Neurorubin™-fortе lactab

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Neurorubine™-Forte Lactab

Composition:

Active substances: thiamine nitrate (vitamin B1), pyridoxine hydrochloride (vitamin B6), cyanocobalamin (vitamin B12);

1 film-coated tablet contains thiamine nitrate (vitamin B1) 200 mg, pyridoxine hydrochloride (vitamin B6) 50 mg, cyanocobalamin (vitamin B12) 1 mg;

Excipients: methylcellulose, mannitol (E 421), powdered cellulose, microcrystalline cellulose, pregelatinized starch, magnesium stearate, colloidal anhydrous silicon dioxide, hypromellose, macrogol 6000, talc, titanium dioxide (E 171), erythrosine (E 127).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: pink, round, biconvex film-coated tablets with "TP" imprint on one side.

Pharmacotherapeutic group. Vitamin B1 in combination with vitamin B6 and/or vitamin B12. ATC code A11D B.

Pharmacological properties.

Pharmacodynamics.

Neurorubin™-Fortе Lactab combines high doses of three vitamins: B1, B6, and B12, which play an important role in normal nervous system function. Each of these vitamins is essential for ensuring optimal metabolism in nerve cells. In addition, when administered in high doses, these vitamins exhibit analgesic effects.

Like all other vitamins, they are essential nutrients that cannot be synthesized directly in the body.

Therapeutic administration of vitamins B1, B6, and B12 replenishes insufficient dietary intake, thereby ensuring adequate levels of coenzymes in the body. B vitamins are components of enzyme systems that regulate the metabolism of proteins, fats, and carbohydrates. However, each of the B vitamins performs a specific biological role. Their presence in the body in balanced amounts is necessary for normal metabolic function.

Therapeutic use of these vitamins in various neurological disorders is aimed, on one hand, at compensating for existing deficiencies (possibly due to increased demand caused directly by the disease), and on the other hand, at stimulating natural recovery mechanisms.

Vitamins B1, B6, and B12 have very low toxicity and pose no potential risk to humans. Currently, there are no data indicating carcinogenic, mutagenic, or teratogenic properties of these vitamins.

Pharmacokinetics.

Thiamine nitrate (vitamin B1) is absorbed in the small intestine, duodenum, and colon via an active transport system. After administration, the active substance penetrates through the intestinal mucosa and then enters the liver via the portal vein. A portion of absorbed thiamine participates in enterohepatic recirculation. The main excretion products of thiamine are thiamine carboxylic acid and pyramin (2,5-dimethyl-4-aminopyrimidine), along with a relatively small amount of unchanged thiamine excreted in urine.

Pyridoxine hydrochloride (vitamin B6) is rapidly absorbed in the intestine. In the body, pyridoxine is oxidized to pyridoxal or aminated to pyridoxamine. Its function as a coenzyme requires phosphorylation of the CH2OH group at the 5th position, forming pyridoxal-5-phosphate (PLP). In blood, approximately 80% of PLP is protein-bound. Pyridoxine is primarily stored in muscles as PLP. The main excretion product is 4-pyridoxic acid.

Cyanocobalamin (vitamin B12). In healthy individuals, absorption of cyanocobalamin is limited and depends on the concentration of "intrinsic factor of Castle." A small amount of vitamin B12 is absorbed in the free form, but the majority is absorbed only after binding to "intrinsic factor of Castle."

After intestinal absorption, vitamin B12 binds in blood serum to specific proteins: vitamin B12-binding beta-protein (transcobalamin) and vitamin B12-binding alpha1-globulin. Vitamin B12 is primarily stored in the liver. The elimination half-life from plasma is 5 days, and from the liver—approximately one year.

Clinical characteristics.

Indications.

Adjunctive therapy for pain syndromes caused by:

• acute or chronic neuritis, polyneuritis, and neuralgias;
• toxic damage to nervous tissue in alcoholism, diabetic polyneuropathy, and drug intoxication.

Contraindications.

Hypersensitivity to any component of the drug.

Vitamin B1 is contraindicated in allergic diseases.

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

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

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.

The toxicity of isoniazid may be increased.

Antacids, alcohol, and tea slow down the absorption of vitamin B1.

Loop diuretics, such as furosemide, which inhibit tubular reabsorption, may during long-term therapy lead to increased excretion of thiamine and thus reduce thiamine levels.

