Instructions Neurobion film-coated tablets blister pack No. 20
Composition
active ingredients:
1 film-coated tablet contains: thiamine disulfide (vitamin B1) 100 mg, pyridoxine hydrochloride (vitamin B6) 200 mg, cyanocobalamin (vitamin B12) 200 mcg;
excipients: magnesium stearate, methylcellulose, sodium starch glycolate (type A), gelatin, mannitol, talc, glycerin (85%), colloidal anhydrous silicon dioxide, purified water;
shell: mountain wax, gelatin, methylcellulose, acacia, glycerin (85%), povidone 25, calcium carbonate, colloidal anhydrous silicon dioxide, kaolin, titanium dioxide (E 171), talc, sucrose.
Dosage form
Film-coated tablets.
Main physicochemical properties: round, biconvex, shiny, almost white tablets, coated.
Pharmacotherapeutic group
Vitamin B1 preparations in combination with vitamin B6 and/or vitamin B12. ATX code A11D B.
Pharmacological properties
Pharmacodynamics
Thiamine (vitamin B1)
Thiamine pyrophosphate is the active form of vitamin B1, which acts as a coenzyme for a number of enzymes (such as pyruvate dehydrogenase and transketolase). As a result, vitamin B1 is mainly involved in carbohydrate metabolism, and also plays a role in the synthesis of lipids and amino acids. Nerve cells obtain energy exclusively through the enzymatic oxidation and decarboxylation of glucose, so it is important to ensure that a sufficient amount of vitamin B1 is supplied. Thiamine is also 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 (such as serotonin, histamine, adrenaline) by decarboxylation, as well as in anabolic and catabolic processes by transamination.
Pyridoxal phosphate plays an essential role in the functioning of the central nervous system, especially in the enzyme-controlled metabolism of neurotransmitters. Pyridoxal phosphate plays a key role in the metabolism of sphingolipids, as it catalyzes the first step in the biosynthesis of sphingosine. Sphingolipids are integral components of the myelin sheath 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 also affects methionine synthesis (closely related to nucleic acid synthesis) and lipid metabolism through the conversion of propionic acid to succinic acid.
Vitamin B12 is involved in the methylation of myelin basic protein, a component of the myelin sheath of nerve cells. Methylation increases the lipophilic properties of myelin basic 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. Most vulnerable groups of patients, such as the elderly, patients with diabetes, etc., are deficient in all 3 vitamins.
Animal studies show that a combination of B vitamins accelerates the regeneration of damaged pathways in the nervous system, leading to faster recovery of function and muscle innervation.
The use of combinations of B vitamins in diabetic rats prevented or reduced the characteristic nerve damage, thus counteracting the deterioration of functional properties (anti-neuropathic effect). The use of vitamins B1, B6 and B12 in a number of pain models in rats showed antinociceptive activity, with the predominant efficacy of such a combination over the administration of individual components.
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 transport mechanism after oral administration is dose-dependent and has a dual nature: active absorption - up to a concentration of 2 μmol and passive diffusion at concentrations exceeding 2 μmol.
Studies using radiolabeled thiamine have shown that duodenal absorption is highest, while absorption in the upper and middle small intestine is somewhat lower. Absorption in the stomach and distal small intestine is almost nonexistent. Thiamine formed in the colon is not absorbed.
After absorption by the intestinal mucosa, thiamine is transported to the liver via the hepatic portal system. In the liver, thiamine is phosphorylated by thiamine kinase to thiamine pyrophosphate (TPP) and thiamine triphosphate (TTP).
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 within 4–10 days. The main excretion products are: thiamine carboxylic acid, pyramine, thiamine and a number of metabolites that have not yet been identified (renal excretion). The more thiamine is taken, the more thiamine will be excreted unchanged in the urine within 4–6 hours.
