Methylcobalamin (Solution) Instructions for Use

Marketing Authorization Holder

Novosibkhimpharm, JSC (Russia)

ATC Code

B03BA05 (Mecobalamin)

Active Substance

Mecobalamin (Rec.INN registered by WHO)

Dosage Form

Methylcobalamin

Solution for injection 0.5 mg/ml

Dosage Form, Packaging, and Composition

Solution for injection

2 ml – ampoules (10 pcs.) – cardboard packs – By prescription
2 ml – ampoules (20 pcs.) – cardboard packs – By prescription
2 ml – ampoules (5 pcs.) – cardboard packs – By prescription

Pharmacotherapeutic Group

Antianemic drugs; vitamin B12 and folic acid; vitamin B12 (cyanocobalamin and its analogues)

Pharmacological Action

Mecobalamin is well transported to the organelles of nerve cells and promotes the synthesis of nucleic acids and proteins. Mecobalamin is transported to the organelles of nerve cells better than cyanocobalamin (in rats). It acts as a coenzyme in the synthesis of methionine from homocysteine.

Experiments on brain cells and spinal cord cells demonstrated that Mecobalamin is involved in the synthesis of thymidine from deoxyuridine, promoting the synthesis of nucleic acids and proteins.

Mecobalamin promotes axonal transport of protein complexes and promotes axon regeneration. Mecobalamin normalized the axonal transport of protein complexes in the sciatic nerve cells of rats with streptozotocin-induced diabetes mellitus.

Neurological and electrophysiological studies revealed that Mecobalamin has an inhibitory effect on nerve fiber degeneration in neuropathies induced by drugs such as adriamycin, acrylamide, and vincristine (in rats and rabbits), as well as in models of axon degeneration in mice and neuropathies in rats with spontaneous diabetes mellitus.

Mecobalamin promotes myelination of neurons by stimulating the synthesis of phospholipids. Mecobalamin promotes the synthesis of lecithin, the main lipid of the myelin sheath, by increasing the activity of methionine synthase, thereby promoting myelination.

Mecobalamin restores delayed synaptic transmission and reduces neurotransmitter levels to normal. Mecobalamin restores the end-plate potential by increasing the excitability of nerve fibers in the crushed sciatic nerve (in rats).

In addition, Mecobalamin normalizes the reduced level of acetylcholine in the brain of rats fed a choline-deficient diet.

Mecobalamin promotes the maturation and division of erythroblasts, leading to a positive effect in anemia. Mecobalamin promotes the synthesis of nucleic acids in bone marrow cells, thereby improving the maturation and division of erythroblasts, which ultimately leads to increased red blood cell production.

Mecobalamin leads to rapid recovery of reduced levels of leukocytes, hemoglobin, and hematocrit in vitamin B₁₂-deficient rats.

Pharmacokinetics

After a single intramuscular or intravenous administration of a 500 mcg dose, the time to reach C_max of vitamin B₁₂ in the blood serum was 0.9 hours and 3 minutes, respectively.

The increase (excluding endogenous total B12 in the blood serum) in C_max was 22.4 ng/ml after intramuscular administration and 85 ng/ml after intravenous administration. AUC_0-144 was 204.1 ng×h/ml after intramuscular administration and 358.6 ng×h/ml after intravenous administration.

On the other hand, over 144 hours after administration, the increase in the saturation rate was comparable with both intramuscular and intravenous administration.

With intravenous administration of mecobalamin at a dose of 500 mcg/kg/day for 10 days. The total concentration of vitamin B₁₂ in the serum, determined before administration, increased with each day.

On day 2 of administration, the total concentration of vitamin B₁₂ in the blood serum was 5.3 ± 1.8 ng/ml, which was 1.4 times higher than the values obtained 24 hours after the first administration (3.9 ± 1.2 ng/ml).

On day 3, the concentration increased to 6.8 ± 1.5 ng/ml, which was 1.7 times higher than 24 hours after the first administration, and this concentration was maintained until the last dosing.

Vitamin B₁₂ is largely bound to specific plasma proteins – transcobalamins. Transcobalamin II appears to be involved in the rapid transport of cobalamins to tissues. Vitamin B12 accumulates in the liver. Vitamin B12 crosses the placental barrier and is excreted in breast milk.

T_1/2 was 27.1 and 29 hours after a single intravenous or intramuscular administration of mecobalamin at a dose of 500 mcg, respectively.

Vitamin B₁₂ is excreted in the bile and undergoes extensive enterohepatic recirculation; part of the administered dose is excreted in the urine, mainly within the first 8 hours.

However, urinary excretion accounts for only a small part of the reduction in vitamin B₁₂ stores in the body obtained from nutrition.

Indications

Treatment of peripheral neuropathy; treatment of megaloblastic anemia caused by vitamin B₁₂ deficiency.

ICD codes

Dosage Regimen

Administer intramuscularly or intravenously only.

The usual adult dose is 500 mcg (0.5 mg) administered once daily.

For peripheral neuropathy, administer 500 mcg daily for a minimum of 4 weeks. Adjust the regimen based on clinical response and tolerability.

For megaloblastic anemia due to vitamin B12 deficiency, administer 500 mcg three times per week.

After hematological parameters normalize, transition to a maintenance dose of 500 mcg every 1 to 3 months.

Confirm vitamin B12 deficiency diagnostically before initiating treatment.

Monitor peripheral blood parameters; on days 5-8 of treatment, determine the reticulocyte count and iron concentration.

Discontinue therapy if there is no clinical or hematological improvement within one month.

This medication is contraindicated in patients under 18 years of age.

Adverse Reactions

Immune system disorders rarely – hypersensitivity (rash); frequency unknown – anaphylactic reaction, including arterial hypotension and difficulty breathing.

Metabolism and nutrition disorders rarely – increased alkaline phosphatase activity.

Nervous system disorders rarely – headache, taste disturbance.

Gastrointestinal disorders rarely – nausea, vomiting.

Hepatobiliary disorders infrequently – increased ALT, AST activity; rarely – increased GGT activity.

General disorders and administration site conditions rarely – feeling of heat, fatigue, malaise; frequency unknown – sweating.

Administration site conditions frequency unknown – pain at the injection site, redness at the intramuscular injection site.

Contraindications

Hypersensitivity to mecobalamin; thromboembolism; erythremia; erythrocytosis; pregnancy (there are separate reports of possible teratogenic effects of B vitamins in high doses), breastfeeding period.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Special Precautions

Vitamin B₁₂ deficiency must be diagnostically confirmed before prescribing mecobalamin, as it may mask folic acid deficiency.

During treatment, peripheral blood parameters must be monitored: on days 5-8 of treatment, the number of reticulocytes and iron concentration are determined.

If there is no effect within a month, the use of mecobalamin should be discontinued.

Drug Interactions

Aminoglycosides, salicylates, antiepileptic drugs, colchicine, potassium preparations reduce the absorption of mecobalamin.

Taking mecobalamin enhances the development of allergic reactions caused by thiamine.

Chloramphenicol reduces the hematopoietic response.

The use of mecobalamin should not be combined with drugs that increase blood clotting.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.