Neuromax

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

Composition:

Active substances: 1 ml of solution contains pyridoxine hydrochloride 50 mg, thiamine hydrochloride 50 mg, cyanocobalamin 0.5 mg;

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

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear 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 group B exert beneficial effects in inflammatory and degenerative diseases of nerves and the musculoskeletal system. They are used to correct deficiency states, and in high doses possess analgesic properties, improve blood circulation, and normalize nervous system function and hematopoiesis.

Vitamin B1 (thiamine) is a highly important active substance. In the body, vitamin B1 is phosphorylated to form biologically active thiamine diphosphate (cocarboxylase) and thiamine triphosphate (TTP).

Thiamine diphosphate acts as a coenzyme in key carbohydrate metabolism processes, which are crucial for metabolic functions of nervous tissue and influence nerve impulse transmission in synapses. In vitamin B1 deficiency, metabolites accumulate in tissues, primarily lactic and pyruvic acids, leading to various pathological conditions and disorders of nervous system function.

Vitamin B6 (pyridoxine), in its phosphorylated form (pyridoxal-5’-phosphate, PALP), serves as a coenzyme for a number of enzymes involved in general non-oxidative amino acid metabolism. Through decarboxylation, these enzymes participate in the formation of physiologically active amines (adrenaline, histamine, serotonin, dopamine, tyramine); through transamination – 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 processes of amino acid breakdown and synthesis. Vitamin B6 acts at four different sites in the metabolism of tryptophan. In hemoglobin synthesis, vitamin B6 catalyzes the formation of α-amino-β-keto-adipic acid.

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

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 0.35 hours. 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 are bound to albumin. The transport form is pyridoxal. For passage through the cell membrane, pyridoxal-5-phosphate bound to albumin is hydrolyzed by alkaline phosphatase to 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 enters bile and participates in enterohepatic circulation. Vitamin B12 crosses the placenta.

Clinical characteristics.

Indications.

Neurological disorders of various origins: neuritis, neuralgias, polyneuropathies (diabetic, alcoholic), radicular syndrome, retrobulbar neuritis, facial nerve lesions.

Contraindications.

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

Vitamin B1 is contraindicated in allergic reactions.

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

Vitamin B12 is contraindicated in erythremia, erythrocytosis, and thromboembolism.

Lidocaine. Hypersensitivity to lidocaine or 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 (II–III degree), sinus node dysfunction syndrome, Wolff-Parkinson-White syndrome, Adams-Stokes syndrome, second- and third-degree atrioventricular (AV) block, hypovolemia, severe hepatic/renal dysfunction, porphyria, myasthenia gravis.

Pregnancy and lactation period.

Interaction with other medicinal products and other types of interactions.

The action of thiamine is inactivated by 5-fluorouracil, as the latter competitively inhibits phosphorylation of thiamine to thiamine pyrophosphate. Loop diuretics, such as furosemide, which inhibit tubular reabsorption, may increase thiamine excretion and thus reduce thiamine levels during long-term therapy.

Concomitant use with levodopa is contraindicated, as vitamin B6 may reduce the antiparkinsonian effect of levodopa. Concurrent use with pyridoxine antagonists (e.g., isoniazid, hydralazine, penicillamine, or cycloserine) and oral contraceptives may increase the requirement for vitamin B6.

Consumption of beverages containing sulfites (e.g., wine) increases thiamine degradation.

Lidocaine potentiates the respiratory center depressant effects of anesthetic agents (hexobarbital, intravenous thiopental sodium), hypnotics, and sedatives; reduces the cardiotonic effect of digoxin. Concomitant use with hypnotics and sedatives may enhance the central nervous system (CNS) depressant effects.

Ethanol enhances the respiratory depressant effect of lidocaine.

Beta-blockers (including propranolol, nadolol) when used concomitantly slow down hepatic metabolism of lidocaine, enhance lidocaine effects (including toxic effects), and increase the risk of bradycardia and hypotension. When beta-blockers and lidocaine are used together, the dose of lidocaine should be reduced.

Curare-like agents – possible deepening of myorelaxation (up to paralysis of respiratory muscles).

Norepinephrine, mexiletine – increased toxicity of lidocaine (reduced lidocaine clearance).

Isadrine (isoprenaline) and glucagon – increased lidocaine clearance.

Cimetidine, midazolam – increased plasma concentration of lidocaine. Cimetidine displaces lidocaine from plasma protein binding and slows hepatic inactivation of lidocaine, leading to an increased risk of enhanced adverse effects of lidocaine. Midazolam moderately increases lidocaine blood concentration.

