Beduo

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BEDUO

Composition:

Active substances: pyridoxine hydrochloride, thiamine hydrochloride;

One tablet contains 100 mg of pyridoxine hydrochloride (vitamin B6) and 100 mg of thiamine hydrochloride (vitamin B1).

Excipients: hypromellose 5 mPas; talc, microcrystalline cellulose; colloidal anhydrous silicon dioxide; crospovidone, type A; magnesium stearate, plant-based; isolation film coating layer*; lacquer film coating layer**; yellowish-brown film coating mixture***; polyethylene glycol 35000.

*Composition of the isolation film coating layer: hypromellose 6 mPas; hypromellose 15 mPas; microcrystalline cellulose; stearic acid, plant-based, type 50.

**Composition of the lacquer film coating layer: hypromellose 6 mPas; microcrystalline cellulose; macrogol stearate, type I.

***Composition of the yellowish-brown film coating mixture: propylene glycol; hypromellose 3 mPas; titanium dioxide (E 171); iron oxide red (E 172); iron oxide yellow (E 172).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: yellowish-brown, biconvex, film-coated tablets.

Pharmacotherapeutic group. Medicinal products affecting metabolism. Vitamins. Vitamin B1 preparations in combination with vitamin B6 and/or vitamin B12.

ATC code A11D B.

Pharmacological properties.

Pharmacodynamics.

Thiamine and pyridoxine are essential nutrients (vitamins).

Thiamine

In the body, vitamin B1 (thiamine) is converted into biologically active thiamine pyrophosphate (TPP). TPP influences key processes of carbohydrate metabolism. As a coenzyme, thiamine pyrophosphate participates in the conversion of pyruvate to acetyl-CoA and in transketolase in the pentose phosphate cycle. Furthermore, it plays an important role in the conversion of alpha-ketoglutarate to succinyl-CoA in the citric acid cycle. Due to close interrelations in metabolism, interactions with other B-complex vitamins occur.

Vitamin B1 in its biologically active form, thiamine pyrophosphate, is widely distributed in plant and animal organisms. Plants and some microorganisms (autotrophs) synthesize thiamine. The human body does not produce thiamine. Because of rapid metabolic turnover and limited storage, thiamine must be consumed daily in sufficient amounts to meet requirements.

Total body stores of thiamine amount to approximately 30 mg, of which about 40% is located in muscle tissue. To prevent deficiency, men are recommended to consume 1.0–1.3 mg of vitamin B1 daily, adolescents up to 1.4 mg daily, and women 1.0 mg daily. During pregnancy, the daily dose should be increased by 0.2 mg, and during lactation, by 0.4 mg.

The minimal human requirement for thiamine is 0.3 mg per 1000 kcal.

Thiamine deficiency leads to avitaminosis and Wernicke's encephalopathy. Clinical symptoms of thiamine deficiency appear after 2–3 weeks of inadequate intake. Thiamine deficiency manifests primarily as symptoms affecting the peripheral nervous system, cardiovascular system, and gastrointestinal tract.

Pharmacological treatment of deficiency states requires doses higher than those used for prophylaxis.

Pyridoxine

Vitamin B6 (pyridoxine), in its phosphorylated form (pyridoxal-5'-phosphate, pyridoxal phosphate), acts as a coenzyme for several enzymes involved in non-oxidative amino acid metabolism. Phosphorylation of the CH2OH group at position 5 is a necessary condition for its function as a coenzyme.

Through decarboxylation, enzymes derived from pyridoxal phosphate participate in the formation of physiologically active amines (e.g., adrenaline, histamine, serotonin, dopamine, tyramine). Through transamination, vitamin B6, as a coenzyme of glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, gamma-aminobutyric acid, and alpha-ketoglutarate transaminase, participates in anabolic and catabolic processes in various types of amino acid breakdown and synthesis.

Vitamin B6 participates in four different stages of tryptophan metabolism. In hemoglobin synthesis, vitamin B6 catalyzes the formation of alpha-amino-beta-keto-adipic acid. Additionally, direct biochemical links exist with other B-complex vitamins.

The body content of vitamin B6 ranges from 40 to 150 mg.

