Neuraxin® b
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NEIRAXIN® B (NEIRAXIN® B)
Composition:
Active substances: pyridoxine, thiamine, cyanocobalamin, lidocaine;
Each 2 ml solution (1 ampoule) contains: pyridoxine hydrochloride (vitamin B6) — 100 mg, thiamine hydrochloride (vitamin B1) — 100 mg, cyanocobalamin (vitamin B12) — 1 mg, lidocaine hydrochloride — 20 mg;
Excipients: benzyl alcohol, sodium tripolyphosphate, sodium hydroxide, potassium hexacyanoferrate (III), water for injections.
Pharmaceutical form. Solution for injection.
Main physicochemical properties: clear red-colored solution.
Pharmacotherapeutic group. Vitamin B1 in combination with vitamin B6 and/or vitamin B12. ATC code A11D B.
Pharmacological Properties
Pharmacodynamics
Neurotropic B-group vitamins exert beneficial effects on inflammatory and degenerative diseases of the nerves and musculoskeletal system. They are used to correct deficiency states, and at high doses possess analgesic properties, improve blood circulation, and help normalize the function of the nervous system and hematopoiesis.
Vitamin B1 is a highly important active substance. In the body, vitamin B1 is phosphorylated to form biologically active thiamine diphosphate (co-carboxylase) and thiamine triphosphate (TTP).
Thiamine diphosphate acts as a coenzyme in essential 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 and pyruvic acids—leading to various pathological conditions and disturbances in nervous system function.
In its phosphorylated form (pyridoxal-5’-phosphate, PALP), vitamin B6 acts as a coenzyme for several enzymes involved in general non-oxidative amino acid metabolism. Through decarboxylation, these enzymes participate in the formation of physiologically active amines (epinephrine, histamine, serotonin, dopamine, tyramine); through transamination, they contribute to anabolic and catabolic metabolic processes (e.g., glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, γ-aminobutyric acid, α-ketoglutarate transaminase), as well as various amino acid breakdown and synthesis processes. Vitamin B6 affects four different stages in tryptophan metabolism. In hemoglobin synthesis, vitamin B6 catalyzes the formation of α-amino-β-keto-adipic acid.
Vitamin B12 is essential for cellular metabolism. It influences hematopoietic function (as an extrinsic anti-anemic factor), participates in the formation of choline, methionine, creatinine, and nucleic acids, and has analgesic effects.
Pharmacokinetics
After parenteral administration, thiamine is distributed throughout the body. Approximately 1 mg of thiamine is degraded daily. Metabolites are excreted in urine.
Dephosphorylation 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. Pyridoxal is the transport form. To cross 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 organs. 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 medicinal product; acute impairment of cardiac conduction; acute phase of decompensated heart failure.
Vitamin B1 — contraindicated in allergic reactions.
Vitamin B6 — contraindicated in peptic ulcer of the stomach and duodenum in the acute phase (due to possible increase in gastric juice acidity).
Vitamin B12 — contraindicated in erythremia, erythrocytosis, thromboembolism.
- Lidocaine * — contraindicated in patients with increased individual sensitivity 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 (grades II–III), sick sinus syndrome, Wolff–Parkinson–White syndrome, Adams–Stokes syndrome, second- and third-degree atrioventricular block, hypovolemia, severe hepatic/renal dysfunction, porphyria, myasthenia gravis.
Pregnancy and breastfeeding period.
Interaction with other medicinal products and other forms of interaction
Thiamine is completely degraded by sulfite-containing solutions. Other vitamins may be inactivated by degradation products of vitamin B1. Therapeutic doses of vitamin B6 may reduce the effect of L-dopa. Interaction also occurs with isoniazid, D-penicillamine, and cycloserine.
When lidocaine is administered parenterally, cardiac adverse effects may be enhanced by concomitant use of adrenaline or noradrenaline. Interaction also occurs with sulfonamides.
Adrenaline and noradrenaline must not be used in cases of overdose of local anesthetics.
