Combilipen, 2 ml 5 pcs

Pharmacotherapeutic group:B vitamins + other drugs

ATX code: A11DB/N07X

Pharmacological properties

.Pharmacodynamics

A combined multivitamin drug. The action of the drug is determined by the properties of the vitamins in its composition. Neurotropic B vitamins have a favorable effect on inflammatory and degenerative diseases of the nervous system and the musculoskeletal system.

Tiamine (vitamin B ₁) – plays a key role in the processes of carbohydrate metabolism, which is critical in the metabolic processes of nervous tissue (involved in the conduct of the nerve impulse) and the Krebs cycle with subsequent participation in the synthesis of thiamine pyrophosphate (TPP) and adenosine triphosphate (ATP).

Pyridoxine (vitamin B₆) – has a vital effect on the metabolism of proteins, carbohydrates and fats, is essential for normal hematopoiesis and the functioning of the central and peripheral nervous system. It provides synaptic transmission, the processes of inhibition in the central nervous system (CNS), participates in the transport of sphingosine, which is part of the nerve sheath, participates in the synthesis of catecholamines.

The physiological function of both vitamins (B₁ and B₆) is to potentiate each other’s action, manifesting as a positive effect on the nervous, neuromuscular and cardiovascular systems.

Cyanocobalamin (vitamin B₁₂) – is involved in the synthesis of nucleotides, is an important factor for normal growth, hematopoiesis and development of epithelial cells; it is necessary for the metabolism of folic acid and the synthesis of myelin.

Lidocaine has anesthetic effect at the injection site, dilates blood vessels and promotes the absorption of vitamins. The local anesthetic effect of lidocaine is due to the blockade of potential-dependent sodium channels, which prevents generation of impulses in the endings of sensitive nerves and conduct of pain impulses along the nerve fibers.

Pharmacokinetics

Thiamine

.After intramuscular administration, thiamine is rapidly absorbed from the injection site and enters the blood (484 ng/mL after 15 minutes on the first day of a 50 mg dose) and is unevenly distributed in the body with a leukocyte content of 15%, erythrocyte content of 75%, and plasma content of 10%. Because of the lack of significant stores of the vitamin in the body, it must be supplied daily. Thiamine penetrates through the blood-brain barrier and placental barrier and is found in breast milk. Thiamine is excreted by the kidneys in the alpha phase after 0.15 hours, in the beta phase – after 1 hour, in the final (terminal) phase – within 2 days. The main metabolites are: thiaminicarboxylic acid, pyramine and some unknown metabolites. Of all vitamins, thiamine is retained in the body in the smallest amounts. The adult body contains about 30 mg of thiamine: 80% as thiamine pyrophosphate, 10% as thiamine triphosphate and the rest as thiamine monophosphate.

Pyridoxine

.After intramuscular injection, pyridoxine is rapidly absorbed from the injection site and distributed in the body, acting as a coenzyme after phosphorylation of the CH₂OH group in the 5th position. About 80% of the vitamin is bound to plasma proteins. Pyridoxine is distributed throughout the body, passes through the placenta, is found in breast milk. It accumulates in the liver and is oxidized to 4-pyridoxic acid, which is excreted by the kidneys a maximum of 2-5 hours after absorption.

The human body contains 40-150 mg of vitamin B₆ and its daily elimination rate is about 1.7-3.6 mg with a 2.2-2.4% supplementation rate.

Cyanocobalamin

Cyanocobalamin binds to transcobalamin I and II after intramuscular administration and is transported to various body tissues. Maximum concentration after intramuscular administration is reached after 1 hour. Binding with blood plasma proteins is 90%. It penetrates through the placental barrier and is detected in breast milk. It is metabolized mainly in the liver to form adenosylcobalamin, which is the active form of cyanocobalamin. It is deposited in the liver, passes into the intestine with the bile and is absorbed back into the blood (enterohepatic recirculation phenomenon). The half-life is long, it is excreted mainly by the kidneys (7-10%) and through the intestines (50%). With decreased renal function, excretion by the kidneys is 0-7 % and through the intestine 70-100 %.

