Instructions Neurobion solution for injection ampoule 3 ml No. 3
Composition
1 ampoule (3 ml) contains: thiamine hydrochloride (vitamin B1) 100 mg, pyridoxine hydrochloride (vitamin B6) 100 mg, cyanocobalamin (vitamin B12) 1 mg;
Excipients: sodium hydroxide solution 1M, potassium cyanide, water for injection.
Dosage form
Solution for injection.
Main physicochemical properties: red, clear solution.
Pharmacotherapeutic group
Vitamin B1 preparations in combination with vitamin B6 and/or vitamin B12. ATX code A11D B.
Pharmacological properties
Pharmacodynamics
The drug in the form of ampoules contains a combination of neurotropic active substances of the B vitamin complex. The vitamins included in the drug, namely: thiamine (B1), pyridoxine (B6) and cobalamin (B12), play a special role as coenzymes in the intermediate metabolism that occurs in the central and peripheral nervous system. Like all vitamins, they are essential nutrients that the body cannot synthesize on its own. Therapeutic use of vitamins B1, B6 and B12 compensates for their insufficient intake with food and thus ensures the presence of the necessary amount of coenzymes in the body.
Thiamine (vitamin B1). Thiamine pyrophosphate (TPP) is the active form of vitamin B1 and acts as a coenzyme for a number of enzymes (e.g. pyruvate dehydrogenase and transketolase). Accordingly, vitamin B1 is primarily involved in carbohydrate metabolism, but it is also involved in the synthesis of lipids and amino acids. Nerve cells cover their energy needs exclusively through the enzymatic oxidation and decarboxylation of glucose, so an adequate supply of vitamin B1 is very important. Thiamine is involved in the conduction of nerve impulses.
Pyridoxine (vitamin B6). Pyridoxal phosphate, the biologically active form of pyridoxine, is a key coenzyme in amino acid metabolism. It participates in the formation of physiologically active amines (e.g. serotonin, histamine, adrenaline) by decarboxylation processes, as well as in anabolic and catabolic processes by transamination. Pyridoxal phosphate plays an important role in the central nervous system, especially in enzymatically controlled neurotransmitter metabolism. As a catalyst for the first steps in the biosynthesis of sphingosine, pyridoxal phosphate also plays a key role in the metabolism of sphingolipids - important components of the myelin sheaths of nerve cells.
Cobalamin (vitamin B12). Vitamin B12 in its active form (5-deoxyadenosylcobalamin and methylcobalamin) is involved in enzyme-catalyzed intramolecular hydrogen transfer and intramolecular methyl group transfer. Vitamin B12 is also involved in the synthesis of methionine (closely related to nucleic acid synthesis) and in lipid metabolism by converting propionic acid to succinic acid. Vitamin B12 is involved in the methylation of the myelin core protein, which is a component of the myelin sheaths of the nervous system. Methylation increases the lipophilic properties of the core protein, improving incorporation into the myelin sheath.
Combination of vitamins B1, B6 and B12. Given their biochemical functions, vitamins B1, B6 and B12 are particularly important for the metabolic processes of the nervous system, both individually and in combination. In addition, most vulnerable groups of patients, such as elderly patients, diabetics and others, have a deficiency of all three of these neurotropic vitamins. Animal studies have shown that this combination of neurotropic B vitamins accelerates regenerative processes in damaged nerve fibers, which in turn leads to a faster restoration of muscle function and innervation. The use of combinations of B vitamins in diabetic rats prevented nerve damage or attenuated the damage in such a way that the deterioration of functional properties was reduced (anti-neuropathic effect).
In animal experiments and in clinical studies, the antinociceptive effect of vitamins B1, B6, and B12 has been shown.
Pharmacokinetics
The combined use of vitamins B1, B6 and B12 does not in any way affect the pharmacokinetics of the individual vitamins.
Thiamine (vitamin B1)
The biological half-life in humans is approximately 9.5–18.5 days with a half-life of approximately 4 hours. The human body can store 20–30 mg of thiamine (mainly in the heart, brain, liver and kidneys). Due to rapid metabolism, reserves are very limited and are used up after 4–10 days.
Pyridoxine (vitamin B6)
Vitamin B6 is primarily phosphorylated in the liver to form the biologically active form pyridoxal phosphate. To cross the cell membrane, phosphorylated vitamin B6 must be hydrolyzed by alkaline phosphatase to release vitamin B6. Transport within the cell occurs by diffusion followed by rephosphorylation. The biological half-life of pyridoxal phosphate is 15–25 days, and the elimination half-life is approximately 3 hours. Approximately 40–150 mg can be stored in the human body, with accumulation occurring over 14–42 days, and urinary excretion is 1.7–3.6 mg per day.
