Milgamma compositum tablets p / o, No. 60

Neurological diseases with a confirmed deficiency of vitamins B1 and B6.

Inside.

The tablet should be taken with plenty of liquid.

Unless otherwise prescribed by the attending physician, an adult patient should take 1 tablet per day.

In acute cases, after consulting a doctor, the dose may be increased to 1 tablet 3 times a day.

After 4 weeks of treatment, the doctor 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 per day in order to reduce the risk of developing neuropathy associated with the use of vitamin B6.

1 coated tablet contains:

Active ingredients: benfotiamine 100 mg, pyridoxine hydrochloride 100 mg.

Excipients:

composition of the coated tablet core: microcrystalline cellulose - 222.0 mg, povidone (K value = 30) - 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;

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 silicon dioxide - 6.138 mg, povidone (K value = 30) - 7.865 mg, macrogol-6000 - 2.023 mg, glycerol 85% in terms of dry matter - 2.865 mg, polysorbate-80 - 0.169 mg, wax mountain glycolic - 0.120 mg

• Increased individual sensitivity to thiamine, benfotiamine, pyridoxine or other components of the drug.

• The period of pregnancy and breastfeeding. (See section 'Use during pregnancy and breastfeeding').

• Children's age due to lack of data.

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

If you have one of the listed diseases, be sure to consult your doctor before taking the drug.

Pharmacodynamics:

Benfotiamine, a fat-soluble derivative of thiamine (vitamin B1), is phosphorylated in the body to 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) - pyridoxal phosphate - is a coenzyme of a number of 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 (for example, adrenaline, serotonin, dopamine, tyramine). Taking part in the transamination of amino acids, pyridoxal phosphate is involved in anabolic and catabolic processes (for example,being a coenzyme of such transaminases as glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, gamma aminobutyric acid (GABA), ?-ketoglutarate transaminase), as well as in various reactions of decomposition and synthesis of amino acids. Vitamin B6 is involved in 4 different steps in tryptophan metabolism.

Pharmacokinetics:

When taken orally, most of benfotiamine is absorbed in the duodenum, less in the upper and middle parts of the small intestine. Benfotiamine is absorbed through active resorption at concentrations of 2 ?mol and through passive diffusion at concentrations of 2 ?mol.

Being a fat-soluble derivative of thiamine (vitamin B1), benfotiamine is absorbed faster and more completely than water-soluble thiamine hydrochloride. In the intestine, benfotiamine is converted to S-benzoylthiamine as a result of dephosphorylation by phosphatases. S-benzoylthiamine is fat-soluble, highly penetrating and absorbed mainly without being converted to thiamine. Due to enzymatic debenzoylation after absorption, thiamine and biologically active coenzymes of 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 mainly in the upper gastrointestinal tract during passive diffusion. In blood serum, pyridoxal phosphate and pyridoxal are associated with albumin.

Before penetrating the cell membrane, pyridoxal phosphate bound to albumin is hydrolyzed by alkaline phosphatase to form pyridoxal. Both vitamins are excreted mainly in the urine. Approximately 50% of thiamine is excreted unchanged or as sulfate. The rest is made up of several metabolites, among which thiamic acid, methylthiazo-acetic acid and pyramine are distinguished. The average half-life of benfotiamine from the blood is 3.6 hours. 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.

Side effect:

The frequency of side effects is distributed in the following order: very often (more than 10% of cases), often (in 1% - 10% of cases), infrequently (in 0.1% - 1% of cases), rarely (in 0.01% - 0 , 1% of cases), very rarely (less than 0.01% of cases), as well as side effects, which are often unknown. Immune system disorders: Very rarely: hypersensitivity reaction (skin reactions, itching, urticaria, skin rash, shortness of breath, Quincke's edema, anaphylactic shock). In some cases, headache. From the nervous system: The frequency is not known (isolated spontaneous messages): peripheral sensory neuropathy with prolonged use of the drug (more than 6 months). From the gastrointestinal tract: Very rare: nausea. On the part of the skin and subcutaneous fat: The frequency is not known (isolated spontaneous messages): acne, increased sweating.From the side of the cardiovascular system: The frequency is not known (isolated spontaneous messages): tachycardia. Х If any of the side effects indicated in the instructions are aggravated, or you notice any other side effects not listed in the instructions, inform your doctor.

Overdose:

Overdose symptoms. Given the wide therapeutic range, an overdose of oral benfotiamine is unlikely. Taking high doses of pyridoxine (vitamin B6) for a short period of time (at a dose of more than 1 g per day) can lead to short-term neurotoxic effects. When using the drug at a dose of 100 mg per day for more than 6 months, the development of neuropathies is also possible. Overdose, as a rule, manifests itself in the form of the development of sensory polyneuropathy, which may be accompanied by ataxia. Taking the drug in extremely high doses can lead to convulsions. On newborns and infants, the drug can have a strong sedative effect, cause hypotension and breathing disorders (dyspnea, apnea).

Overdose treatment. When taking pyridoxine at a dose exceeding 150 mg / kg body weight, it is recommended to induce vomiting and take activated charcoal. Vomiting is most effective within the first 30 minutes after taking the drug. Urgent action may be required.

Interaction with other medicinal products:

At therapeutic doses, pyridoxine (vitamin B6) can reduce the effect of levodopa. The simultaneous use of pyridoxine antagonists (for example, hydralazine, isoniazid, penicillamine, cycloserine), alcohol consumption and prolonged use of estrogen-containing oral contraceptives can lead to vitamin B6 deficiency in the body. When taken simultaneously with fluorouracil, deactivation of thiamine (vitamin B1) is noted, since fluorouracil competitively suppresses the phosphorylation of thiamine to thiamine diphosphate.

Special instructions:

When using the drug at a dose of 100 mg per day for more than 6 months, the development of sensory peripheral neuropathy is possible. The ability to influence the reaction rate when driving or using other mechanisms. There are no warnings regarding the use of the drug by vehicle drivers and persons working with potentially dangerous machinery.