Lidocaine

In intramuscular administration, the maximum plasma concentration of lidocaine is observed 5-15 minutes after injection. Depending on the dose, about 60-80% of lidocaine is bound to plasma proteins. It is rapidly distributed (within 6-9 minutes) in organs and tissues with good perfusion, including heart, lung, liver, kidney and then in muscle and fat tissue. It penetrates through the blood-brain barrier and the placental barrier, is found in breast milk (up to 40% of the concentration in maternal plasma). It is metabolized in the liver with the participation of microsomal enzymes to form active metabolites – monoethylglycinxylide and glycinxylide, which have half-life of 2 and 10 hours, respectively. The intensity of metabolism is reduced in liver disease. It is excreted mainly as metabolites by kidneys and up to 10% unchanged.

Indications

In complex therapy:
– mono- and polyneuropathies of various genesis;
– dorsalgia;
– plexopathies;
– lumboichyalgia;
– radicular syndrome caused by degenerative changes in the spine.

Composition

Actives:
Tiamine hydrochloride – 100 mg
Pyridoxine hydrochloride – 100 mg
Cyanocobalamin – 1 mg
Lidocaine hydrochloride – 20 mg
Associates: benzyl alcohol – 40.0 mg, sodium tripolyphosphate – 20.0 mg, potassium hexacyanoferrate – 0.20 mg, sodium hydroxide – to pH 4.5 ± 0.2, water for injection – to 2 ml.

How to take, the dosage

Injections are performed deeply intramuscularly (see section “Special indications”).
In cases of severe pain syndrome it is reasonable to begin treatment with intramuscular injection (deep) of 2 ml daily during 5-10 days with further change to oral intake, or to less frequent injections (2-3 times a week during 2-3 weeks) with possible continuation of therapy by oral dosage form.
Needs weekly monitoring of therapy by a physician. The duration of treatment is determined by the doctor individually, depending on the severity of symptoms.
The transition to therapy with oral dosage form is recommended to be carried out as soon as possible.

Interaction

B vitamins

Vitamin B1 (thiamine) breaks down completely in solutions containing sulfites. And as a consequence, the breakdown products of thiamine inactivate the actions of other vitamins. Thiamine is incompatible with oxidizing and reducing compounds, including: mercury chloride, iodide, carbonate, acetate, tannic acid, iron-ammonium citrate, as well as phenobarbital, riboflavin, benzylpenicillin, dextrose and metabisulfite. Copper accelerates thiamine degradation; also, thiamine loses its effectiveness with increasing pH values (more than 3).

Therapeutic doses of vitamin B6 (pyridoxine) weaken the effect of levodopa (decrease the anti-Parkinsonian effect of levodopa) when used simultaneously. Interaction with cycloserine, penicillamine, isoniazid is also observed.
Vitamin B12 (cyanocobalamin) is incompatible with ascorbic acid and salts of heavy metals.

Lidocaine
Parenteral use of lidocaine, in case of additional use of norepinephrine and epinephrine, increased adverse reactions on the heart may occur. Interaction with sulfonamides is also observed. In case of overdose of local anesthetic agents, epinephrine and norepinephrine should not be used additionally.

Special Instructions

The drug should only be injected intramuscularly, avoiding vascular ingestion. In case of accidental intravenous administration, the patient should be under medical supervision or hospitalized depending on the severity of symptoms.

The drug may cause neuropathies if the duration of use exceeds 6 months.

Influence on driving and operating ability

There is no information about the effect of the drug on driving ability as well as on performance of potentially dangerous activities requiring increased concentration and rapid psychomotor reactions. However, caution is recommended, taking into account the possibility of developing adverse reactions of the drug.

Synopsis

Contraindications

High sensitivity to components of the drug.

Acute heart failure, decompensated chronic heart failure.

Children under 18 years of age (efficacy and safety not established).

Pregnancy and breastfeeding.

Overdose

Symptoms: vomiting, bradycardia, arrhythmia, possible systemic reactions including dizziness, confusion, seizures.

Treatment: In case of symptoms of overdose, treatment with the drug should be withdrawn, with symptomatic therapy if necessary.

Pregnancy use