Cyanocobalamin-darnitsa (vitamin b12-darnitsa)
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CYANOCOBALAMIN-DARNITSA (VITAMIN B12-DARNITSA) (CYANOCOBALAMIN-DARNITSA) (VITAMIN B12-DARNITSA)
Composition:
active substance: cyanocobalamin;
1 ml of solution contains cyanocobalamin 0.2 mg or 0.5 mg;
excipients: sodium chloride, sodium acetate trihydrate, acetic acid, water for injections.
Pharmaceutical form. Solution for injection.
Main physicochemical properties: clear red-colored liquid.
Pharmacotherapeutic group.
Vitamin B12 (cyanocobalamin and its analogues). Cyanocobalamin. ATC code B03B A01.
Pharmacological Properties
Pharmacodynamics
Vitamin B12 (cyanocobalamin) exhibits metabolic and hematopoietic effects. In the body (primarily in the liver), it is converted into its coenzyme form—adenosylcobalamin, or cobamamide—which is the active form of vitamin B12. Cobamamide is a component of numerous enzymes, including reductase that reduces folic acid to tetrahydrofolic acid. It has high biological activity. Cobamamide participates in the transfer of methyl and other one-carbon fragments; therefore, it is essential for the formation of deoxyribose and DNA, creatine, and methionine—the donor of methyl groups—as well as for the synthesis of the lipotropic factor choline, for the conversion of methylmalonic acid into succinic acid (a component of myelin), and for the utilization of propionic acid. Cobamamide is necessary for normal hematopoiesis, as it promotes erythrocyte maturation. It participates in the synthesis and accumulation of sulfhydryl group-containing compounds in erythrocytes, thereby increasing their resistance to hemolysis. It activates the blood coagulation system and, at high doses, increases thromboplastin activity and prothrombin activity. It reduces blood cholesterol levels. It exerts a positive effect on liver and nervous system function. It enhances tissue regenerative capacity.
Pharmacokinetics
After parenteral administration, vitamin B12 rapidly enters the systemic circulation. In the blood, it binds to transcobalamins I and II, which transport it to tissues. It is predominantly stored in the liver. Plasma protein binding is 90%. The time to reach maximum concentration (TCmax) after subcutaneous or intramuscular administration is approximately 1 hour. It is excreted from the liver into bile and reabsorbed from the intestine back into the blood. The half-life (T1/2) in the liver is 500 days. Under normal kidney function, 7–10% is excreted renally and about 50% via feces; in renal impairment, 0–7% is excreted renally and 70–100% via feces. It crosses the placental barrier.
Clinical characteristics.
Indications.
Treatment of malignant, post-hemorrhagic, and iron-deficiency anemias, aplastic anemias in children, nutritional anemias caused by toxic substances and drugs, and anemias associated with vitamin B12 deficiency, regardless of the cause of deficiency (gastrectomy, helminthic infestations, impaired intestinal absorption, pregnancy). Polyneuritis, trigeminal neuralgia, radiculitis, causalgia, migraine, diabetic neuritis, amyotrophic lateral sclerosis, cerebral palsy in children, Down syndrome, alcoholic delirium. Use in children with dystrophy, following infectious diseases, in sprue (together with folic acid), in liver diseases (hepatitis, cirrhosis, Botkin's disease), radiation sickness, psoriasis, herpes-like dermatitis, neurodermatitis, and photodermatoses.
Contraindications.
Hypersensitivity to the components of the drug. Erythremia, erythrocytosis. Neoplasms, except in cases associated with megaloblastic anemia and vitamin B12 deficiency. Acute thromboembolic diseases. Severe exertional angina of high functional class.
Interaction with other medicinal products and other types of interactions.
Aminoglycosides, salicylates, antiepileptic drugs, colchicine, and potassium preparations reduce the absorption of the drug and affect its kinetics.
When used concomitantly with kanamycin, neomycin, polymyxins, and tetracyclines, absorption of cyanocobalamin is reduced.
Pharmaceutically incompatible with ascorbic acid and heavy metal salts (inactivation of cyanocobalamin); thiamine bromide, pyridoxine, riboflavin (the cobalt ion present in the cyanocobalamin molecule destroys other vitamins).
Thiamine – increased risk of thiamine-induced allergic reactions.
Chloramphenicol – reduces the hematopoietic response to the drug.
Oral contraceptives – reduce cyanocobalamin blood concentration.
Special precautions for use.
During the treatment period, it is necessary to monitor peripheral blood parameters: reticulocyte count and iron concentration should be determined on day 5–8 of treatment initiation. The number of erythrocytes, hemoglobin concentration, and color index should be monitored once or twice weekly for the first month, and thereafter 2–4 times per month. Remission is achieved when erythrocyte count reaches 4.0–4.5*1012/L, erythrocytes return to normal size, anisocytosis and poikilocytosis disappear, and reticulocyte levels normalize following the reticulocyte crisis. After achieving hematological remission, peripheral blood monitoring should be performed no less frequently than once every 4–6 months.
In case of tendency towards leukocytosis or erythrocytosis, the dose of the medicinal product should be reduced or treatment temporarily discontinued.
