B12 Ankermann (Tablets) Instructions for Use

Marketing Authorization Holder

Woerwag Pharma GmbH & Co. KG (Germany)

Manufactured By

Artesan Pharma, GmbH & Co. KG (Germany)

ATC Code

B03BA01 (Cyanocobalamin)

Active Substance

Cyanocobalamin (Rec.INN registered by WHO)

Dosage Form

B12 Ankermann

Film-coated tablets 1 mg: 50 or 100 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets two-layered white, the lower one is a white film coating, the upper one is a white sugar coating; round, biconvex; on the break: the tablet core is pink with inclusions of dark pink and white.

Excipients: lactose monohydrate, povidone K 30, stearic acid, croscarmellose sodium.

Film coating composition aquapolish^® P white (hypromellose, titanium dioxide, talc, medium-chain triglycerides, stearic acid, hydroxypropylcellulose).

Sugar coating composition sucrose, talc, calcium carbonate, heavy kaolin, titanium dioxide, dried acacia dispersion, montan glycol wax, macrogol 6000, macrogol glyceryl hydroxystearate, sodium lauryl sulfate.

25 pcs. – blisters (2) – cardboard packs.
25 pcs. – blisters (4) – cardboard packs.

Clinical-Pharmacological Group

B vitamin

Pharmacotherapeutic Group

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

Pharmacological Action

Vitamin B₁₂ is part of the prosthetic group of methylmalonyl-coenzyme A-isomerase, which is necessary for the conversion of propionic acid to succinic acid.

Furthermore, vitamin B₁₂, along with folic acid, is involved in the formation of labile methyl groups, which are transferred to other methyl-acceptor proteins via transmethylation processes.

Vitamin B₁₂ affects the synthesis of nucleic acids, especially in the processes of hematopoiesis and cellular maturation in general.

For therapeutic purposes, vitamin B₁₂ is used in the form of cyanocobalamin and/or hydroxocobalamin or hydroxoacetate.

All these forms are prodrugs that are converted in the body into active forms – methylcobalamin and 5-adenosylcobalamin.

Vitamin B₁₂ is not synthesized in the human body and is supplied only with food.

Foods rich in vitamin B₁₂ include liver, kidneys, heart, fish, oysters, milk, egg yolk, and meat.

Vitamin B₁₂ is absorbed mainly in the small intestine.

Two absorption mechanisms are known: active, in which vitamin B₁₂ binds to intrinsic factor (a glycoprotein formed in the stomach), after which absorption occurs, and a passive pathway, which ensures the absorption of high doses of orally administered vitamin B₁₂ in case of intrinsic factor deficiency.

In the body, vitamin B₁₂ is stored only in an amount necessary to meet daily requirements, which is about 1 mcg.

Signs of deficiency

Reduced or absent absorption of vitamin B₁₂ from food, which can exist for several years, leads to clinical symptoms if its content in blood plasma falls below 200 pg/ml.

The hematological manifestation of deficiency is megaloblastic anemia.

The neurological 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 disorders.

Early signs of deficiency can be nonspecific symptoms, for example, weakness, pallor, paresthesia of the hands and feet, gait disturbances, and decreased physical strength.

Symptoms caused by vitamin B₁₂ deficiency can only be corrected by taking vitamin B₁₂.

When high oral doses (1 mg/day and more) are administered, remission can be achieved and successful maintenance therapy of symptoms associated with vitamin B₁₂ deficiency can be conducted.

Pharmacokinetics

Absorption of vitamin B₁₂ occurs via two pathways: active absorption in the duodenum and small intestine in a bound state with intrinsic factor (Castle’s factor); subsequent entry of vitamin B₁₂ into tissues is carried out with the help of transcobalamins, which belong to the group of plasma beta-globulins.

The second pathway is the entry of vitamin B₁₂ into the bloodstream independently of intrinsic factor through passive diffusion across the gastrointestinal mucosa.

Approximately 1-3% of orally administered vitamin B₁₂ enters the systemic bloodstream in a linear dose-dependent manner.

Thus, when taken in high doses (1 mg/day and more), sufficient absorption occurs even in patients lacking intrinsic factor.

When the requirement for vitamin B₁₂ exceeds physiological values (10 mcg/day), passive absorption of vitamin B₁₂ not associated with intrinsic factor becomes increasingly important.

As the dose increases, the total amount of absorbed vitamin B₁₂ increases in absolute terms.

The main site of vitamin B₁₂ storage is the liver.

The amount of vitamin B₁₂ used by the body to meet the daily requirement is extremely low and amounts to about 1 mcg, with a turnover rate of 2.5 mcg.

The biological T_1/2 is approximately 1 year, thus, the body uses about 2.55 mcg of vitamin B₁₂ per day, or 0.051% of the total vitamin reserve in the body.

Vitamin B₁₂ is excreted predominantly with bile, and up to 1 mcg is reabsorbed via the enterohepatic pathway.

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, its excess is excreted in the urine.

With insufficient intake of vitamin B₁₂, a critical level develops in a healthy body after 3-5 years, manifesting as signs of vitamin B₁₂ deficiency.

Indications

Treatment of vitamin B₁₂ deficiency in adults

• Due to its insufficient intake with food, prolonged imbalance of nutrition (for example, with a strict vegetarian diet);
• Due to impaired absorption as a result of malabsorption syndrome (due to insufficient production of intrinsic factor), atrophy of the gastrointestinal mucosa, use of certain medications (for example, proton pump inhibitors, histamine H₂-receptor blockers, metformin), in diseases of the terminal ileum (for example, celiac disease), blind loop syndrome, after gastrectomy or gastric bypass surgery;
• For hyperchromic megaloblastic macrocytic anemia, pernicious anemia, as well as other forms of macrocytic anemia.

