Medivitan (Solution) Instructions for Use

Marketing Authorization Holder

Medice Arzneimittel Putter, GmbH & Co. KG (Germany)

ATC Code

A11EA (B complex vitamins)

Active Substances

Cyanocobalamin (Rec.INN registered by WHO)

Pyridoxine (Rec.INN registered by WHO)

Folic acid (Rec.INN registered by WHO)

Dosage Form

Medivitan

Solution for intravenous and intramuscular administration: 4 ml amp. (sol. I) and 1 ml amp. (sol. II) 8 pcs. each, 5 ml double-chamber syringes 4 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and intramuscular administration transparent, red in color.

Excipients: sodium chloride 34 mg, water for injections up to 4 ml.

Solution for intravenous and intramuscular administration transparent, yellow in color.

Excipients: sodium chloride 8.75 mg, water for injections up to 1 ml.

4 ml of solution I – dark glass ampoules (4) and 1 ml of solution II – dark glass ampoules (4) – blister packs (2) – cardboard boxes.
5 ml (4 ml of solution I and 1 ml of solution II) – double-chamber syringes (1) complete with needle and plunger – blisters (4) – cardboard boxes.

Clinical-Pharmacological Group

B complex vitamins

Pharmacotherapeutic Group

Multivitamin

Pharmacological Action

The preparation contains a complex of B vitamins, which are involved in the process of hematopoiesis and are necessary for the normal functioning of the nervous system and other tissues, organs, and systems of the body.

The constituent vitamins: Pyridoxine (B₆), Cyanocobalamin (B₁₂), and Folic acid (B₉) regulate protein, carbohydrate, and fat metabolism, contribute to their normalization, and improve the function of motor, sensory, and autonomic nerves.

Pyridoxine (vitamin B₆), upon entering the body, is phosphorylated, converted into pyridoxal-5-phosphate, and is part of enzymes that carry out the decarboxylation, transamination, and racemization of amino acids, as well as the enzymatic transformation of sulfur-containing and hydroxylated amino acids. It participates in the metabolism of tryptophan (participation in the biosynthesis reaction of serotonin). Isolated pyridoxine deficiency is very rare, mainly in children on special artificial nutrition.

Cyanocobalamin (vitamin B₁₂) in the body (mainly in the liver) is converted into methylcobalamin and 5-deoxyadenosylcobalamin. Methylcobalamin participates in the reaction of converting homocysteine to methionine and S-adenosylmethionine – key reactions in the metabolism of pyrimidine and purine bases, and consequently, deoxyribonucleic (DNA) and ribonucleic (RNA) acids. In case of vitamin deficiency in this reaction, it can be replaced by methyltetrahydrofolic acid, which disrupts folate-dependent metabolic reactions. 5-deoxyadenosylcobalamin serves as a co-factor in the isomerization of L-methylmalonyl-CoA to succinyl-CoA – an important reaction in the metabolism of carbohydrates and lipids. Deficiency of vitamin B₁₂ leads to impaired proliferation of rapidly dividing cells of the hematopoietic tissue and epithelium, as well as to impaired formation of the myelin sheath of neurons.

Folic acid (vitamin B₉) is not synthesized in the human body; it comes from food and is produced by the normal intestinal microflora. It is a precursor of tetrahydrofolic acid, which participates as a co-factor of enzyme systems that carry out the transfer of one-carbon fragments (in the form of methyl, methylene, formyl, or methenyl groups) in a number of reactions of nucleotide and amino acid metabolism. It plays an important role in the regulation of proliferation, differentiation, and maturation processes of cells, including in erythropoiesis and embryogenesis.

Pharmacokinetics

Cyanocobalamin

In the blood, Cyanocobalamin binds to transcobalamins I and II, which transport it to the tissues. It is deposited mainly in the liver. Plasma protein binding is 90%. The maximum concentration in blood plasma after subcutaneous and intramuscular administration is reached within 1 hour.

It is excreted from the liver with bile into the intestine and is reabsorbed into the blood. Excreted with normal renal function – 7-10% by the kidneys, about 50% by the intestines. From 50 to 90% of cyanocobalamin administered intramuscularly or intravenously in doses from 0.1 to 1 mg is excreted by the kidneys within 48 hours.

Penetrates the placental barrier and into breast milk.

Folic acid

After intramuscular administration of 1.5 mg of folic acid, the concentration of the monosodium salt in blood plasma reaches a maximum within the first hour. The subsequent decrease in concentration occurs very quickly, so the initial level is reached after 12 hours. The maximum concentration in blood plasma of 80-87% after intramuscular administration is reached in about 1 hour. It intensively binds to plasma proteins. It is deposited and metabolized in the liver with the formation of tetrahydrofolic acid. It is excreted by the kidneys mainly in the form of metabolites.