Cyanocobalamin must not be used concomitantly with drugs that enhance blood coagulation.
During treatment, caution is required and blood coagulation should be monitored in patients predisposed to thrombosis or suffering from angina pectoris.
Important information about excipients.
This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e. it is practically sodium-free.
Use during pregnancy or breastfeeding.
Use with caution and under physician supervision during pregnancy (there are limited data on teratogenic effects of vitamin B12 at high doses) or breastfeeding, taking into account the benefit-risk ratio.
Ability to influence reaction speed when driving or operating machinery.
During treatment, patients should refrain from driving vehicles and engaging in other potentially hazardous activities requiring heightened attention and rapid psychomotor reactions.
Administration and Dosage
The medicinal product should be administered subcutaneously, intramuscularly, or intravenously. In cases of subacute combined (funicular) myelosis and amyotrophic lateral sclerosis, it may also be administered intrathecally.
Adults
For vitamin B12-deficient anemias: administer the medicinal product at doses of 100–200 mcg (0.1–0.2 mg) every other day until remission is achieved.
In cases of funicular myelosis symptoms and macrocytic anemias with nervous system involvement: administer cyanocobalamin at a single dose of 400–500 mcg (0.4–0.5 mg) or higher. During the first week, administer daily, then every 5–7 days (folic acid should be co-administered). In severe cases, administer intraspinally, starting with a single dose of 15–30 mcg, increasing the dose at each subsequent injection (50, 100, 150, 200 mcg). Perform intrathecal injections every 3 days; a total of 8–10 injections are required per course. During remission, in the absence of funicular myelosis symptoms, use a maintenance dose of 100 mcg twice monthly. In the presence of neurological symptoms, administer 200–400 mcg 2–4 times per month.
For amyotrophic lateral sclerosis, encephalomyelitis, and neurological disorders with pain syndrome: administer the medicinal product in gradually increasing doses from 200 to 500 mcg per injection (once improvement is observed, reduce to 100 mcg daily). Treatment course duration: 14 days.
For peripheral nerve injuries: administer 200–400 mcg once every 2 days for 40–45 days.
For hepatitis and liver cirrhosis: administer 15–30 mcg daily or 100 mcg every other day for 25–40 days.
For diabetic neuropathy, sprue, and radiation sickness: administer 60–100 mcg daily for 20–30 days.
For vitamin B12 deficiency: treatment dose – 1 mg intramuscularly or intravenously daily for 1–2 weeks; maintenance dose – 1–2 mg intramuscularly or intravenously, from once weekly to once monthly. The duration of cyanocobalamin therapy and the need for repeated courses depend on the disease course and treatment efficacy.
Children
Administration is permitted only subcutaneously.
For post-hemorrhagic and iron-deficiency anemias: administer 30–100 mcg 2–3 times weekly.
For aplastic anemia in children: administer 100 mcg until clinical and hematological improvement is achieved.
For nutritional anemias in childhood: administer 30 mcg daily for 15 days.
For dystrophies in early childhood, Down syndrome, and cerebral palsy in children: administer 15–30 mcg every other day.
For hepatitis and liver cirrhosis in children: administer 15–30 mcg daily or 100 mcg every other day for 25–40 days.
Children
The dosage form with a concentration of 0.5 mg/mL must not be administered to children under 3 years of age.
Administration is permitted only subcutaneously.
Overdose
Symptoms: pulmonary edema, congestive heart failure, peripheral vascular thrombosis.
Treatment: symptomatic management.
Adverse reactions.
Gastrointestinal disorders: diarrhoea.
Metabolism and nutritional disorders: acne, bullous eruptions, nausea, sweating, purine metabolism disorders, hypokalaemia.
Nervous system disorders: headache, dizziness, nervous excitement, somnolence, muscle paralysis, loss of consciousness.
Cardiovascular disorders: tachycardia, chest pain, congestive heart failure, peripheral vascular thrombosis, low blood pressure, cardiac arrest.
Blood disorders: hypercoagulation.
Immune system disorders: allergic reactions, including skin manifestations such as erythema, urticaria, rash, pruritus, dermatitis, oedema, including Quincke's oedema; respiratory disorders, including dyspnoea attacks, anaphylactic shock, anaphylactoid reactions.
General disorders and administration site conditions: malaise, fever; at the injection site: erythema, pruritus, pain, swelling, induration, and necrosis.
Reporting of suspected adverse reactions.
Reporting suspected adverse reactions after authorization of the medicinal product is an important procedure. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national reporting system.
Shelf life. 2 years.
Storage conditions.
Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze.
Keep out of reach and sight of children.
Incompatibility.
When cyanocobalamin is used in the same solution with ascorbic acid or pyridoxine, mutual destruction of the vitamins occurs; with nicotinic acid — destruction of cyanocobalamin; with riboflavin — accumulation of cobalt ions.
Packaging.
1 ml in an ampoule; 5 ampoules in a blister pack; 2 blister packs in a carton.
Prescription status. Prescription only.
Manufacturer: JSC "Pharmaceutical Company "Darnytsia".
Manufacturer's address and place of business:
13, Borysplilska Street, Kyiv, 02093, Ukraine.