Combilipen^® Neuro tabs (Tablets) Instructions for Use

Marketing Authorization Holder

Pharmstandard-UfaVITA OJSC (Russia)

ATC Code

A11DB (Vitamin B1 in combination with vitamins B6 and/or B12)

Active Substances

Benfotiamine (Rec.INN registered by WHO)

Pyridoxine (Rec.INN registered by WHO)

Dosage Form

Combilipen® Neuro tabs

Film-coated tablets 100 mg+100 mg: 15, 30, 45 or 60 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex; the core on the cross-section is white or almost white.

Excipients (core) microcrystalline cellulose 200 – 225.5 mg, povidone (medium molecular weight polyvinylpyrrolidone, povidone K-30) – 8 mg, colloidal silicon dioxide – 6.75 mg, sodium lauryl sulfate – 4.5 mg, croscarmellose sodium – 3 mg, calcium stearate – 2.25 mg.

Excipients (shell) Opadry II white 57M280000 – 13.5 mg [hypromellose (hydroxypropyl methylcellulose) – 4.185 mg, titanium dioxide – 3.645 mg, polydextrose – 3.51 mg, talc – 0.945 mg, dextrin (maltodextrin) – 0.675 mg, glycerol (glycerin) – 0.54 mg].

15 pcs. – contour cell packaging (1) – cardboard packs.
15 pcs. – contour cell packaging (2) – cardboard packs.
15 pcs. – contour cell packaging (3) – cardboard packs.
15 pcs. – contour cell packaging (4) – cardboard packs.

Clinical-Pharmacological Group

B complex vitamins

Pharmacotherapeutic Group

B vitamins

Pharmacological Action

A combined medicinal product containing B vitamins.

Benfotiamine, 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-oxoglutarate 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 affecting all stages of the non-oxidative metabolism of amino acids.

Pyridoxal phosphate participates in the process of amino acid decarboxylation, and, consequently, in the formation of physiologically active amines (e.g., epinephrine, serotonin, dopamine, tyramine).

By participating in the transamination of amino acids, pyridoxal phosphate is involved in anabolic and catabolic processes (e.g., being a coenzyme of transaminases such as glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, GABA, α-ketoglutarate transaminase), as well as in various reactions of amino acid breakdown and synthesis.

Vitamin B₆ is involved in 4 different stages of tryptophan metabolism.

Pharmacokinetics

When taken orally, most of the benfotiamine is absorbed in the duodenum, a smaller part – in the upper and middle sections of the small intestine.

Benfotiamine is absorbed by active resorption at concentrations ≤2 µmol and by passive diffusion at concentrations ≥2 µmol.

Being a fat-soluble derivative of thiamine (vitamin B₁), Benfotiamine is absorbed faster and more completely than the 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, has high penetrating ability and is absorbed mainly without converting to thiamine.

Due to enzymatic debenzoylation after absorption, thiamine and the biologically active coenzymes thiamine diphosphate and thiamine triphosphate are formed.

Particularly 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 through passive diffusion.

In blood serum, pyridoxal phosphate and pyridoxal are bound to 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 remaining part consists of several metabolites, among which thiamine acid, methylthiazole-acetic acid, and pyramine are distinguished.

The average T_1/2 of benfotiamine from the blood is 3.6 hours.

The T_1/2 of pyridoxine when taken orally is approximately 2-5 hours.

The biological T_1/2 of thiamine and pyridoxine is approximately 2 weeks.

Indications

Neurological diseases with confirmed deficiency of vitamins B₁ and B₆.

ICD codes

Dosage Regimen

Take orally 1-3 times/day, depending on the indications.

After 4 weeks of treatment, the doctor should decide on the need to continue taking this medicinal product at an increased dose and consider the possibility of reducing the dose of vitamins B₆ and B₁ to 1 single dose/day.

If possible, the dose should be reduced to 1 single dose/day in order to reduce the risk of developing neuropathy associated with the use of vitamin B₆.

Adverse Reactions

Allergic reactions: very rarely – skin reactions, itching, urticaria, skin rash, difficulty breathing, angioedema, anaphylactic shock.

From the nervous system in some cases – headache; frequency unknown (isolated spontaneous reports) – peripheral sensory neuropathy with long-term use of the drug (more than 6 months).

From the digestive system: very rarely – nausea.

From the skin and subcutaneous tissue: frequency unknown (isolated spontaneous reports) – acne, increased sweating.

From the cardiovascular system: frequency unknown (isolated spontaneous reports) – tachycardia.

Contraindications

Decompensated heart failure; childhood; pregnancy; breastfeeding period; hypersensitivity to thiamine, benfotiamine, pyridoxine.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Pediatric Use

Contraindicated in childhood (due to lack of data).

Special Precautions

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

Drug Interactions

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 simultaneously with fluorouracil, deactivation of thiamine (vitamin B₁) is noted, since fluorouracil competitively inhibits the phosphorylation of thiamine to thiamine diphosphate.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.