Penetrates the blood-brain barrier, placenta, and into breast milk.

Pyridoxine

Pyridoxine is metabolized in the liver to form pharmacologically active metabolites (pyridoxal phosphate and pyridoxamine phosphate). Pyridoxal phosphate binds to plasma proteins by 90%. It penetrates well into all tissues; it accumulates mainly in the liver, less in muscles and the central nervous system. The half-life is 15-20 days. It is excreted by the kidneys (with intravenous administration – 2% with bile), and also during hemodialysis.

Penetrates the placenta and is secreted in breast milk.

Indications

• Combined deficiency of vitamins – pyridoxine, cyanocobalamin, and folic acid, in cases where it is not possible to compensate for the deficiency through diet.

ICD codes

Dosage Regimen

The preparation is administered intramuscularly or intravenously. Intramuscular administration is recommended to be deep and slow; it is necessary to alternate injection sites.

The contents of the ampoules (solution I and solution II) must be sequentially drawn into a syringe and mixed immediately before use.

Use of the preparation in pre-filled double-chamber syringes requires preliminary preparation.

Instructions for preparing the syringe for use:

1. Insert the plunger handle into the plunger hole at the back of the syringe barrel, screw it in until it stops.

2. Remove the protective cap from the syringe barrel nozzle and attach the needle.

3. Holding the syringe vertically with the needle up, slowly press the plunger until the membrane between the chambers is destroyed. Shake the syringe to mix the solutions. The preparation should be administered immediately after mixing the solutions.

Administer one dose of the preparation (5 ml) intramuscularly or intravenously 2 times a week, the course of treatment is 4 weeks (8 injections in total).

In case of impaired intestinal absorption, one dose of the preparation is recommended to be administered intramuscularly at intervals of 4 weeks.

Between injections, it is recommended to take folic acid orally daily.

Adverse Reactions

The frequency of side effects noted when taking the preparation is given in accordance with the WHO classification: very common (> 1/10), common (> 1/100 and < 1/10), uncommon (>1/1000 and < 1/100), rare (> 1/10000 and < 1/1000), very rare (<1/10000), including isolated reports.

Very rare (<0.01%) allergic reactions (skin reactions in the form of itching, urticaria), increased sweating, tachycardia, possible appearance of acne, difficulty breathing, angioedema, anaphylactic shock.

In cases of very rapid administration of the preparation, systemic adverse reactions (dizziness, headache, arrhythmia, convulsions) may occur; they may also be the result of an overdose.

If any of the side effects listed in the instructions worsen, or you notice any other side effects not listed in the instructions, inform your doctor.

Contraindications

• Hypersensitivity to the components of the preparation;
• Skin inflammatory reactions at the injection sites;
• Megaloblastic anemia;
• Thrombosis and thromboembolism;
• Children under 18 years of age (efficacy and safety of use have not been established).

Use in Pregnancy and Lactation

During pregnancy and lactation (breastfeeding), the use of the preparation is not recommended due to the lack of reliable clinical data confirming the safety of the preparation during these periods.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Special Precautions

It should be borne in mind that antibiotics can distort (give underestimated results) the results of the analysis of the concentration of folic acid in blood plasma and erythrocytes.

5 ml of the ready-to-use preparation Medivitan contains – 23 mg (less than 1 mmol) of sodium (minimum content). This should be taken into account when it is necessary to follow a salt-restricted diet (in chronic heart failure, in case of impaired renal function).

Influence on the ability to drive vehicles and mechanisms

The preparation does not affect the ability to drive vehicles and other mechanisms.

Overdose

Symptoms intensification of the symptoms of the preparation’s side effects.

Treatment symptomatic therapy.

Drug Interactions

Cyanocobalamin is pharmaceutically incompatible with ascorbic acid, salts of heavy metals (inactivation of cyanocobalamin), thiamine, riboflavin.

Pyridoxine enhances the effect of diuretics; weakens the activity of levodopa.

Isoniazid, penicillamine, cycloserine, and estrogen-containing oral contraceptives weaken the effect of pyridoxine.

With simultaneous use with chloramphenicol, neomycin, polymyxins, tetracyclines, the absorption of folic acid is reduced.

Analgesics (long-term therapy), anticonvulsants (including phenytoin and carbamazepine), estrogen-containing oral contraceptives increase the need for folic acid.

The use of folic acid may reduce the plasma concentration of phenobarbital, phenytoin, or primidone and cause an epileptic seizure.

Antacids, cholestyramine, sulfonamides (including sulfasalazine) reduce the absorption of folic acid.

The preparation Medivitan should not be taken in combination with methotrexate, pyrimethamine, triamterene, trimethoprim, since they act as antagonists of folic acid, inhibiting tetrahydrofolate reductase.

Storage Conditions

In a place protected from light, at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 3 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.