Combilipen, 2 ml 10 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.

Thiamine (vitamin B ₁) – plays a key role in the processes of carbohydrate metabolism, which are 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 myelin synthesis.

Lidocaine has an 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 the generation of impulses in the endings of sensitive nerves and the conduct of pain impulses along the nerve fibers.

Pharmacokinetics

Tiamine

. 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 the 50 mg dose) and is unevenly distributed in the body, with its content in leukocytes 15%, red blood cells 75% and plasma 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-pyridoxylic acid, which is excreted by the kidneys in maximum 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 replenishment rate of 2.2-2.4%.

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 it is eliminated by the kidneys (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

Neck pain, trigeminal neuralgia, Neuritis, Sciatica, Neuralgia, Back pain, Pain, Lumbago

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

Composition

Active ingredients:
Thiamine hydrochloride – 100 mg
Pyridoxine hydrochloride – 100 mg
Cyanocobalamin – 1 mg
Lidocaine hydrochloride – 20 mg
Excipients: 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 start treatment with intramuscular injection (deep) of 2 ml daily for 5-10 days with further transition either to oral administration or to less frequent injections (2-3 times a week for 2-3 weeks) with possible continuation of therapy with oral dosage form.

Therapies need to be monitored weekly by a physician. The duration of therapy is determined by the doctor individually, depending on the severity of the symptoms.

The transition to therapy with oral dosage form is recommended 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 the degradation of thiamine; in addition, thiamine loses its effectiveness when the pH is increased (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
In parenteral use of lidocaine, in case of additional use of norepinephrine and epinephrine, an increase in adverse reactions on the heart is possible. 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 administered intramuscularly, avoiding vascular ingestion. If accidentally administered intravenously, the patient should be monitored by a physician or hospitalized, depending on the severity of symptoms.

The drug may cause neuropathies if used for more than 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 quick psychomotor reactions. However, caution is recommended, taking into account the possibility of development of undesirable reactions of the drug.

Synopsis

Transparent pinkish-red liquid with a peculiar odor.

Contraindications

Hypersensitivity to the components of the drug.

Acute heart failure, chronic heart failure in the stage of decompensation.

Children under 18 years of age (effectiveness and safety have not been established).

The period of pregnancy and breastfeeding.

Overdose

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

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

Pregnancy use

The use of the drug is contraindicated during pregnancy and breastfeeding.