Oral vitamin B12 has a low absorption rate, which may be further reduced after bariatric surgery, in elderly patients, in patients on dialysis, and in patients with other forms of malabsorption. In addition to the saturable active absorption of orally administered vitamin B12 with a maximum daily absorption rate of approximately 1.5 μg, vitamin B12 can also be absorbed by passive diffusion. The fraction absorbed by passive diffusion is only approximately 1–2% of the ingested amount. It may be further reduced in patients who have undergone bariatric surgery or who have impaired gastrointestinal absorption due to other diseases. Parenteral administration may be appropriate for such patients.
Approximately 90% of cobalamin in blood plasma is bound to proteins (transcobalamins). Vitamin B12 does not circulate in blood plasma, accumulating mainly in the liver, its daily requirement is approximately 1 μg. The metabolic rate is 2.5 μg/day, or 0.05% of the stored amount.
Vitamin B12 is secreted mainly into the bile and is reabsorbed in large quantities through the enterohepatic circulation. If the body's storage capacity is exceeded due to the administration of high doses, especially parenterally, the excess is excreted in the urine.
Indication
Neurological diseases accompanied by severe deficiency of vitamins B1, B6 and B12, which cannot be eliminated with oral agents.
Contraindication
Hypersensitivity to the active substances or to any of the excipients.
Vitamin B1 is contraindicated in allergic diseases.
Vitamin B6 is contraindicated in gastric and duodenal ulcers in the acute stage (since it may increase the acidity of gastric juice).
Vitamin B12 is contraindicated in erythremia, erythrocytosis, and thromboembolism.
It is contraindicated for use in children (under 18 years of age).
Special safety precautions
Use syringes and needles (not included in the Neurobion package) only once. Syringes and needles should be disposed of immediately after use. Any unused medicinal product or waste material should be disposed of in accordance with applicable legislation.
It is not recommended to mix Neurobion, solution for injection, with other medicines in the same syringe.
Interaction with other medicinal products and other types of interactions
5-Fluorouracil. Thiamine is inactivated by 5-fluorouracil, as the latter competitively inhibits the phosphorylation of thiamine to thiamine pyrophosphate.
Loop diuretics: Loop diuretics, such as furosemide, may increase thiamine excretion with long-term use by inhibiting tubular reabsorption and thus reduce serum levels of vitamin B1 (thiamine).
Levodopa. When used simultaneously with levodopa, vitamin B6 may reduce the effect of levodopa.
Pyridoxine antagonists: Concomitant use of pyridoxine antagonists (e.g. isoniazid, hydralazine, D-penicillamine or cycloserine) may reduce the effectiveness of vitamin B6 (pyridoxine).
Application features
The drug cannot be administered intravenously.
Since Neurobion contains vitamin B6, the drug should be used with caution in patients with a history of peptic ulcer of the stomach and duodenum, severe renal and hepatic dysfunction.
Patients with neoplasms, except in cases accompanied by megaloblastic anemia and vitamin B12 deficiency, should not use the drug.
The drug should not be used in severe or acute forms of cardiac decompensation and angina pectoris.
Continuous monitoring for signs of peripheral sensory neuropathy is recommended during long-term use.
Short-term parenteral use of vitamin B12 may temporarily complicate the diagnosis of funicular myelosis or pernicious anemia.
If signs of peripheral sensory neuropathy (paresthesia) occur, the dosage of the drug should be reviewed and, if necessary, its use should be discontinued. Cases of neuropathy have been observed with long-term (over 6-12 months) use of vitamin B6 in daily doses of more than 50 mg, as well as with short-term (over 2 months) use of vitamin B6 in doses of more than 1 g per day.
Children
Experience with the use of the drug in children and adolescents is limited. Therefore, the drug is not recommended for use in this group of patients.
This medicine contains less than 1 mmol sodium (23 mg) per ampoule, i.e. essentially ‘sodium-free’.
This medicine contains less than 1 mmol (39 mg) of potassium per ampoule, i.e. essentially potassium-free.
Ability to influence reaction speed when driving vehicles or other mechanisms
If dizziness occurs during treatment with the drug, you should refrain from driving vehicles and operating machinery. This medicinal product has no or negligible influence on the ability to drive vehicles and operate machinery.