Pyridoxine is stored primarily in muscle tissue in the form of pyridoxal-5'-phosphate. The requirement for vitamin B6 depends mainly on protein metabolism and increases with protein intake. The recommended intake is 0.02 mg of vitamin B6 per gram of dietary protein. To prevent possible deficiency, men require 1.5 mg of vitamin B6 daily, and women 1.2 mg daily. During pregnancy and breastfeeding, the daily dose should be increased by 0.7 mg. Doses may be higher, for example, during prolonged use of certain medications or in diseases and metabolic disorders.

Pharmacological treatment of deficiency states requires doses higher than those used for prophylaxis.

Inadequate dietary intake may lead to deficiency symptoms affecting peripheral nerves, skin, mucous membranes, and the circulatory system. In children, pyridoxine deficiency causes changes in the central nervous system.

Pharmacokinetics.

Thiamine

It is assumed that orally administered thiamine is absorbed via two dose-dependent mechanisms: active absorption for doses up to 2 µmol and passive diffusion for higher doses.

Studies using radiolabeled thiamine have shown that most absorption occurs in the duodenum, with lesser amounts absorbed in the upper and middle sections of the small intestine. Thiamine is practically not absorbed in the stomach or lower parts of the small intestine. Thiamine produced by the colonic flora is not absorbed. After oral administration of a 50 mg dose, thiamine is rapidly absorbed with a bioavailability of 5.3% in healthy individuals. Absorption after oral administration is reduced in individuals who abuse alcohol, patients with liver cirrhosis, and those with malabsorption syndromes.

Thiamine is present in all body tissues. Total body stores are estimated at approximately 30 mg. Distribution in plasma is heterogeneous: 75% of the dose penetrates erythrocytes, 15% enters leukocytes, and 10% remains in plasma, where it is primarily bound to albumin.

When thiamine levels are low, only a small amount or none at all is excreted unchanged in urine. Thiamine absorbed in excess of tissue storage capacity and coenzyme synthesis needs is rapidly excreted by the kidneys in urine, either unchanged (free or phosphorylated) or as 20–30 different metabolites containing pyrimidine and thiazole groups.

Approximately 50% is excreted unchanged or after esterification as sulfates. Other metabolites include thiamine acid, methylthiazoleacetic acid, and pyramin. Absorbed thiamine may also be converted into thiamine acid, methylthiazoleacetic acid, and pyramin.

Pyridoxine

Vitamin B6 and its derivatives (pyridoxal and pyridoxamine) are rapidly absorbed, particularly in the upper gastrointestinal tract, and are eliminated within 2–5 hours.

Absorption may be reduced in patients with malabsorption syndromes or after gastrectomy.

In plasma, approximately 60% of pyridoxine hydrochloride is converted to pyridoxal-5'-phosphate, up to 15% remains as free pyridoxine, and up to 14% as pyridoxal, predominantly bound to albumin. In blood, pyridoxal-5'-phosphate is about 80% protein-bound. In erythrocytes, it is primarily bound to hemoglobin.

Vitamin B6, bound to glycogen phosphorylase, is stored in the liver, and about 50% of its total amount is also found in muscle tissue. Pyridoxine is also stored in the brain, where it likely diffuses via a saturable mechanism.

The liver is the primary organ responsible for the metabolism of dietary pyridoxine and pyridoxamine. It has been shown that plasma concentrations of biologically active pyridoxine derivatives closely reflect pyridoxine concentrations in the liver. Pyridoxal is oxidized in the liver to 4-pyridoxic acid, which accounts for 64% of the dose excreted in urine.

The primary route of vitamin B6 elimination is renal excretion.

Clinical characteristics.

Indications.

Neurological disorders caused by proven deficiency of vitamins B1 and B6.

Note. Deficiency of vitamins B1 and B6 rarely occurs in isolation. Before starting therapy, it is necessary to check for possible deficiency of other vitamins.

Contraindications.

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

Administration of vitamin B1 is contraindicated in allergic reactions.

Administration of vitamin B6 is contraindicated in peptic ulcer of the stomach and duodenum in the stage of exacerbation (since it may increase gastric juice acidity).

Interaction with other medicinal products and other forms of interaction.

Effect on Beduo

Reduced effect

Concomitant use of pyridoxine antagonists (e.g., hydralazine, isoniazid, cycloserine, D-penicillamine) may increase the requirement for vitamin B6.

Thiamine (vitamin B1) is inactivated by 5-fluorouracil, as 5-fluorouracil exerts competitive inhibition of thiamine phosphorylation to thiamine pyrophosphate.

