B12 Anckermann, 1 mg 50 pcs

Pharmacotherapeutic group: anti-anemic drugs, vitamin B₁₂ (cyanocobalamin and its analogues), cyanocobalamin.

ATC code: B03BA01

Vitamin B₁₂ is part of the methylmalonyl-coenzyme A isomerase prosthetic group, necessary to convert propionic acid to succinic acid. In addition, vitamin B₁₂ along with folic acid participates in the formation of labile methyl groups, which are transferred to other methylacceptor proteins via transmethylation processes. Vitamin B₁₂ influences nucleic acid synthesis, especially in the processes of hematopoiesis and cell maturation in general.

Therapeutically, vitamin B₁₂ is used as cyanocobalamin, and/or hydroxocobalamin or hydroxoacetate. All of these forms are prodrugs that are converted in the body to the active forms, methylcobalamin and 5-adenosylcobalamin.

In the human body, vitamin B₁₂ is not synthesized and comes only with food. Vitamin B₁₂ is rich in liver, kidney, heart, fish, oysters, milk, egg yolk and meat. Vitamin B₁₂ is absorbed mainly in the small intestine. Two mechanisms of absorption are known: an active pathway in which vitamin B₁₂ binds to an internal factor (a glycoprotein formed in the stomach), after which absorption occurs, and a passive pathway that provides absorption of high doses of orally ingested vitamin B₁₂ in case of a lack of internal factor. Vitamin B₁₂ is stored in the body only in the amount needed to meet daily requirements, which is about 1 mcg.

Signs of deficiency

Decreased or absent absorption of vitamin B₁₂ with food, which can exist for several years, leads to clinical symptoms if its plasma levels fall below 200 pg/mL. The hematologic manifestation of the deficiency is megaloblastic anemia. The neurologic manifestation of vitamin B₁₂ deficiency is disorders of the peripheral and central nervous system. Polyneuropathy phenomena may be accompanied by damage to the posterior columns of the spinal cord and combined with psychological disturbances. Early signs of deficiency may be non-specific symptoms, such as weakness, pallor, paresthesias of the hands and feet, gait disturbances, and decreased physical strength.

The symptoms caused by vitamin B₁₂ deficiency can be corrected by vitamin B₁₂ supplementation alone. When high oral doses (1 mg/day or more) are given, remission can be achieved and successful maintenance therapy for symptoms associated with vitamin B₁₂ deficiency is provided.

The absorption of vitamin B₁₂ occurs in two ways:

• active absorption in the 12-pericardium and small intestine in a bound state with internal Castle factor. Subsequent entry of vitamin B₁₂ into tissues is by transcobalamin belonging to the group of plasma beta-globulins.
• The entry of vitamin B₁₂ into the bloodstream is independent of the internal factor by passive diffusion through the mucosa of the gastrointestinal tract. Approximately 1-3% of orally ingested vitamin B₁₂ enters the systemic bloodstream in a linear dose-dependent manner. Thus, when high doses (1 mg/day or more) are taken, sufficient absorption occurs even in patients with no intrinsic factor.

When vitamin B₁₂ requirements exceed physiologic values (10 mcg/day), passive absorption of vitamin B₁₂ not related to the internal factor is increasingly important (Table 1).

Table 1. Amount of absorbed vitamin B₁₂ as a function of dose.

The total amount of absorbed vitamin B₁₂ in absolute terms increases with increasing dose.

The main place of deposition of vitamin B₁₂ is the liver. The amount of vitamin B₁₂ used by the body to supply the daily requirement is extremely low at about 1 mcg, with a metabolic rate of 2.5 mcg. The biological half-life is about 1 year, so the body uses about 2.55 mcg of vitamin B₁₂ per day, or 0.051% of the total vitamin supply in the body.

Vitamin B₁₂ is excreted primarily with bile, and up to 1 µg is reabsorbed by the enterohepatic route. If due to the use of high doses, especially after parenteral administration, the intake of vitamin B₁₂ exceeds the body’s ability to accumulate it, the excess is excreted in the urine.

When insufficient intake of vitamin B₁₂ by a healthy body, a critical level develops after 3-5 years, manifested by signs of vitamin B₁₂ deficiency.

Preclinical Safety Data

In preclinical animal studies, there were no signs of toxicity even when administered at high doses. There were no adverse effects of vitamin B₁₂ on pre- and postnatal development when used in male and female animals and no teratogenic, mutagenic or carcinogenic effects.

Indications

The drug B12 Ankermann is indicated for the treatment of vitamin B12 deficiency in adults:

Composition

Active ingredient: cyanocobalamin

List of excipients:

The core of the tablet:

Lactose monohydrate

Povidone K 30

Stearic acid

Sodium croscarmellose

Shell composition:

Aquapolish® P white (hypromellose, titanium dioxide, talc, medium-chain triglycerides, stearic acid, hydroxypropylcellulose)

Sugar shell composition:

Sucrose

Talc

Calcium carbonate

Heavy kaolin

Titanium dioxide

Acacia dried dispersion

Montanglicol wax

Macrogrol 6000

Macroglycerol hydroxystearate

Sodium lauryl sulfate

How to take, the dosage

Dosing regimen

Adults

1 tablet (1 mg of cyanocobalamin) per day.

In severe hematologic and neurologic symptoms, parenteral administration of vitamin B12 is recommended until blood levels normalize.

