Vitaprompt

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT VITAPROMPT®

Composition:

Active substance: cyanocobalamin;

One tablet contains 1000 mcg of cyanocobalamin (vitamin B12);

Excipients: mannitol, microcrystalline cellulose (grade: PH 102), sodium starch glycolate (type A), magnesium stearate, white film-coating mixture consisting of: hypromellose 6 mPas type 2910, hydroxypropylcellulose 100 mPas, talc, medium-chain triglycerides, titanium dioxide (E 171).

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: round, biconvex film-coated tablets of white to slightly pinkish color.

Pharmacotherapeutic group. Antianaemic agents. Cyanocobalamin.

ATC code B03B A01.

Pharmacological properties.

Pharmacodynamics.

As a cofactor of the prosthetic group of methylmalonyl-CoA mutase, vitamin B12 is required for the conversion of propionic acid into succinic acid. In addition, like folic acid, vitamin B12 also participates in the formation of labile methyl groups, which are transferred to other methyl acceptors via transmethylation processes. The vitamin also influences the synthesis of nucleic acids, particularly during hematopoiesis, as well as other cell maturation processes.

Availability and requirements

The human body is unable to synthesize vitamin B12. It is obtained from food. Products containing vitamin B12 include liver, kidneys, heart, fish, oysters, milk, egg yolks, and meat. For therapeutic purposes, vitamin B12 is administered in the form of cyanocobalamin and/or hydroxocobalamin. Both are precursors of the active substance, which the body converts into active forms—methylcobalamin and 5-adenosylcobalamin. According to data from the European Food Safety Authority (EFSA), the daily requirement of vitamin B12 for a healthy adult is 4 mcg.

Causes and signs of deficiency

Vitamin B12 deficiency may arise due to a wide range of disorders and diseases, including (autoimmune) atrophic gastritis or other inflammatory gastrointestinal conditions, malabsorption of cobalamin from food, bariatric surgery, or pancreatic insufficiency. It may also be caused by external factors such as inadequate nutrition or strict vegetarian diet, as well as in the context of long-term use of medications (e.g., metformin, aminosalicylate, antacids, or proton pump inhibitors, N2O). If chronic inability to absorb sufficient vitamin B12 from food is anticipated (e.g., pernicious anemia, post-bariatric surgery status, or other cases of chronic malabsorption, strict vegetarianism), patients should receive lifelong cyanocobalamin supplementation.

Impaired or absent absorption of vitamin B12 or reduced assimilation from food will ultimately lead to clinical symptoms if plasma concentrations fall below 200 pg/mL.

Consequences include megaloblastic anemia and neurological disturbances in the peripheral and central nervous systems. Polyneuropathy may occur along with spinal cord involvement and psychiatric disorders. Early signs of vitamin B12 deficiency include fatigue, pallor, tingling in hands and feet, unsteady gait, and reduced physical activity.

Treatment outcomes

Symptoms caused by vitamin B12 deficiency can only be resolved by administration of vitamin B12 components, particularly cyanocobalamin. In cases of severe deficiency, the preferred route of administration is parenteral, as adverse reactions caused by daily oral administration of high doses of vitamin B12 typically resolve within 1–3 months of treatment.

Pharmacokinetics.

Vitamin B12 is absorbed via two different pathways:

• Active absorption in the small intestine requires the presence of intrinsic factor (Castle's factor). Transport of vitamin B12 to tissues requires binding to transcobalamins, which are plasma beta-globulins.
• Independently of intrinsic factor (Castle's factor), vitamin B12 can also enter the bloodstream via passive diffusion through the gastrointestinal tract or through mucous membranes. Approximately 1–2% (depending on dose) of orally administered vitamin B12 reaches the bloodstream. Therefore, when high oral doses are administered (1 mg/day), sufficient absorption is achieved even in patients with intrinsic factor deficiency or those who have undergone gastrointestinal tract resection.

Up to 90% of the body's vitamin B12 stores are located in the liver, where the vitamin is stored in the form of an active coenzyme, with a daily depletion rate of 0.5 to 0.8 mcg. In healthy adults with a balanced diet, total body stores of vitamin B12 range from 3 to 5 mg. Typically, clinical signs of vitamin B12 deficiency appear 3–5 years after the onset of deficiency.

Vitamin B12 is primarily excreted in bile, and up to 1 mcg of the total excreted amount is reabsorbed daily and returned to the systemic circulation via enterohepatic circulation. If the body's storage capacity is exceeded due to high doses, particularly after parenteral administration, the unabsorbed fraction is excreted in urine.

Clinical characteristics.

Indications.

Vitaprompt®, tablets are indicated for:

• treatment of vitamin B12 deficiency due to inadequate nutrition;
• long-term treatment of vitamin B12 deficiency syndrome, for example due to malabsorption;
• oral treatment of pernicious anemia and vitamin B12 deficiency with neurological symptoms following rapid normalization of vitamin B12 blood levels using vitamin B12 injections.

Note: Initial treatment of patients requiring rapid achievement of normal vitamin B12 blood levels should be carried out with vitamin B12 injections until remission is achieved.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients listed in the section "Composition".

Vitaprompt® should not be used for treatment of megaloblastic anemia caused solely by folic acid deficiency.

Acute thromboembolic disorders. High functional class effort angina.

Vitaprompt® should not be used in patients requiring cyanide detoxification (e.g., patients with retrobulbar optic neuritis associated with pernicious anemia). In such cases, other cobalamin derivatives should be used.

