitamin B12 forms transport protein complexes that are rapidly absorbed by the liver, bone marrow, and other proliferative tissues. Vitamin B12 is excreted into bile and participates in enterohepatic circulation. Vitamin B12 crosses the placenta.

Clinical characteristics.

Indications.

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

Contraindications.

Hypersensitivity to the components of the drug; acute impairment of cardiac conduction; acute form of decompensated heart failure.

Vitamin B1 is contraindicated in allergic reactions.

Vitamin B6 is contraindicated in peptic ulcer of the stomach and duodenum in the acute phase (due to possible increase in gastric juice acidity).

Vitamin B12 is contraindicated in erythremia, erythrocytosis, thromboembolism.

Lidocaine. Hypersensitivity to lidocaine or to other amide-type local anesthetics, history of epileptiform seizures induced by lidocaine, severe bradycardia, severe arterial hypotension, cardiogenic shock, severe forms of chronic heart failure (Grade II–III), sick sinus syndrome, Wolff-Parkinson-White syndrome, Adams-Stokes syndrome, second- and third-degree atrioventricular (AV) block, hypovolemia, severe hepatic/renal dysfunction, porphyria, myasthenia gravis.

Do not use the drug during pregnancy and/or breastfeeding.

Interaction with other medicinal products and other forms of interaction.

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

When lidocaine is administered parenterally, cardiac adverse effects may be potentiated by concomitant use of adrenaline (epinephrine) or noradrenaline (norepinephrine). In addition, the drug interacts with sulfonamides.

Adrenaline and noradrenaline must not be used in cases of overdose with local anesthetics.

Special precautions for use

Neurolek contains lidocaine hydrochloride; therefore, the medicinal product should be administered only by intramuscular injection. Intravenous (i.v.) administration into the bloodstream is not permitted. In case of accidental intravenous injection, medical supervision or hospital observation is required depending on the severity of symptoms.

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

The medicinal product contains 23 mg of sodium per ampoule (2 mL) and is therefore practically sodium-free.

Neurolek contains benzyl alcohol.

Benzyl alcohol has been associated with a risk of serious adverse reactions ("gasping syndrome") in neonates and young children.

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

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 is 1.9 mg from the 4th month of pregnancy. The use of this medicinal product during pregnancy is possible only when a deficiency of vitamins B1 and B6 has been confirmed, 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 are excreted into breast milk. High doses of vitamin B6 may reduce milk production.

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

The decision regarding the use of this medicinal product during pregnancy or breastfeeding should be made by a physician only after careful assessment of the benefit-risk ratio.

Ability to affect reaction speed when driving or operating machinery

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

Method of Administration and Dosage

Dosage. In cases of severe and acute pain, to achieve a rapid increase in drug levels in the blood, initially administer one injection (2 ml) once daily. After the acute phase has subsided and in mild disease states, administer one injection 2–3 times per week.

Weekly medical monitoring is recommended during therapy.

It is advisable to switch to oral therapy as early as possible.

Method of Administration. Injections are administered deep intramuscularly (i.m.).

Warning against intravenous injection.

The medicinal product is intended for intramuscular (i.m.) use only. Intravenous (i.v.) administration into the circulatory system is not permitted. In case of accidental intravenous injection, medical monitoring or hospital observation is required depending on the severity of symptoms.

To maintain or continue the therapeutic course of injections or for prevention of relapse, oral medications of a similar pharmacotherapeutic group are recommended.

Children. The drug should 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 at doses exceeding 1 g per day over several months may lead to neurotoxic effects.

Neuropathies with ataxia and sensory disturbances, cerebral convulsions with EEG changes, as well as, 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 administration) of doses higher than recommended, allergic reactions, eczematous skin disorders, and benign forms of acne have been observed.

Prolonged use at high doses may lead to impaired liver enzyme activity, chest pain, and hypercoagulability.

Treatment: symptomatic therapy.

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

Treatment: discontinue drug administration, oxygen therapy, anticonvulsants, vasoconstrictors (norepinephrine, mesaton), 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.

The frequency of adverse reactions is defined using the following categories:

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 estimated from the available data.

Immune system disorders: not known – benzyl alcohol may cause allergic reactions; very rare – hypersensitivity reactions (e.g., exanthema, dyspnea, shock, angioedema).

Cardiovascular system disorders: very rare – tachycardia.

Skin and subcutaneous tissue disorders: very rare – sweating, acne, skin reactions with pruritus and urticaria.

General disorders and administration site conditions: not known – systemic reactions due to rapid accumulation (accidental intravenous injection, injection into tissue with high blood supply) or overdose. Dizziness, vomiting, bradycardia, cardiac arrhythmias, seizures. Burning sensation at the injection site.

Reporting of suspected adverse reactions. Reporting suspected adverse reactions after marketing authorization is of great importance. It allows ongoing 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 via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. Keep out of reach of children. Store in the original packaging at a temperature between 2 and 8 °C.

Incompatibilities.

Thiamine 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; additionally, 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 members of the B-complex group, is rapidly degraded by thiamine degradation products (low concentrations of iron ions may provide protection). Riboflavin, particularly under light exposure, also exerts a destructive effect; nicotinamide accelerates photolysis, whereas antioxidants have an inhibitory effect.

Packaging. 2 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 operations.

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