Diacobal

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DIACOBAL (DIACOBAL®)

Composition:

Active substance: methylcobalamin;

1 tablet contains 500 mcg of methylcobalamin;

Excipients: microcrystalline cellulose, pregelatinized starch, povidone K 30, colloidal anhydrous silicon dioxide, talc, stearic acid, ethylcellulose, titanium dioxide (E 171), polyethylene glycol 400, coating Opadry 03F565012 brown: hypromellose, titanium dioxide (E 171), iron oxide red (E 172), polyethylene glycol, talc.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: round, biconvex film-coated tablets of brown color.

Pharmacotherapeutic group.
Vitamin B12 preparations (cyanocobalamin and its analogs). ATC code B03B A05.

Pharmacological Properties.

Pharmacodynamics.

Methylcobalamin is one of the active forms of vitamin B12. Vitamin B12 is essential for nuclear protein and myelin synthesis, cell reproduction, normal growth, and normal erythropoiesis. Compared to other forms of vitamin B12, methylcobalamin is more efficiently transported to neuronal organelles at the subcellular level and stimulates the synthesis of proteins and nucleic acids. It is precisely due to this property that methylcobalamin is more effective in treating diseases of the nervous system.

Methylcobalamin plays an important role in transmethylation processes as a coenzyme of methionine synthase—an enzyme involved in the conversion of homocysteine to methionine in methylation reactions of proteins and DNA. Methylcobalamin is known to normalize axonal transport of protein complexes and promote axonal regeneration. Additionally, methylcobalamin supports neuronal myelination by stimulating the synthesis of phospholipids (particularly lecithin—the main lipid component of the myelin sheath of nerve endings). Furthermore, methylcobalamin restores slowed synaptic transmission and reduces neurotransmitter levels to normal.

Therapeutic doses of methylcobalamin promote detoxification processes in the nervous system by increasing the levels of tetrahydrofolate. Methylcobalamin also acts as a coenzyme in the conversion of homocysteine to S-adenosylmethionine, a universal methyl group donor, thereby enhancing transmethylation reactions.

Pharmacokinetics.

After a single oral dose administered on an empty stomach at 120 mcg and 1500 mcg in healthy adult male volunteers, peak plasma concentration of total vitamin B12 was reached within 3 hours for both doses, and this parameter was dose-dependent. Between 40% and 90% of the total amount of B12 excreted in urine within 24 hours after administration was excreted during the first 8 hours. Data are not confirmed for the single 1500 mcg dose.

With continued multiple oral administration at a dose of 1500 mcg daily over 12 consecutive weeks in healthy adult male volunteers, peak serum concentrations of total vitamin B12 were observed up to 4 weeks after the last dose. Serum concentration increased during the first 4 weeks after initiation of treatment, reaching a level approximately twice the baseline value. Thereafter, a gradual increase was observed, reaching a maximum of 2.8 times the baseline value at week 12 of treatment. Serum concentration decreased after the final dose (at week 12), but still remained 1.8 times higher than baseline 4 weeks after the last administration.

Clinical characteristics.

Indications.

Peripheral neuropathy.

Contraindications.

Known hypersensitivity to methylcobalamin or to any other components of the drug.

Erythremia, erythrocytosis.

Neoplastic diseases, except in cases associated with megaloblastic anemia and vitamin B12 deficiency.

Acute thromboembolic disorders.

High functional class angina pectoris.

Interaction with other medicinal products and other forms of interaction.

Concomitant use with folic acid improves absorption and utilization of methylcobalamin.

Other drugs containing vitamin B12 should not be administered simultaneously.

Chloramphenicol reduces the hematopoietic reticulocyte response to the drug. If such combination cannot be avoided, blood parameters must be carefully monitored.

Medicinal products which may reduce vitamin B12 absorption: aminosalicylic acid, antibiotics, colchicine, cholestyramine, H2-receptor antagonists, metformin, neomycin, nitrous oxide, phenytoin, phenobarbital, primidone, proton pump inhibitors, zidovudine.

When used concomitantly with thiamine, the risk of thiamine-induced allergic reactions increases.

Oral contraceptives reduce vitamin B12 concentration in blood.

Special precautions for use.

Diacobal should be used with caution in patients with manifestations of allergy or a history of liver disease.

Prolonged use of high doses of the drug is not recommended in patients whose professional activities are associated with mercury or mercury-containing compounds.

Vitamin B12 should not be used concomitantly with drugs that increase blood coagulation. During treatment with the drug, peripheral blood parameters should be monitored. Caution is required in patients predisposed to thrombosis and in patients with angina pectoris; blood coagulation should be monitored during treatment.

In case of tendency to develop leukocytosis or erythrocytosis, the dose of the drug should be reduced or treatment temporarily discontinued.

Use during pregnancy or breastfeeding.

There is no data available regarding the safety of using the drug during pregnancy or breastfeeding.

Ability to affect reaction rate while driving or operating machinery.

There is no data available on the negative impact of the drug on psychomotor reaction speed.

Dosage and Administration.

The medication is intended for oral use in adults.

The recommended daily dose is 1500 mcg (3 tablets), divided into three doses.

The duration of treatment depends on the nature and course of the disease and is determined individually. If there is no clinical effect after continuous use of the medication for 1 month, treatment should be discontinued.

Children.

The use of the medication is contraindicated in children (under 18 years of age).

Overdose.

Symptoms: nausea, vomiting, dizziness, excitement, tachycardia.

Treatment: symptomatic and supportive therapy.

Adverse Reactions

Gastrointestinal disorders: anorexia, nausea, vomiting, diarrhea.

Central nervous system disorders: anxiety, headache, dizziness, migraine, severe anxiety disorders, excitation, insomnia.

Cardiovascular system disorders: palpitations, tachycardia, chest pain.

Immune system disorders: hypersensitivity reactions, including urticaria, anaphylactic shock, anaphylactoid reactions.

Musculoskeletal system disorders: muscle pain, joint pain.

Skin disorders: hyperemia, pruritus, rash, acne.

Blood and lymphatic system disorders: thrombosis, hypercoagulation.

General disorders: increased sweating, general weakness, fever.

Reporting of 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 should report any suspected adverse reactions via the national reporting system and through the feedback form on the website: https://kusum.ua/pharmacovigilance/.

Shelf Life.

2 years.

Storage Conditions.

Store at a temperature not exceeding 25 ºC.

Keep out of reach and sight of children.

Packaging.

10 tablets per blister; 3 or 10 blisters per cardboard pack.

Prescription Status.

Prescription only.

Manufacturer.

LLC "KUSUM PHARM".

Manufacturer's Address and Place of Business.

40020, Ukraine, Sumy region, city of Sumy, Skryabina Street, 54.