Concomitant use with pyridoxine antagonists (e.g. isoniazid, hydralazine, penicillamine, or cycloserine) and oral contraceptives may increase the requirement for vitamin B6.

Pyridoxine may reduce the efficacy of altretamine.

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

Special precautions.

Hypersensitivity to vitamins B1, B6, and B12 may result in skin and subcutaneous tissue reactions during therapy.

Pyridoxine may provoke acne or acneiform skin eruptions, or exacerbate existing conditions.

When administering vitamin B12, the clinical picture as well as laboratory findings in funicular myelosis or pernicious anemia may lose their specificity.

Alcohol and black tea consumption reduces thiamine absorption.

Drinks containing sulfites (e.g., wine) increase thiamine degradation.

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

The drug should not be administered to patients with neoplasms, except in cases associated with megaloblastic anemia and vitamin B12 deficiency.

The drug is contraindicated in severe or acute uncompensated cardiac insufficiency and angina pectoris.

Use during pregnancy or breastfeeding.

The drug may be prescribed only after careful assessment of the benefit-risk ratio, due to insufficient data on the safety of the drug during pregnancy.

Vitamins B1, B6, and B12 are excreted in breast milk. High concentrations of vitamin B6 may suppress milk production. Studies on the extent of vitamin secretion into breast milk have not been conducted. The decision regarding discontinuation of breastfeeding or use of the drug should be made considering the importance of the drug for the mother. If use of the drug becomes necessary, breastfeeding should be discontinued during this period.

Ability to affect reaction rate when driving or operating machinery.

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

If dizziness occurs during treatment with the drug, patients should refrain from driving or operating machinery.

Method of Administration and Dosage.

Take orally before or during meals, without chewing, with sufficient amount of water. The usual dose for adults is 1–2 tablets per day. The treatment course is 4 weeks. For further treatment, consult a physician.

Children.

The drug should not be administered to children due to lack of experience in pediatric practice.

Overdose.

Vitamin B1: has a wide therapeutic range. Very high doses (more than 10 g) exhibit curare-like effects, suppressing nerve impulse conduction.

Vitamin B6: has very low toxicity.

Neuropathies have been observed with prolonged intake (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.

Neuropathies with ataxia and sensory disturbances, cerebral seizures with EEG changes, and in individual cases hypochromic anemia and seborrheic dermatitis have been reported after administration of

2 g per day. Therefore, regular monitoring is recommended during long-term use.

Vitamin B12: following parenteral administration (and in rare cases after oral administration) 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 hypercoagulation.

Treatment for oral intoxication: elimination of the toxic substance (induce vomiting, gastric lavage), measures to reduce absorption (administration of activated charcoal).

Adverse reactions.

Immune system side effects: hypersensitivity reactions, anaphylactic shock, anaphylaxis. Allergic reactions occur quite rarely.

Endocrine system side effects: inhibition of prolactin secretion.

Nervous system side effects: feeling of anxiety; long-term use (over 6–12 months) of vitamin B6 at doses exceeding 50 mg daily may lead to peripheral sensory neuropathy, nervous overexcitement, malaise, dizziness, headache.

Cardiovascular system side effects: tachycardia, collapse.

Respiratory system, thoracic and mediastinal side effects: cyanosis, pulmonary edema, respiratory disturbances.

Gastrointestinal side effects: gastrointestinal disorders, including nausea, vomiting, diarrhea, abdominal pain, increased gastric acidity, hemorrhage.

Hepatobiliary side effects: when used in high doses, increased serum glutamic-oxaloacetic transaminase (SGOT) levels.

Skin and subcutaneous tissue side effects: rash, skin reactions, including pruritus, urticaria, common acne, acneiform eruptions, erythema multiforme.

Renal and urinary system side effects: chromaturia.

Other adverse effects: increased sweating, feeling of weakness, dizziness, malaise, sensation of tightness in the throat.

Shelf life. 2 years.

Storage conditions. Store at a temperature not exceeding 25 °C in a place inaccessible to children.

Packaging.

10 film-coated tablets in a blister pack, 2 blisters per cardboard box.

Availability category. Over-the-counter.

Manufacturer. Acino Pharma AG.

Manufacturer's address and place of business.

Birsstrasse 2, 4253 Liestal, Switzerland.