Anticonvulsants, barbiturates (including phenobarbital, phenytoin) – when used concomitantly with lidocaine, may accelerate hepatic metabolism of lidocaine, reduce blood concentration, and enhance cardiodepressive effects.

Antiarrhythmic agents (amiodarone, verapamil, quinidine, ajmaline, disopyramide), anticonvulsants (hydantoin derivatives) – enhanced cardiodepressant effect; concomitant use with amiodarone may lead to seizures.

Procaine, procainamide – when used concomitantly with lidocaine, may cause CNS excitation and hallucinations.

Monoamine oxidase inhibitors, aminazine (chlorpromazine), bupivacaine, amitriptyline, nortriptyline, imipramine – when used concomitantly with lidocaine, increase the risk of arterial hypotension and prolong the local anesthetic effect of lidocaine.

Narcotic analgesics (morphine) – when used concomitantly with lidocaine, enhance the analgesic effect of narcotic analgesics, but also enhance respiratory depression.

Prenylamine – increased risk of ventricular arrhythmia of the "torsades de pointes" type.

Propafenone – possible increase in duration and severity of CNS-related adverse effects.

Rifampicin – possible reduction in lidocaine blood concentration.

Polymyxin B – respiratory function should be monitored.

Cardiac glycosides – when used concomitantly with lidocaine, the cardiotonic effect of cardiac glycosides is reduced.

Digitalis glycosides – in the setting of lidocaine intoxication, lidocaine may exacerbate the severity of AV block.

Vasoconstrictors (epinephrine, methoxamine, phenylephrine) – when used concomitantly with lidocaine, slow lidocaine absorption and prolong its effect.

Guanadrel, guanethidine, mecamylamine, trimethaphan – when used concomitantly for spinal and epidural anesthesia, increase the risk of pronounced hypotension and bradycardia.

Acetazolamide, thiazide and loop diuretics – when used concomitantly with lidocaine, reduce lidocaine's effect due to induction of hypokalemia.

Anticoagulants (including ardeparin, dalteparin, danaparoid, enoxaparin, heparin, warfarin) – when used concomitantly with lidocaine, increase the risk of bleeding.

Agents causing neuromuscular blockade – when used concomitantly with lidocaine, enhance the effect of neuromuscular blocking agents, as lidocaine reduces nerve impulse conduction.

Special precautions for use

The medicinal product should not be administered intravenously.

Intramuscular injections of vitamin B12 may cause anaphylactic reactions in patients with increased sensitivity.

Parenteral administration of vitamin B12 may temporarily affect the diagnosis of funicular myelosis or pernicious anemia.

Prolonged use of vitamin B6 (more than 6–12 months) at doses exceeding 50 mg daily, or doses exceeding 1000 mg per day (for more than 2 months), may lead to reversible peripheral sensory neuropathy. If symptoms of peripheral sensory neuropathy (paresthesia) occur, the dose should be adjusted and, if necessary, treatment discontinued.

The preparation contains less than 1 mmol (23 mg)/dose of sodium, i.e. practically sodium-free.

The preparation contains less than 1 mmol (39 mg)/dose of potassium, i.e. practically potassium-free.

Since the preparation contains vitamin B6, it should be used with caution in patients with a history of peptic ulcer of the stomach and duodenum, or with pronounced impairment of renal and hepatic function.

Patients with neoplasms, except in cases associated with megaloblastic anemia and vitamin B12 deficiency, should not be treated with this preparation.

The preparation should not be used in severe forms of cardiac decompensation or angina pectoris.

Since the preparation contains lidocaine, it should be noted that the use of disinfectant solutions containing heavy metals for injection site preparation increases the risk of local reactions such as pain and swelling.

Since lidocaine exerts a pronounced antiarrhythmic effect and may itself act as an arrhythmogenic factor, the preparation should be used with caution in individuals with a history of arrhythmia.

Use with caution in patients with moderate heart failure, moderate arterial hypotension, incomplete AV block, intraventricular conduction disturbances, moderate impairment of liver and kidney function (creatinine clearance 10 ml/min), respiratory dysfunction, epilepsy, after cardiac surgery, in patients with genetic predisposition to hyperthermia, debilitated patients, and elderly patients.

ECG monitoring is mandatory during lidocaine administration. If sinus node dysfunction, PQ interval prolongation, QRS complex widening, or development of a new arrhythmia occurs, the dose should be reduced or the drug discontinued.

