Milgamma compositum, 100 mg+100 mg 60 pcs.

Pharmacotherapeutic group: vitamins.

ATC code: A11DB02

Pharmacological properties

Pharmacodynamics:

Benfothiamine, a fat-soluble derivative of thiamine (vitamin B1), is phosphorylated in the body to the biologically active coenzymes thiamine diphosphate and thiamine triphosphate. Thiamine diphosphate is a coenzyme of pyruvate decarboxylase, 2-oxyglutarate dehydrogenase and transketolase, thus participating in the pentose phosphate cycle of glucose oxidation (in the transfer of the aldehyde group).

The phosphorylated form of pyridoxine (vitamin B6), pyridoxalphosphate, is a coenzyme of several enzymes that affect all stages of non-oxidative metabolism of amino acids. Pyridoxal phosphate is involved in the decarboxylation of amino acids and therefore in the formation of physiologically active amines (e.g., adrenaline, serotonin, dopamine, tyramine). Pyridoxal phosphate is involved in anabolic and catabolic processes (e.g. as a coenzyme of such transaminases as glutamate oxalocetate transaminase, glutamate pyruvate transaminase, GABA, α-ketoglutarate transaminase) as well as in various amino acid degradation and synthesis reactions. Vitamin B6 is involved in 4 different steps of tryptophan metabolism.

Pharmacokinetics:

When taken orally, most of benfothiamine is absorbed in the duodenum, less in the upper and middle small intestine. Benfotiamine is absorbed due to active resorption at concentrations ≤ 2 µmol and due to passive diffusion at concentrations ≥2 µmol. As a fat-soluble derivative of thiamine (vitamin B1), benfothiamine is absorbed faster and more completely than water-soluble thiamine hydrochloride. In the gut, benfothiamine is converted to S-benzoylthiamine as a result of dephosphorylation by phosphatases. S-benzoylthiamine is fat-soluble, has high permeability and is absorbed mostly without being converted into thiamine. Due to enzymatic debenzoylation after absorption, thiamine and biologically active coenzymes thiamine diphosphate and thiamine triphosphate are formed. Especially high levels of these coenzymes are observed in the blood, liver, kidneys, muscles and brain.

Pyridoxine (vitamin B6) and its derivatives are absorbed primarily in the upper gastrointestinal tract by passive diffusion. In serum, pyridoxalphosphate and pyridoxal are bound to albumin. Before penetrating the cell membrane, pyridoxal phosphate bound to albumin is hydrolyzed by alkaline phosphatase to form pyridoxal.

The two vitamins are excreted mainly in the urine. Approximately 50% of thiamine is excreted unchanged or as sulfate. The remainder consists of several metabolites, among which are thiaminic acid, methylthiazo-acetic acid and pyramine. The average blood elimination half-life (t½) of benfothiamine is 3.6 h. The half-life of pyridoxine when taken orally is approximately 2-5 hours. The biological half-life of thiamine and pyridoxine is approximately 2 weeks.

Indications

Neurological diseases with confirmed vitamin B1 and B6 deficiency.

Composition

1 film-coated tablet contains:

active ingredients: benfothiamine 100 mg,

pyridoxine hydrochloride 100 mg.

excipients:

The composition of the core of the coated tablet: Microcrystalline cellulose – 222.0 mg, povidone (K=30 value) – 8.0 mg, high chain partial glycerides – 5.0 mg, colloidal silicon dioxide – 7.0 mg, croscarmellose sodium – 3.0 mg, talc – 5.0 mg;

The shell composition:

shellac 37% in terms of dry matter – 3.0 mg, sucrose – 92.399 mg, calcium carbonate – 91.675 mg, talc – 55.130 mg, acacia gum – 14.144 mg, corn starch – 10.230 mg, titanium dioxide (E 171) – 14.362 mg, colloidal silica – 6.138 mg, povidone (K=30 value) – 7.865 mg, macroGol-6000 – 2.023 mg, glycerol 85% in terms of dry matter – 2.865 mg, polysorbate 80 – 0.169 mg, mountain glycol wax – 0.120 mg.

How to take, the dosage

Ingestion.

The tablet should be taken with plenty of fluids.

Unless otherwise directed by the physician, an adult patient should take 1 tablet daily. In acute cases, the dose may be increased to 1 tablet 3 times a day after consulting a physician.

After 4 weeks of treatment, the physician should decide whether to continue taking the drug in an increased dose and consider reducing the increased dose of vitamins B6 and B1 to 1 tablet per day. If possible, the dose should be reduced to 1 tablet daily to reduce the risk of vitamin B6-associated neuropathy.

Interaction

In therapeutic doses, pyridoxine (vitamin B6) may reduce the effect of levodopa. Concomitant use of pyridoxine antagonists (e.g., hydralazine, isoniazid, penicillamine, cycloserine), alcohol consumption and long-term use of estrogen-containing oral contraceptives may lead to vitamin B6 deficiency in the body.

When taken concomitantly with fluorouracil there is deactivation of thiamine (vitamin B1) because fluorouracil competitively inhibits phosphorylation of thiamine to thiamine diphosphate.

Special Instructions

When using the drug at a dose of 100 mg daily for more than 6 months, development of sensory peripheral neuropathy is possible.

Potential effect on reaction rate when driving motor transport or operating other mechanisms. There are no precautions concerning the use of the drug by drivers of vehicles and persons working with potentially dangerous mechanisms.

Contraindications

Pregnancy and breast-feeding period. (See section “Use in pregnancy and during breastfeeding”).

Children’s age due to lack of data.

Each tablet contains 92.4 mg of sucrose. Therefore, the drug should not be used in persons with congenital fructose intolerance, glucose and galactose malabsorption syndrome or glucose isomaltase deficiency.

If you have any of the above conditions, be sure to talk to your doctor before taking this medicine.

Overdose

Symptoms of overdose.

Given the wide therapeutic range, an overdose of benfotiamine when taken orally is unlikely.

High doses of pyridoxine (vitamin B6) taken for a short time (at a dose of more than 1 g per day) may lead to transient neurotoxic effects. When using the drug in a dose of 100 mg per day for more than 6 months it is also possible to develop neuropathies.

Overdose usually manifests as the development of sensory polyneuropathy, which may be accompanied by ataxia. Administration of the drug in extremely high doses may lead to convulsions. On newborns and infants the drug may have a strong sedative effect, cause hypotension and respiratory disorders (dyspnea, apnea).

The treatment of overdose.

If pyridoxine is taken in a dose greater than 150 mg/kg body weight, it is recommended to induce vomiting and take activated charcoal. Provocation of vomiting is most effective within the first 30 minutes of taking the drug. Emergency measures may need to be taken.