Pyridoxine (vitamin B6)
Vitamin B6 (pyridoxine, pyridoxal and pyridoxamine) is rapidly absorbed, mainly in the upper gastrointestinal tract, and transported to organs and tissues. The vitamins bind to albumin. Approximately 80% of pyridoxal phosphate is bound to proteins. Vitamin B6 penetrates the cerebrospinal fluid, is secreted into breast milk and crosses the placental barrier. The main excretion product is 4-pyridoxic acid in an amount that depends on the dose of vitamin B6 used.
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. 40–150 mg can be accumulated, with accumulation occurring over 14–42 days.
Cyanocobalamin (vitamin B12)
Absorption from the gastrointestinal tract is based on 2 different mechanisms. The active mechanism is realized with the participation of intrinsic factor, which is secreted by the parietal cells of the gastric mucosa. After the release of haptocorrin under the action of gastric juice, vitamin B12 binds to intrinsic factor with the formation of a vitamin B12-intrinsic factor complex. This complex binds to a specific receptor protein on the luminal surface of the ileal mucosa.
Independent of intrinsic factor, vitamin B12 can enter the circulation by unsaturated passive diffusion. Passive diffusion can occur in all parts of the small intestine, accounts for approximately 1–2% of all absorbed vitamin B12, and is not altered in patients who have undergone gastroduodenal surgical resection or in patients with other gastrointestinal diseases that affect vitamin B12 absorption under the influence of intrinsic factor. Passive absorption plays an important role in the administration of therapeutic doses that exceed the recommended daily intake of vitamin B12 by 100 times or more.
Studies in healthy volunteers show that a maximum of 1.5 μg of orally administered vitamin B12 is absorbed with the aid of intrinsic factor. As the oral dose increases, intrinsic factor-mediated absorption reaches supersaturation and diffusion-mediated absorption increases. Approximately 90% of the cobalamin in plasma is bound to proteins (transcobalamins). In humans, vitamin B12 is stored in depots, the most important of which are the liver (about 1.5 mg), as well as in the kidneys, heart, spleen, and brain. The total body content of vitamin B12 varies, but most estimates put it at 2–3 mg. The circulation rate is 2.5 μg of vitamin B12 per day, or 0.05% of the amount in the body. The biological half-life is approximately 1 year. 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 caused by a deficiency of B vitamins.
Contraindication
Hypersensitivity to the active substances or to any of the excipients. Use in children and adolescents due to the high content of active substances. Vitamin B1 is contraindicated in patients with allergic diseases in case of hypersensitivity reaction to vitamin B1. Vitamin B6 is contraindicated in gastric and duodenal ulcers in the acute stage (since increased acidity of gastric juice is possible). Vitamin B12 is contraindicated in erythremia, erythrocytosis, thromboembolism.
Interaction with other medicinal products and other types of interactions
5-Fluorouracil. Thiamine is inactivated by 5-fluorouracil because the latter competitively inhibits the phosphorylation of thiamine to thiamine pyrophosphate.
Antacids: Antacids reduce the absorption of thiamine.
Loop diuretics: Loop diuretics such as furosemide, which inhibit tubular reabsorption, may, during long-term therapy, cause increased excretion of vitamin B1 (thiamine) and thus reduce thiamine levels.
Levodopa. When taken simultaneously with levodopa, vitamin B6 may reduce the effect of levodopa.
Pyridoxine antagonists: Concomitant administration of pyridoxine antagonists (e.g. isoniazid (INH), hydralazine, D-penicillamine or cycloserine) may reduce the effectiveness of vitamin B6 (pyridoxine).
Sulfites. Beverages containing sulfites (such as wine) increase the degradation of thiamine.
Drinking alcohol and black tea reduces thiamine absorption.
Application features
When using vitamin B12, the clinical picture, as well as laboratory tests in funicular myelosis or pernicious anemia, may lose their specificity.
Since Neurobion contains vitamin B6, it should be prescribed with caution to patients with a history of gastric and duodenal ulcers, severe liver and kidney failure.
This drug should not be used in patients with neoplasms, except in cases associated with megaloblastic anemia and vitamin B12 deficiency. The drug is not used in severe or acute forms of cardiac decompensation and angina pectoris.
