Cyanocobalamine (B12)

General characteristics. Structure:

Active ingredient: cyanocobalamin;

1 ml of solution contains cyanocobalamine 0,2 mg or 0,5 mg;

excipients: sodium chloride, sodium acetate trihydrate, acetic acid, water for injections.

Pharmacological properties:

Pharmacodynamics. B12 vitamin (cyanocobalamine) has metabolic, hemopoietic effect. In an organism (it is preferential in a liver) turns into a coenzymatical form – аденозилкобаламин, or Cobamamidum which is an active form of B12 vitamin. Cobamamidum is a part of numerous enzymes, including composition of the reductase recovering folic acid in tetrahydrofolic. Has high biological activity. Cobamamidum participates in transfer of methyl and other one-carbonaceous fragments therefore it is necessary for formation of desoxyribose and DNA, creatine, methionine – the donor of methyl groups, in synthesis of a lipotropic factor – sincaline, for transformation of methyl-malonic acid in amber, being a part of a myelin, for utilization of propionic acid. Cobamamidum is necessary for a normal hemopoiesis as it promotes maturing of erythrocytes. Takes part in synthesis and accumulation in erythrocytes of the connections containing sulphhydryl groups that increases their tolerance to hemolysis. Activates coagulant system of blood, in high doses causes increase in thromboplastic activity and activity of a prothrombin. Reduces cholesterol level in blood. Exerts beneficial effect on function of a liver and a nervous system. Increases ability of fabrics to regeneration.

Pharmacokinetics. At parenteral use B12 vitamin quickly comes to a system blood stream. In blood contacts transcobalamines I and II which transport it in fabric. It is deposited preferential in a liver. Communication with proteins of plasma – 90%. Time of achievement of the maximum concentration (TCmax) after hypodermic or intramuscular maintaining makes about 1 h. Out of a liver it is brought with bile in intestines and again soaked up in blood. An elimination half-life (T1/2) from a liver – 500 days. It is removed at normal function of kidneys – 7-10% by kidneys, about 50% – with a fecal masses; at reduced function of kidneys – 0-7% kidneys, 70-100% – with a fecal masses. Gets through a placental barrier.

Pharmaceutical characteristics.

Main physical and chemical properties: transparent liquid of red color.

Incompatibility. The ion of cobalt which contains in a cyanocobalamine molecule promotes destruction of ascorbic acid, Thiamini bromidum, Riboflavinum in one solution.

Indications to use:

The chronic anemias proceeding with deficit of B12 vitamin irrespective of the deficit reasons (Addison-Birmera's disease, alimentary macrocytic anemia), as a part of complex therapy of anemias (including iron deficiency, posthemorrhagic, aplastic; the anemias caused by toxic substances and/or medicines). Chronic hepatitis, cirrhosis, liver failure. Polyneuritis, radiculitis, neuralgia (including epileptiform neuralgia). Funicular myelosis, injuries of peripheral nerves, side amyotrophic sclerosis, cerebral palsy, Down syndrome. Skin diseases (psoriasis, photodermatosis, herpetiform dermatitis, atopic dermatitis). With the preventive purpose – at purpose of guanyl guanidines, p-aminosalicylic acid, ascorbic acid in high doses. At diseases of a stomach and the intestines which are followed by B12 vitamin absorption disturbance (a resection of a part of a stomach, a small bowel, a disease Krone, a Gee's disease, a sprue, to a spr). Acute radial illness.

Route of administration and doses:

Drug is used subcutaneously, intramusculary, intravenously and intralyumbalno.

At Addison-Birmera's anemia – on 100-200 mkg/days, subcutaneously every other day; at the anemias connected with deficit of B12 vitamin – on 100-200 mkg/days every other day. At anemias with the phenomena of a funicular myelosis and at macrocytic anemias with defeat of a nervous system – on 400-500 mkg in the first week – daily, then – 1 time in 5-7 days (at the same time appoint folic acid). During remission in the absence of manifestations of a funicular miyeoloz a maintenance dose – 100 mkg 2 times a month, in the presence of neurologic symptoms – on 200-400 mkg 2-4 times a month.

At an acute posthemorrhagic and iron deficiency anemia – 30-100 mkg 2-3 times a week, at aplastic anemia – on 100 mkg before kliniko-hematologic improvement.

At diseases of the central nervous system, neurologic diseases with a pain syndrome appoint in the increasing dosages – from 200 to 500 mkg, at improvement of a state – 100 mkg/days. Course of treatment 2 weeks. At traumatic defeats of a peripheral nervous system – 200-400 mkg every other day within 40-45 days.

At hepatitises and cirrhoses of a liver enter 30-60 mkg/days or 100 mkg every other day within 25-40 days.

At an acute radial illness, a diabetic neuropathy, to a spr – on 60-100 mkg daily within 20-30 days.