If well tolerated, the duration of treatment is not limited. If there is sufficient absorption from the intestine and ongoing vitamin B12 deficiency, oral vitamin B12 preparations may be prescribed for life. The therapeutic effect of the drug must be confirmed by regular examinations (see section 4.4, Special Precautions and Precautions for Use).

Special patient groups

Elderly patients

The usual dosing regimens are recommended for elderly patients.

Patients with impaired renal function

In patients with moderate B12 renal impairment, Ankermann can be used at the usual dose. In patients with severe renal insufficiency, dose reduction is recommended and serum vitamin B12 concentrations should be monitored regularly.

Patients with impaired liver function

Pharmacokinetic data and clinical experience with use in patients with impaired liver function are not available. Safety and efficacy in patients with hepatic impairment have not been established.

Children

The safety and effectiveness of B12 Anckermann in children aged 0 to 18 years has not been established at this time. No data are available.

Method of administration

The coated tablets are taken orally, with a little liquid, without chewing, preferably in the morning on an empty stomach.

Interaction

Vitamin B12 absorption may be impaired when using proton pump inhibitors (e.g., omeprazole), H2 blockers-histamine receptor blockers (e.g., cimetidine), colchicine, aminoglycosides (e.g., neomycin), aminosalicylic acid, antiepileptic drugs, potassium salts, methyldopa, and with alcohol.

The serum concentration of vitamin B12 may be decreased when taking oral contraceptives, metformin and antipsychotic drugs (such as olanzapine and risperidone).

Chloramphenicol may weaken the effects of vitamin B12 in anemia.

Long-term exposure to nitric oxide may cause functional vitamin B12 deficiency and possible serious neurologic side effects even when vitamin B12 values are normal.

Special Instructions

Patients with hematologic and neurologic symptoms of vitamin B deficiency12 due to the severity of the disease and the possible consequences due to inadequate clinical response to therapy or patient non-compliance with treatment, close monitoring of the effectiveness of oral therapy is required. Seven days after the start of therapy, it is recommended to assess the disease symptom progression, perform a reticulocyte count, perform a complete blood count (including hemoglobin and hematocrit values), and monitor the average red blood cell volume. Thereafter, the symptoms, the results of the general blood count and the average red blood cell volume should be evaluated every 4 weeks during the first 3 months of treatment, and then once every 6-12 months if the adherence to treatment is good. If adherence is suspected to be poor, more frequent monitoring of therapy efficacy and adjustment of cyanocobalamin dose or route of administration may be necessary.

Since excess cobalamin is excreted through the kidneys, vitamin B12 may accumulate in renal failure, especially in patients with terminal renal failure (requiring dialysis). To maintain adequate vitamin B12 serum concentrations, serum vitamin B12 concentrations should be determined regularly and the treatment regimen adjusted.

Vitamin B12 should not be used to treat megaloblastic anemia caused solely by folic acid deficiency.

Caution should be exercised in patients with concomitant folic acid deficiency. Folic acid deficiency may impair the therapeutic response to vitamin B12 treatment. In such patients, use of B12 Ankermann should be accompanied by treatment of folic acid deficiency.

Patients with vitamin B12 deficiency who are at increased risk of optic atrophy should not use cyanocobalamin to treat vitamin B12 deficiency. In patients with hereditary optic atrophy (Leber’s disease), an acceleration of disease progression has been noted when using cyanocobalamin.

The B12 drug Ankermann contains lactose (as monohydrate). Patients with rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this drug.

Patients with B12 Ankermann contains sucrose. Patients with rare hereditary fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltase deficiency should not take this drug.

Influence on ability to drive and operate machinery

Ankermann B12 does not affect the ability to drive or operate machinery.

Synopsis

The film-coated tablets.

Circular biconvex tablets, coated with a two-layer coating of white, the lower one is a film coating of white, the upper one is sugar white. On the break: the core of the tablet is pink with flecks of dark pink and white.

Contraindications

Overdose

Pregnancy use

Pregnancy

Vitamin B12 is distributed to almost all tissues, including the placenta. The recommended daily intake of vitamin B12 during pregnancy is 4 mcg. Experience with higher doses of vitamin B12 indicates no harmful effects on the fetus or infant.

Controlled clinical studies of the use of high doses of vitamin B12 in pregnant women have not been conducted. Studies in animals showed no direct or indirect adverse effects with respect to reproductive toxicity (see section 5.3 Preclinical safety data).

This dosage of cyanocobalamin (1 mg) is not indicated for use during pregnancy.

Lactation

The recommended daily intake of vitamin B12 during lactation is 4 mcg. Experience with higher doses of vitamin B12 indicates no harmful effects on the infant.

There have been no controlled clinical studies in breastfeeding women.

Vitamin B12 is excreted with breast milk at concentrations close to those in maternal blood. Several studies have shown no or limited increase in vitamin B12 concentrations in breast milk after a 2-fold dose with food based on the recommended daily requirement in normally nourished women. The effect of significantly higher doses of vitamin B12 on its concentrations in breast milk in properly nourished women has not been studied.

This dosage of cyanocobalamin (1 mg) is not intended for use during lactation.

Fertility

Vitamin B12 is essential for maintaining fertility in males. Studies in male rats have found negative effects of vitamin B12 deficiency at different stages of development on fertility.

In a prospective cohort study, no association was found between folate and vitamin B12 levels and the likelihood of successful pregnancy.

No adverse fertility effects are expected for B12 Ankermann.