If signs of peripheral sensory neuropathy (paresthesia) appear, the dosage should be reviewed and the drug discontinued if necessary. Neuropathies have been observed with long-term use (more than 6-12 months) of daily doses exceeding 50 mg of vitamin B6, as well as with short-term use (more than 2 months) of more than 1 g of vitamin B6 per day. In this regard, constant monitoring is recommended with long-term use.
This medicinal product contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product.
This medicine contains less than 1 mmol (23 mg) sodium per tablet, i.e. essentially 'sodium-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 or operating other mechanisms. This medicine has no or negligible influence on the ability to drive and use other mechanisms.
Use during pregnancy or breastfeeding
Pregnancy
During pregnancy and breastfeeding, the recommended daily intake of vitamin B1 is generally 1.4 mg and vitamin B6 is 1.9 mg. These doses may only be exceeded for pregnant women with a clear deficiency of vitamins B1 and B6, as the safety of doses higher than the recommended daily intake has not yet been demonstrated.
Animal studies on the effects of the drug on pregnancy, embryofetal, prenatal and postnatal development are insufficient. The potential risk to humans is unknown. The physician should determine the appropriateness of using the drug during pregnancy after careful consideration of the potential benefit/risk ratio.
Breast-feeding
Vitamins B1, B6 and B12 are secreted into human breast milk. High concentrations of vitamin B6 (600 mg/day) may suppress breast milk production. Animal data on the extent of secretion into breast milk are not available. A decision must be made whether to discontinue breast-feeding or to discontinue the drug taking into account the potential benefit of breast-feeding for the child and the potential benefit of therapy for the woman.
Method of administration and doses
1 film-coated tablet once daily. In some cases, the dose may be increased to one film-coated tablet three times daily.
The tablet should be swallowed whole with plenty of liquid, after eating.
The duration of use is determined by the doctor.
After a maximum of 4 weeks, it is necessary to determine the appropriateness of reducing the dose (see section "Special instructions").
Children
Do not use in children and adolescents (under 18 years of age).
Overdose
Chronic use in high doses may cause deterioration in liver enzyme activity, heart pain, and hypercoagulation.
Vitamin B1
Thiamine has a wide therapeutic range. Very high intravenous doses (more than 10 g) exhibit ganglion-blocking effects similar to those of curare and inhibit nerve impulse conduction.
Vitamin B6
The toxicity of vitamin B6 is considered very low. However, long-term use (more than 6–12 months) of vitamin B6 in doses exceeding 50 mg per day can cause peripheral sensory neuropathy. Symptoms gradually disappear after discontinuation of the vitamin.
Continuous use of vitamin B6 in doses exceeding 1 g per day for longer than two 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 described with doses exceeding 2 g per day.
Vitamin B12
After parenteral administration (in rare cases also after oral administration) of high doses, allergic reactions, eczematous skin disorders and acne-like rashes have been observed.
Adverse reactions
The adverse reactions are listed below, classified by system organ class and frequency. The assessment of adverse reactions by frequency is based on the following classification:
very common (≥ 1/10); common (≥ 1/100, <1/10); uncommon (≥ 1/1000, <1/100); rare (≥ 1/10000, <1/1000); very rare (<1/10000); not known (cannot be estimated from available data).
Immune system disorders: anaphylaxis.
Nervous system disorders: dizziness, headache, nervous excitement, malaise.
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.
Digestive system disorders: increased acidity of gastric juice.
Frequency unknown: gastrointestinal complaints such as nausea, vomiting, diarrhea, abdominal pain.
Renal and urinary disorders: Frequency unknown: chromaturia (red discoloration of urine, which occurs within the first eight hours after administration of the drug and usually disappears).
Expiration date
2 years.
Storage conditions
Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
10 tablets in a blister. 2 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
P&G Health Austria GmbH & Co. OG, Austria.
Presented in Ukraine by Dr. Reddy's Laboratories Ltd, India.
Location of the manufacturer and its business address
Hosslgasse 20, 9800 Spittal an der Drau, Austria.