Special precautions for use
Neuraxin® B contains lidocaine hydrochloride and therefore must be administered only intramuscularly. Intravenous (i.v.) administration into the bloodstream is not permitted. In case of accidental intravenous injection, depending on the severity of symptoms, medical monitoring or hospital observation may be required. Prolonged use of the medicinal product for more than 6 months may lead to reversible peripheral sensory neuropathy.
Neuraxin® B contains benzyl alcohol. Benzyl alcohol has been associated with the risk of serious adverse effects ("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.
The medicinal product contains less than 1 mmol of sodium (23 mg) per dose unit and is therefore 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 is 1.9 mg from the 4th month of pregnancy. The medicinal product may be used during pregnancy only if a deficiency in vitamins B1 and B6 has been confirmed, as the safety of doses exceeding the recommended daily intake has not been established.
Breastfeeding period. The recommended daily intake of vitamin B1 for breastfeeding mothers 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.
Neuraxin® B contains 100 mg of vitamin B6 per ampoule; therefore, it should not be used during pregnancy or breastfeeding.
The decision to use this medicinal product during pregnancy or breastfeeding should be made only after careful assessment by a physician of the potential risks and benefits.
Ability to affect reaction speed when driving or operating machinery. Neuraxin® B does not affect the ability to drive vehicles 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, administer one injection (2 ml) once daily initially. After the acute phase has resolved and in mild conditions, 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
Administer intramuscularly. The injection should be given deeply into the muscle.
Warning Against Accidental Intravenous Injection
Neuraxin® must be administered only by intramuscular (i.m.) route. 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.
How to Open the Ampoule
- Turn the ampoule with the colored dot facing toward you. Gently tap the top of the ampoule with your finger to allow the solution to flow down to the lower part.
- Use both hands to open the ampoule: hold the lower part of the ampoule in one hand and press the top part away from the colored dot with the other hand (see illustration below).
Children. Not intended for use in pediatric patients.
Overdose
Vitamin B1 has a wide therapeutic range. Very high doses (more than 10 g) may produce curare-like effects, inhibiting 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 changes on electroencephalogram (EEG), 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), doses higher than recommended have been associated with allergic reactions, eczematous skin disorders, and benign forms of acne.
Prolonged use in high doses may lead to impaired liver enzyme activity, chest pain, and hypercoagulability.
Treatment: symptomatic therapy.
Symptoms of lidocaine overdose: psychomotor agitation, dizziness, general weakness, decreased arterial blood pressure, tremor, visual disturbances, tonic-clonic seizures, coma, collapse, possible atrioventricular block, central nervous system 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, anticonvulsant agents, vasoconstrictors (norepinephrine, mesaton), in case of 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
The frequency of adverse reactions is defined according to 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: cannot be estimated from the available data.
Immune system disorders:
Very rare: hypersensitivity reactions (e.g., exanthema, dyspnea, shock, angioneurotic edema).
Not known: benzyl alcohol may cause allergic reactions.
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 may occur due to rapid accumulation (accidental intravenous injection, injection into highly vascularized tissue) 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 highly important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and pharmacists, 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. 2 years.
Do not use after the expiry date stated on the packaging.
Storage conditions
Store in a refrigerator at a temperature of 2 °C to 8 °C. Do not freeze.
Keep in the original packaging to protect from light.
Keep out of the reach of children.
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; 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, as well as other components of the B-complex vitamins, is rapidly degraded by thiamine breakdown products (low concentrations of iron ions may offer protection against this). Riboflavin, particularly under exposure to light, also causes degradation; nicotinamide accelerates photolysis, whereas antioxidants exert an inhibitory effect.
Packaging
2 ml in a vial made of brown, light-protective, hydrolytic glass of Class I, with scoring rings and a break point or score line.
5 vials in a blister pack (cavity) made of non-coated polyvinyl chloride film.
1, 2, or 5 blister packs (cavities) in a cardboard box.
Prescription status. Prescription only.
Manufacturer
Manufacturer responsible for batch release: JSC "Kalceks".
Manufacturer's address and place of business
71E Krustpils Street, Riga, LV-1057, Latvia.
Marketing Authorization Holder. JSC "Kalceks".
Address of the Marketing Authorization Holder. 71E Krustpils Street, Riga, LV-1057, Latvia.