Before using lidocaine in cardiac disorders (hypokalemia reduces lidocaine efficacy), serum potassium levels must be normalized.

After intramuscular administration, creatinine concentration may increase, potentially leading to misdiagnosis of acute myocardial infarction.

Use during pregnancy or breastfeeding

During pregnancy and breastfeeding, the recommended daily intake of vitamin B1 is 1.4–1.6 mg and vitamin B6 is 2.4–2.6 mg. During pregnancy, these doses may be higher if the patient has a deficiency of B1 and B6.

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

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

Ability to affect reaction speed when driving or operating machinery

The medicinal product does not affect the ability to drive or operate machinery. However, if dizziness occurs during treatment, driving or operating machinery should be avoided.

Administration and Dosage.

For intramuscular use.

Skin tests with local anesthetics should be performed in individuals who have had confirmed reactions to these agents. Provocation tests are recommended if skin tests yield negative results. Testing of patients with proven allergic reactions to local anesthetics should be performed only by allergologists experienced in drug allergy.

In severe (acute) cases, treatment should be initiated with 2 mL of the solution administered intramuscularly once daily until acute symptoms subside. For continuation of treatment, administer 2 mL (1 injection) 2–3 times per week. The treatment course should last at least 1 month.

Intramuscular injections should be administered into the upper outer quadrant of the gluteal muscle.

For maintenance or continuation of the therapeutic course of injections, or for prevention of relapse, the medicinal product Neuramax, film-coated tablets, is recommended.

Children. The drug is not intended for use 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 EEG 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.

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

Treatment: symptomatic therapy.

Lidocaine. Symptoms: psychomotor agitation, dizziness, general weakness, decreased arterial pressure, tremor, visual disturbances, tonic-clonic seizures, coma, collapse, possible AV block, CNS depression, 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 drug administration, oxygen therapy, anticonvulsants, vasopressors (norepinephrine, mesaton), for bradycardia – anticholinergics (0.5–1 mg atropine). Endotracheal intubation, artificial ventilation of the lungs, and resuscitation measures may be necessary. Dialysis is ineffective.

Adverse Reactions.

Long-term use (over 6–12 months) at doses exceeding 50 mg of vitamin B6 daily may lead to peripheral sensory neuropathy, nervous excitement, malaise, dizziness, headache.

Gastrointestinal system: gastrointestinal disturbances, including nausea, vomiting, diarrhea, abdominal pain, increased gastric acidity.

Immune system: hypersensitivity reactions (skin rashes, respiratory disturbances, anaphylactic shock, angioedema), increased sweating.

Skin: pruritus, urticaria, acneiform eruptions, generalized exfoliative dermatitis.

Cardiovascular system: tachycardia, arrhythmias, bradycardia, slowed cardiac conduction, atrioventricular block, cardiac arrest, peripheral vasodilation, collapse, increased/decreased blood pressure, chest pain.

Nervous system: CNS excitation (when used in high doses), restlessness, headache, dizziness, sleep disturbances, confusion, drowsiness, loss of consciousness, coma; in patients with increased sensitivity – euphoria, tremor, trismus, motor restlessness, paresthesia, seizures.

Eye disorders: nystagmus, reversible blindness, diplopia, flickering "floaters" before the eyes, photophobia, conjunctivitis.

Ear and labyrinth disorders: hearing disturbances, tinnitus, hyperacusis.

Respiratory system: dyspnea, rhinitis, respiratory depression or respiratory arrest.

Other: sensations of heat, cold, or numbness in extremities, edema, weakness, malignant hyperthermia, sensory disturbances, motor block.

General disorders: injection site reactions.

With very rapid parenteral administration, systemic reactions such as seizures may occur.

Shelf life. 2 years.

Storage conditions. Store in original packaging at a temperature between 2 °C and 8 °C.

Keep out of reach of children.

Incompatibility.

Pyridoxine is incompatible with drugs containing levodopa, as concomitant use enhances peripheral decarboxylation of levodopa, thereby reducing its antiparkinsonian effect.

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; in addition, thiamine loses its activity when the pH of the preparation increases by more than 3 units (toward alkalinity) from the initial level.

Cyanocobalamin is incompatible with heavy metal salts.

Packaging. 2 ml in ampoules, packs of 5, 10 in a box; 5, 5×2, 10 in blister packs in a box.

Prescription status. Prescription only.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA".

Manufacturer's address and place of business.

22 Shevchenka Street, Kharkiv, Kharkiv Oblast, 61013, Ukraine.