ICD codes

Dosage Regimen

Administer orally at a dose of 1 mg once daily for the treatment of vitamin B₁₂ deficiency.

Swallow the tablet whole with a sufficient amount of liquid; do not chew or crush.

Take independently of meals, but at approximately the same time each day to maintain consistent serum levels.

The duration of treatment is not limited in cases of good tolerance and demonstrated therapeutic efficacy.

For patients with moderate renal impairment (e.g., CKD stage 3), the standard 1 mg daily dose may be used.

In patients with severe renal impairment (CKD stage 4 or 5, including those requiring dialysis), a dose reduction is recommended.

Monitor serum cyanocobalamin concentrations regularly in all patients with severe renal impairment to guide dose adjustments and prevent accumulation.

Initiate therapy under medical supervision, particularly for patients with severe hematological or neurological manifestations of deficiency.

Assess clinical response and adherence to therapy through regular monitoring of hematological parameters and symptom resolution.

Adverse Reactions

Skin and subcutaneous tissue disorders uncommon – severe hypersensitivity reactions, which may manifest as urticaria, rash, or itching over large areas of the body; frequency unknown – acneiform skin rash.

General disorders and administration site conditions frequency unknown – fever.

Contraindications

• Hypersensitivity to cyanocobalamin;
• Visual impairment caused by smoking or alcohol consumption (tobacco-alcohol amblyopia) or inflammation of the optic nerve (retrobulbar neuritis) due to pernicious anemia;
• Optic nerve degeneration;
• A condition requiring cyanide detoxification (in this case, other cobalamin derivatives should be taken).

Use in Pregnancy and Lactation

Cyanocobalamin is distributed to almost all tissues, including the placenta.

The recommended daily intake of cyanocobalamin during pregnancy is 4 mcg.

Existing experience with the use of higher doses of vitamin B₁₂ indicates the absence of any harmful effects on the fetus or infant.

The cyanocobalamin dosage of 1 mg is not intended for use during pregnancy.

The recommended daily intake of cyanocobalamin is 4 mcg.

Existing experience with the use of higher doses of cyanocobalamin indicates the absence of any harmful effects on the infant.

Cyanocobalamin is excreted in breast milk in concentrations close to the concentration in maternal blood.

The effect of significantly larger doses of cyanocobalamin on its concentrations in breast milk in well-nourished women has not been studied.

The cyanocobalamin dosage of 1 mg is not intended for use during breastfeeding.

Use in Hepatic Impairment

Pharmacokinetic data and clinical experience in patients with impaired liver function are not available.

Use in Renal Impairment

In patients with moderate renal impairment, Cyanocobalamin can be used at the usual dose. In severe renal impairment, a dose reduction is recommended.

Pediatric Use

Safety and efficacy in children aged 0 to 18 years have not been established to date. Data are not available.

Geriatric Use

For elderly patients, the usual dosing regimen is recommended.

Special Precautions

Patients with hematological and neurological symptoms of vitamin B₁₂ deficiency, due to the seriousness of the disease and possible consequences due to inadequate clinical response to therapy or non-compliance with the treatment regimen, require strict monitoring of the effectiveness of oral therapy.

7 days after the start of therapy, it is recommended to assess the dynamics of disease symptoms, perform a reticulocyte count, perform a complete blood count (including determining hemoglobin and hematocrit values), and also monitor the mean corpuscular volume.

Subsequently, assessment of symptoms, complete blood count results, and mean corpuscular volume should be performed every 4 weeks for the first 3 months of treatment, and then, with good adherence to treatment – once every 6-12 months.

If insufficient adherence to treatment is suspected, more frequent monitoring of therapy effectiveness, correction of the cyanocobalamin dose, or route of administration may be required.

Since excess cobalamin is excreted by the kidneys, in renal impairment Cyanocobalamin may accumulate, especially in patients with end-stage renal disease (requiring dialysis).

To maintain an adequate serum cyanocobalamin concentration, it is necessary to regularly determine the serum vitamin cyanocobalamin concentration and adjust the treatment regimen.

Cyanocobalamin 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 weaken the therapeutic response to cyanocobalamin treatment.

In such patients, the use of cyanocobalamin at a dose of 1 mg should be accompanied by treatment of folic acid deficiency.

Patients with vitamin B₁₂ deficiency who are at increased risk of developing optic atrophy should not use Cyanocobalamin for the treatment of vitamin B₁₂ deficiency.

In patients with hereditary optic atrophy (Leber’s disease), acceleration of disease progression was noted with the use of cyanocobalamin.

Drug Interactions

Absorption of vitamin B₁₂ may be impaired with the use of proton pump inhibitors (e.g., omeprazole), histamine H₂-receptor blockers (e.g., cimetidine), colchicine, aminoglycosides (e.g., neomycin), aminosalicylic acid, antiepileptic drugs, potassium salts, methyldopa, as well as against the background of alcohol intake.

When taking oral contraceptives, metformin, and antipsychotic drugs (such as olanzapine and risperidone), the serum concentration of vitamin B₁₂ may be reduced.

Chloramphenicol may weaken the effect of vitamin B₁₂ in anemia.

Long-term exposure to nitrous oxide can cause functional vitamin B₁₂ deficiency and possible serious neurological side effects even with normal vitamin B₁₂ values.

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.