At a funicular myelosis, a side amyotrophic sclerosis, multiple sclerosis – intralyumbalno on 15-30 mkg, and at each injection the dose is increased (50; 100; 150; 200 mkg). Intralyumbalny injections spend each 3 days, all on a course 8-10 injections are necessary. During remission in the absence of manifestations of a funicular myelosis for a maintenance therapy appoint 100 mkg twice a month, in the presence of neurologic symptomatology – on 200-400 mkg 2-4 times a month.

 For elimination of deficit of B12 vitamin the drug is administered intramusculary or intravenously on 1 mg daily within 1-2 weeks, for prevention – once a month. Duration of treatment is defined individually.

The maximum daily dose for adults – 500 mkg.

Children. Enter subcutaneously in a dose 1 mkg/kg of body weight, the maximum daily dose – 100 mkg.

At alimentary anemia and anemia at premature children – subcutaneously 30 mkg a day daily within 15 days, aplastic anemia at children – 100 mkg before kliniko-hematologic improvement.

At dystrophic states after a disease, a Down syndrome and cerebral palsy – subcutaneously 15-30 mkg every other day.

At hepatitises and cirrhoses of a liver enter 30-60 mkg/days or 100 mkg every other day within 25-40 days.

Doses and the mode of use depend on pathology and fluctuate ranging from 30 to 100 mkg a day. The dosage form of 500 mkg/ml is not applied to children under 3 years.

Features of use:

Use during pregnancy or feeding by a breast.

With care, under observation of the doctor apply at pregnancy (there are single data on teratogenic effect of B12 vitamin in high doses) and during feeding by a breast, considering a ratio advantage/risk.

Children.

Enter subcutaneously. Doses and the mode of use depend on pathology and fluctuate ranging from 30 to 100 mkg a day. The dosage form of 500 mkg/ml is not applied to children under 3 years.

During treatment it is necessary to control indicators of peripheral blood: for 5-8 day of treatment the maintenance of reticulocytes, concentration of iron is defined. It is necessary to control quantity of erythrocytes, hemoglobin and a color indicator within 1 month 1-2 times a week, and further – 2-4 times a month. Remission is reached at increase in quantity of erythrocytes to 4 000 000-4 500 000/mkl, at achievement of the normal sizes of erythrocytes, disappearance anizo-and a poikilocytosis, normalization of maintenance of reticulocytes after reticulocytic crisis. After achievement of hematologic remission control of peripheral blood is carried out at least 1 time in 4-6 months.

At persons with tendency to a thrombogenesis and patients with stenocardia in the course of treatment it is necessary to adhere to care and to control coagulability of blood.

Ability to influence speed of response at control of motor transport or work with other mechanisms.

During treatment it is necessary to abstain from control of motor transport and occupations potentially dangerous types of activity requiring special attention and speed of psychomotor reactions.

Side effects:

Hematologic disturbances: hypercoagulation.
Cardiovascular disturbances: tachycardia, pain in heart.
From a nervous system: headache, dizziness, nervous excitement.
Disturbance of exchange processes: acne, violent rashes, nausea, perspiration, disturbance of purine exchange.
Allergic reactions: skin manifestations (urticaria, rash, itch), acute anaphylaxis.
General disturbances: indisposition, fever.
Local reactions: pain, consolidation and a necrosis in the place of an injection.

Interaction with other medicines:

Aminoglycosides, salicylates, antiepileptic drugs, colchicine, drugs of potassium reduce drug absorption, influence its kinetics. At simultaneous use with Kanamycinum, Neomycinum, polymyxins, tetracyclines absorption of cyanocobalamine decreases.

Pharmaceutical it is incompatible with ascorbic acid, salts of heavy metals (a cyanocobalamine inactivation), Thiamini bromidum, a pyridoxine, Riboflavinum (the ion of cobalt which is contained in a cyanocobalamine molecule destroys other vitamins).

Thiamin - amplifies risk of development of the allergic reactions caused by thiamin.

Chloramphenicol - reduces the hemopoietic answer to drug.

Cytamenum - at simultaneous use decreases effect of Cytamenum.

Oral contraceptives - reduce concentration of cyanocobalamine in blood.

Antimetabolites and the majority of antibiotics change results of microbiological researches of cyanocobalamine.

Contraindications:

Hypersensitivity to drug components. Erythremias, hyperglobulia. New growths, except for the cases which are followed by megaloblastny anemia and deficit of B12 vitamin. Acute thromboembolic diseases. Angina of exertion of a high functional class. Children's age up to 3 years for a dosage form which contains 500 mkg of cyanocobalamin in 1 ml.

Overdose:

At overdose are possible a fluid lungs, thrombosis of peripheral vessels. Therapy is symptomatic.

Storage conditions:

Term godnosti.2 years. To store in places unavailable to children in original packaging at a temperature not higher than 25 ° C. Not to freeze.

Issue conditions:

According to the recipe

Packaging:

On 1 ml in an ampoule; on 10 ampoules in a box; on 5 ampoules in a blister strip packaging; on the 2nd blister strip packagings in a pack.