Cyanocobalamin bufus (Solution) Instructions for Use

Marketing Authorization Holder

Obnovlenie Pfc, JSC (Russia)

ATC Code

B03BA01 (Cyanocobalamin)

Active Substance

Cyanocobalamin (Rec.INN WHO registered)

Dosage Form

Cyanocobalamin bufus

Injection solution 500 mcg/1 ml: amp. 10 or 100 pcs.

Dosage Form, Packaging, and Composition

1 ml – ampoules (10) – carton packs.
1 ml – ampoules (100) – carton packs.

Clinical-Pharmacological Group

B vitamin

Pharmacotherapeutic Group

Antianemic drugs, vitamin B₁₂ (cyanocobalamin and its analogues), cyanocobalamin

Pharmacological Action

Vitamin B₁₂. In the body (mainly in the liver), it is converted into methylcobalamin and 5-deoxyadenosylcobalamin.

Methylcobalamin is involved in the conversion reaction of homocysteine to methionine and S-adenosylmethionine – key reactions in the metabolism of pyrimidine and purine bases (and, consequently, DNA and RNA).

In case of vitamin deficiency in this reaction, it can be replaced by methyltetrahydrofolic acid, while folate-dependent metabolic reactions are disrupted.

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.

Vitamin B₁₂ deficiency 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.

Pharmacokinetics

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%. C_max after subcutaneous and intramuscular administration is reached after 1 hour.

It is excreted from the liver with bile into the intestine and reabsorbed into the blood. T_1/2 is 500 days.

Excreted with normal renal function – 7-10% by the kidneys, about 50% by the intestines; with reduced renal function – 0-7% by the kidneys, 70-100% by the intestines.

Penetrates the placental barrier, into breast milk.

Indications

Conditions accompanied by vitamin B₁₂ deficiency

• B₁₂-deficiency anemia;
• As part of complex therapy for anemias (including iron deficiency, posthemorrhagic, aplastic, anemias caused by toxic substances and/or drugs).

In complex therapy for neuralgia

• Neuralgia (including trigeminal neuralgia), polyneuropathy (including alcoholic).

For prophylactic purposes

• When prescribing biguanides, para-aminosalicylic acid, ascorbic acid in high doses, pathology of the stomach and intestines with impaired absorption of vitamin B₁₂ (resection of part of the stomach, small intestine, Crohn’s disease, celiac disease, malabsorption syndrome, sprue), radiation sickness.

ICD codes

Dosage Regimen

Subcutaneously, intravenously, intramuscularly.

Subcutaneously, for B₁₂-deficiency anemia – 100-200 mcg/day every other day; for B₁₂-deficiency anemia with associated nervous system dysfunction – 400-500 mcg/day during the first week – daily, then with intervals between injections up to 5-7 days (folic acid is prescribed simultaneously); during remission the maintenance dose is 100 mcg/day 2 times a month, in the presence of neurological symptoms – 200-400 mcg 2-4 times a month.

For acute posthemorrhagic and iron deficiency anemia – 30-100 mcg 2-3 times a week; for aplastic anemia, anemias caused by toxic substances and/or drugs – 100 mcg until clinical and hematological improvement occurs.

For nervous system disorders – 200-400 mcg 2-4 times a month.

In neurology: neuralgia (including trigeminal neuralgia), polyneuropathy (including alcoholic) – 200-500 mcg every other day for 2 weeks.

For prophylactic purposes – 60-100 mcg daily for 20-30 days.

To eliminate vitamin B₁₂ deficiency, administer intramuscularly or intravenously, 1 mg daily for 1-2 weeks.

For young children with alimentary anemia and premature infants – subcutaneously, 30 mcg per day daily for 15 days.

Adverse Reactions

Allergic reactions, mental agitation, cardialgia, tachycardia, diarrhea, headache, dizziness, hypercoagulation, purine metabolism disorder.

Contraindications

• Hypersensitivity;
• Thromboembolism;
• Erythremia;
• Erythrocytosis;
• Pregnancy;
• Lactation period.

With caution

• Angina pectoris;
• Benign and malignant neoplasms accompanied by megaloblastic anemia and vitamin B₁₂ deficiency;
• Tendency to thrombosis.

Use in Pregnancy and Lactation

The drug is not recommended for use during pregnancy and breastfeeding, because B vitamins in high doses have a teratogenic effect.

Pediatric Use

Use is possible according to the dosage regimen.

Geriatric Use

Use is possible according to the dosage regimen. When used in recommended doses in elderly people, no side effects other than those listed above have been noted.

Special Precautions

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

During treatment, it is necessary to monitor peripheral blood parameters: on the 5-8th day of treatment, the reticulocyte count and iron concentration are determined.

The number of erythrocytes, hemoglobin and color index must be monitored for 1 month 1-2 times a week, and then – 2-4 times a month.

Remission is achieved when the number of erythrocytes increases to 4-4.5 million/μl, when normal erythrocyte sizes are reached, aniso- and poikilocytosis disappear, and the number of reticulocytes normalizes after the reticulocyte crisis.

After achieving hematological remission, peripheral blood control is carried out at least once every 4-6 months.

Exercise caution in persons prone to thrombosis, with angina pectoris (in lower doses, up to 100 mcg per injection).

When used in recommended doses in elderly people, no side effects other than those listed above have been noted.

Effect on the speed of reactions when driving vehicles or working with other mechanisms

No adverse effects of the drug on the ability to drive vehicles and engage in other activities requiring concentration and speed of psychomotor reactions have been reported.

However, given that the drug may cause dizziness, caution should be exercised when engaging in these activities.

Overdose

No data on overdose is available.

Drug Interactions

Pharmaceutically incompatible with ascorbic acid, salts of heavy metals (inactivation of cyanocobalamin), thiamine, pyridoxine, riboflavin (because the cobalt ion contained in the cyanocobalamin molecule destroys other vitamins).

The risk of developing allergic reactions increases when used concomitantly with thiamine.

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

Chloramphenicol reduces the hematopoietic response to cyanocobalamin.

Should not be combined with drugs that increase blood clotting.

Storage Conditions

In a light-protected place at a temperature not exceeding 15°C (59°F). Keep out of reach of children.

Shelf Life

Shelf life – 2 years.

Dispensing Status

Dispensed 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.