Use during pregnancy or breastfeeding
Animal studies on the effects of the drug on pregnancy, embryofetal, prenatal and postnatal development are insufficient. The potential risk to humans is unknown, therefore the drug is not recommended for use during pregnancy.
Breast-feeding
Vitamins B1, B6 and B12 are excreted in human breast milk. High concentrations of vitamin B6 (600 mg per day) may inhibit the production of breast milk. Animal studies on the extent of secretion into breast milk are not available. Therefore, the drug is not recommended for use during breastfeeding. A decision on whether to discontinue breastfeeding or to discontinue the drug should be made taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.
Method of administration and doses
The drug is intended for intramuscular administration.
Dosage
In severe (acute) cases: one ampoule per day until the intensity of acute symptoms decreases.
After symptoms subside: one ampoule 1-3 times a week.
To maintain or extend the initial therapeutic course of injections and to prevent relapse, it is recommended to use the drug in the form of film-coated tablets.
Children
Experience with the use of the drug in children and adolescents is limited. Therefore, the drug is not recommended for use in this group of patients.
Method of application
The drug should be administered intramuscularly (deep injection into the gluteal muscle).
Children
Do not use in children and adolescents (under 18 years of age).
Overdose
With prolonged use in high doses, liver enzyme activity disorders, pain in the heart area, and hypercoagulation are possible.
Vitamin B1
Thiamine has a wide therapeutic range. Very high doses (over 10 g) have a ganglion-blocking effect and inhibit nerve impulse conduction in a curare-like manner.
Vitamin B6
The toxicity of vitamin B6 can be considered very low.
However, long-term (> 6-12 months) use of vitamin B6 in daily doses exceeding 50 mg may cause peripheral sensory neuropathy. Symptoms gradually disappear after discontinuation of the drug.
Continuous use of vitamin B6 in daily doses exceeding 1 g for more than two months may lead to neurotoxic adverse reactions.
When using more than 2 g per day, cases of neuropathy with ataxia and sensory disturbances, cerebral seizures with changes on the EEG and, in isolated cases, hypochromic anemia and seborrheic dermatitis have been described.
In animal studies, high doses of vitamin B6 disrupted spermatogenesis.
Vitamin B12
After parenteral administration in large doses, eczematous skin lesions and acne-like rashes have been observed.
Adverse reactions
Adverse reactions are listed below, classified by system organ class and frequency. The assessment of adverse reactions is based on the following frequency classification:
very common (≥ 1/10); common (≥ 1/100, <1/10); uncommon (≥ 1/1000, <1/100); rare (≥ 1/10000, <1/1000); very rare (<1/10000); frequency unknown (cannot be estimated from the available data).
On the part of the immune system: rash, skin hyperemia.
Very rare: hypersensitivity reactions, e.g. sweating, tachycardia and skin reactions, in particular acne, eczema, itching and urticaria, as well as anaphylaxis.
From the nervous system: nervous excitement, malaise, dizziness, headache.
Frequency unknown: Long-term use (more than 6-12 months) of vitamin B6 in doses greater than 50 mg per day may lead to peripheral sensory neuropathy. Symptoms gradually decrease after discontinuation of the vitamin.
On the part of the digestive system: increased acidity of gastric juice.
Frequency unknown: gastrointestinal complaints such as nausea, vomiting, diarrhea, abdominal pain.
Skin and subcutaneous tissue disorders: Frequency unknown: eczematous skin lesions, acne and acne-like rashes have been observed after the use of high doses of vitamin B12.
Renal and urinary disorders: Frequency unknown: chromaturia (red discoloration of urine observed during the first hours after drug administration; normalization usually occurs shortly after drug withdrawal).
Systemic disorders and injection site complications
Frequency unknown: injection site reactions.
Expiration date
3 years.
Storage conditions
Store at 2-8°C, protected from light. Keep out of reach of children.
Incompatibility. It is not recommended to mix Neurobion, solution for injection, with other drugs in the same syringe.
Vitamin B1 is completely destroyed by sulfite-containing solutions.
Other vitamins, especially cyanocobalamin (vitamin B12), can be deactivated in the presence of drugs that act destructively on vitamin B1.
Packaging
3 ml in an ampoule; 3 ampoules in a cardboard box.
Vacation category
According to the recipe.
Producer
Merck Healthcare KGaA, Germany.
Location of the manufacturer and its business address
Frankfurter Strasse 250, Darmstadt, Hesse, 64293, Germany.