Patients with vitamin B12 deficiency at risk of developing Leber's optic atrophy must not be treated with cyanocobalamin for vitamin B12 deficiency.

Vitaprompt® should not be used in patients with tobacco or alcohol amblyopia.

Interaction with other medicinal products and other types of interactions.

Absorption of vitamin B12 may be impaired when administered concomitantly with proton pump inhibitors (e.g., omeprazole), H2-receptor blockers (e.g., cimetidine), kanamycin, neomycin, polymyxins, tetracyclines, aminosalicylic acid, colchicine, antiepileptic drugs, potassium preparations, aminoglycosides (e.g., neomycin), and cholestyramine.

In patients taking metformin, serum vitamin B12 levels may be reduced.

Chloramphenicol may reduce the effect of vitamin B12 in anemia.

Prolonged exposure to nitrous oxide (laughing gas; N2O) may cause functional vitamin B12 deficiency and potentially serious neurological adverse reactions.

Second-generation antipsychotics (such as olanzapine and risperidone) are also known to potentially reduce serum vitamin B12 levels.

Glucocorticoids, such as prednisone, increase vitamin B12 absorption in patients with pernicious anemia.

Special precautions for use

At the beginning of treatment, differential diagnosis should be performed to determine whether vitamin B12 deficiency is related to dietary factors or to chronic inflammatory bowel diseases or other disorders indicating insufficient passive diffusion of vitamin B12 from food.

In patients presenting with hematological and neurological symptoms of vitamin B12 deficiency, as well as in cases where rapid normalization of vitamin B12-related biomarkers is required, treatment should be initiated with parenteral administration of cyanocobalamin. This should be continued until biochemical blood parameters normalize and clinical symptoms resolve.

Therapeutic response to oral treatment should be carefully monitored (e.g., after 7 days, then monthly, then every 6 months, and subsequently annually). To assess treatment response, plasma vitamin B12 or methylmalonic acid levels and blood count should be regularly monitored. If vitamin B12 deficiency remains unsatisfactory after 1 month, patient adherence to the treatment regimen should be evaluated, and the dose of cyanocobalamin or the route of administration should be adjusted if necessary.

Since excess cobalamin is partially excreted by the kidneys, vitamin B12 may potentially accumulate, particularly in patients with end-stage renal disease (who require dialysis). To maintain adequate serum vitamin B12 levels, serum concentrations should be monitored regularly and the treatment regimen adjusted as needed.

The drug should be used with caution in patients with concomitant folate deficiency, as folate deficiency may reduce the therapeutic response to vitamin B12 treatment. Administration of Vitaprompt® to such patients should be accompanied by treatment of folate deficiency.

Vitaprompt® contains less than 1 mmol of sodium (23 mg) per tablet, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding

Use of Vitaprompt® tablets is not recommended during pregnancy and breastfeeding.

Ability to influence reaction speed when driving or operating machinery

Unknown. Appropriate data are lacking.

Method of Administration and Dosage

Dosage

Adults

One tablet daily.

If rapid normalization of vitamin B12–related biomarkers is required, initial parenteral administration of vitamin B12 is recommended.

Elderly Patients

The standard dosage regimen is recommended for elderly patients.

Patients with Renal Impairment

Vitaprompt® can be administered at the standard dosage to patients with impaired renal function. In cases of severe renal impairment, the drug should be used under medical supervision. Serum vitamin B12 concentrations should be monitored regularly, and the dose should be reduced if necessary (see section "Special Warnings and Precautions for Use").

Patients with Hepatic Impairment

There are no pharmacokinetic data or clinical experience regarding the use of this drug in patients with impaired liver function. The safety and efficacy of this medicinal product in patients with hepatic impairment have not been studied.

Treatment Duration

Provided it is well tolerated, there are no limitations regarding the duration of use. Oral vitamin B12 is generally prescribed for lifelong administration if adequate intestinal absorption has been demonstrated, or until vitamin B12 deficiency resolves. Replacement therapy is mandatory for life in cases of pernicious anemia. Treatment response should be monitored regularly (see section "Special Warnings and Precautions for Use").

Method of Administration

Vitaprompt® tablets are administered orally, preferably on an empty stomach, with water.

Children

Vitaprompt® should not be used in children (under 18 years of age), as there is insufficient clinical data and the 1 mg dose is not appropriate for pediatric use.

Overdose

The likelihood of acute toxicity is low.

Overdose usually does not cause any symptoms, and symptomatic treatment is required only in exceptional cases.

Adverse reactions.

In the table below, all adverse reactions are listed according to system organ class and frequency of occurrence.

Reporting of suspected adverse reactions

Reporting of adverse reactions after registration of the medicinal product is of great importance. It allows continuous monitoring of the benefit/risk ratio of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of effectiveness of the medicinal product via the Automated Pharmacovigilance Information System at https://aisf.dec.gov.ua.

Shelf life. 36 months.

Storage conditions.

Store in the original packaging at a temperature not exceeding 30 ºC. Keep out of reach and sight of children.

Packaging.

10 tablets per blister; 5 blisters per carton.

Dispensing category. Over-the-counter.

Manufacturer. mibe GmbH Arzneimittel.

Manufacturer's address and place of business.

Muenchenrestrasse 15, Breuna, Saxony-Anhalt, 06796, Germany.