Antacids, alcohol, and black tea reduce thiamine absorption.

Thiamine may be destroyed if sulfite-containing beverages such as wine are consumed simultaneously.

Prolonged treatment with furosemide may lead to thiamine deficiency due to increased renal excretion.

Effect of Beduo on the action of other medicinal products

Vitamin B6 at daily doses of 5 mg or more may reduce the effect of levodopa.

Special precautions for use.

Peripheral sensory neuropathy has been observed with prolonged use of daily doses exceeding 50 mg of pyridoxine hydrochloride and with short-term use of doses exceeding 1 g/day.

If symptoms of peripheral sensory neuropathy (paresthesia) occur, the dosage should be reassessed and the drug discontinued if necessary.

Since Beduo contains vitamin B6, this medicinal product should be used with caution in patients with a history of peptic ulcer, severe liver or kidney insufficiency.

Use during pregnancy or breastfeeding.

During the second and third trimesters of pregnancy, the recommended daily intake of vitamin B1 is 1.2 to 1.3 mg.

During the first trimester of pregnancy, the recommended daily intake of vitamin B6 is 1.5 mg; during the second and third trimesters – 1.8 mg.

During breastfeeding, the recommended daily intake of vitamin B1 is 1.3 mg and of vitamin B6 is 1.6 mg.

To date, no risks have been reported with the use of vitamins B1 and B6 at recommended doses. However, systematic studies on the use of vitamins B1 and B6 in doses exceeding the recommended daily requirements are lacking. Therefore, this medicinal product should be used during pregnancy and breastfeeding only after a careful assessment of risks and benefits performed by a physician.

Vitamins B1 and B6 are excreted into breast milk.

High doses of vitamin B6 may interfere with milk production.

Ability to influence reaction speed when driving or operating machinery.

Beduo has no effect or has a negligible effect on the ability to drive a vehicle or operate machinery.

Method of Administration and Dosage

Dosage

Unless otherwise prescribed, the recommended dose for adults is 1 film-coated tablet once daily, corresponding to 100 mg of vitamin B1/vitamin B6.

Method of Administration

Beduo can be taken independently of food intake, with a sufficient amount of liquid. The film-coated tablets should not be chewed.

After four weeks of therapy, the physician should decide whether further therapeutic measures are necessary (see section "Special Warnings and Precautions for Use").

Children

The medication is not intended for use in children.

Overdose

Symptoms of Overdose

Vitamin B1 has a wide therapeutic range when administered orally. Cases of overdose have not been reported.

High doses of vitamin B6 may suppress milk production.

Prolonged administration (from several months to years) of vitamin B6 in doses exceeding 50 mg/day, as well as short-term administration (2 months) in doses exceeding 1 g/day, may lead to neurotoxic effects.

Vitamin B6 overdose primarily manifests as sensory polyneuropathy, possibly accompanied by ataxia. In cases of extremely high doses, seizures may occur. In newborns and infants, profound sedative effects, hypotension, and respiratory disorders (dyspnea, apnea) may be observed.

Treatment Measures in Case of Overdose

In the event of vitamin B6 intake exceeding 150 mg/kg body weight, induction of vomiting and administration of activated charcoal are recommended. Vomiting is most effective within the first 30 minutes after ingestion of the medication. Intensive medical treatment may be required.

Adverse reactions.

Very rare (< 1/10,000): hypersensitivity reactions (sweating, tachycardia, skin reactions with itching and urticaria). In extremely rare cases – shock.

Long-term use (from several months to years) of vitamin B6 at doses exceeding 50 mg/day, as well as short-term use (2 months) at doses exceeding 1 g/day, may cause peripheral sensory neuropathy (see section "Dosage and administration").

Gastrointestinal disorders: nausea, vomiting, diarrhea, abdominal pain, increased gastric acidity.

Endocrine system: inhibition of prolactin secretion.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance 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 efficacy via the Automated Information System for Pharmacovigilance at https://aisf.dec.gov.ua.

Shelf life. 36 months.

Storage conditions.

No special storage conditions required. Keep out of reach of children.

Packaging.

50 tablets in a bottle; 1 bottle in a carton.

Prescription status. Prescription only.

Manufacturer. mibe GmbH Arzneimittel.

Manufacturer's address and place of business.

Muenchenstrasse 15, Brehna, Saxony-Anhalt, 06796, Germany.