Celular

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CELULAR (CELULAR)

Composition:

Active substances: thiamine hydrochloride, pyridoxine hydrochloride, cyanocobalamin;

1 ml of solution contains thiamine hydrochloride (calculated as 100 % substance) 50 mg, pyridoxine hydrochloride (calculated as 100 % substance) 50 mg, cyanocobalamin (calculated as 100 % substance) 0.5 mg;

Excipients: lidocaine hydrochloride, benzyl alcohol, sodium polyphosphate, potassium ferricyanide, sodium hydroxide, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical characteristics: clear red-colored liquid.

Pharmacotherapeutic group. Vitamin B1 preparations in combination with vitamin B6 and/or vitamin B12. ATC code A11DB.

Pharmacological Properties

Pharmacodynamics

Neurotropic vitamins of the B group exert beneficial effects in inflammatory and degenerative diseases of the nerves and musculoskeletal system. They should be used to correct deficiency states; in high doses, they possess analgesic properties, improve blood circulation, and help normalize nervous system function and hematopoiesis.

Vitamin B1 is a highly important active substance. In the body, vitamin B1 is phosphorylated to form the biologically active compounds thiamine diphosphate (cocarboxylase) and thiamine triphosphate (TTP).

Thiamine diphosphate acts as a coenzyme in key carbohydrate metabolism processes, which are crucial for metabolic functions in nervous tissue and influence nerve impulse transmission in synapses. In vitamin B1 deficiency, metabolites accumulate in tissues—primarily lactic and pyruvic acids—leading to various pathological conditions and disturbances in nervous system function.

Vitamin B6 in its phosphorylated form (pyridoxal-5’-phosphate, PLP) serves as a coenzyme for several enzymes involved in general non-oxidative amino acid metabolism. Through decarboxylation, it participates in the formation of physiologically active amines (e.g., adrenaline, histamine, serotonin, dopamine, tyramine); through transamination, it contributes to anabolic and catabolic metabolic processes (e.g., glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, γ-aminobutyric acid, α-ketoglutarate transaminase), as well as various amino acid synthesis and degradation pathways. Vitamin B6 acts at four different stages of tryptophan metabolism. In hemoglobin synthesis, vitamin B6 catalyzes the formation of δ-aminolevulinic acid.

Vitamin B12 is essential for cellular metabolic processes. It influences hematopoietic function (as the extrinsic anti-anemic factor), participates in the formation of choline, methionine, creatinine, and nucleic acids, and exerts analgesic effects.

Pharmacokinetics

After parenteral administration, thiamine is distributed throughout the body. Approximately 1 mg of thiamine is metabolized daily. Metabolites are excreted in urine. Dephosphorylation occurs in the kidneys. The biological half-life of thiamine is 0.35 hours. Thiamine does not accumulate in the body due to its limited lipid solubility.

Vitamin B6 is phosphorylated and oxidized to pyridoxal-5-phosphate. In blood plasma, pyridoxal-5-phosphate and pyridoxal are bound to albumin. Pyridoxal is the transport form. To cross the cell membrane, albumin-bound pyridoxal-5-phosphate is hydrolyzed by alkaline phosphatase to pyridoxal.

After parenteral administration, vitamin B12 forms transport protein complexes that are rapidly absorbed by the liver, bone marrow, and other proliferative tissues. Vitamin B12 is excreted into bile and participates in enterohepatic circulation. Vitamin B12 crosses the placenta.

Clinical characteristics.

Indications.

Systemic neurological disorders caused by a confirmed deficiency of vitamins B1, B6, and B12, when they cannot be corrected by dietary intake.

Contraindications.

Hypersensitivity to the components of the medicinal product; acute impairment of cardiac conduction; acute phase of decompensated heart failure.

Vitamin B1 — contraindicated in allergic reactions.

Vitamin B6 — contraindicated in peptic ulcer of the stomach and duodenum in the stage of exacerbation (due to possible increase in gastric juice acidity).

Vitamin B12 — contraindicated in erythremia, erythrocytosis, thromboembolism.

Lidocaine. Increased individual sensitivity to lidocaine or to other amide-type local anesthetics, history of epileptiform seizures induced by lidocaine, severe bradycardia, severe arterial hypotension, cardiogenic shock, severe forms of chronic heart failure (Grade II–III), sick sinus syndrome, Wolff–Parkinson–White syndrome, Adams–Stokes syndrome, second- and third-degree atrioventricular block, hypovolemia, severe impairment of liver/kidney function, porphyria, myasthenia.

Pregnancy and breastfeeding period.

Interaction with other medicinal products and other types of interactions.

Thiamine is completely degraded by sulfite-containing solutions. Other vitamins may be inactivated in the presence of vitamin B1 degradation products. Therapeutic doses of vitamin B6 may reduce the effect of L-dopa. Other interactions occur with isoniazid, D-penicillamine, and cycloserine.

When lidocaine is administered parenterally, cardiac adverse effects may be potentiated by the use of adrenaline or noradrenaline. Other interactions exist with sulfonamides.

In case of overdose of local anesthetics, adrenaline and noradrenaline must not be used.

Special precautions for use

The medicinal product contains lidocaine hydrochloride and therefore should be administered only by intramuscular injection. Intravenous (i.v.) administration into the bloodstream is not permitted. In case of accidental intravenous injection, medical monitoring or hospital observation may be required depending on the severity of symptoms. Prolonged use of the medicinal product for more than 6 months may lead to reversible peripheral sensory neuropathy.

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e. it is practically sodium-free.

This medicinal product contains less than 1 mmol (39 mg)/dose of potassium, i.e. it is practically potassium-free.

This medicinal product contains benzyl alcohol. Benzyl alcohol has been associated with serious adverse reactions („gasping syndrome“) in neonates and young children.

Due to the risk of accumulation and toxicity (metabolic acidosis), large amounts of benzyl alcohol should be used only with caution and only when absolutely necessary, particularly in patients with impaired liver or kidney function, as well as during pregnancy and breastfeeding.

Use during pregnancy or breastfeeding

During pregnancy, the recommended daily intake of vitamin B1 is 1.2 mg in the 2nd trimester and 1.3 mg in the 3rd trimester, and of vitamin B6 is 1.9 mg from the 4th month of pregnancy. This medicinal product should be used during pregnancy only if a deficiency in vitamins B1 and B6 has been confirmed, as the safety of doses exceeding the recommended daily intake has not yet been established.

During breastfeeding, the recommended daily intake of vitamin B1 is 1.3 mg and of vitamin B6 is 1.9 mg.

Vitamins B1 and B6 are excreted into breast milk. High doses of vitamin B6 may reduce milk production.

The medicinal product contains 100 mg of vitamin B6 per ampoule; therefore, it should not be used during pregnancy or breastfeeding.

The potential use of this medicinal product during pregnancy and breastfeeding should be considered by a physician only after a thorough risk/benefit assessment.

Effect on ability to drive and use machines
The medicinal product does not affect the ability to drive or operate complex machinery.

Method of Administration and Dosage

In severe (acute) cases, treatment should be initiated with 2 mL of the solution administered intramuscularly once daily until acute symptoms subside. For continuation of therapy, administer 2 mL (1 injection) 2–3 times per week.

Weekly medical monitoring is recommended throughout the course of treatment.

Every effort should be made to switch to oral therapy as early as possible.

Intramuscular (i.m.) administration only is permitted. Intravenous (i.v.) administration into the circulatory system is not allowed. In case of accidental intravenous injection, depending on the severity of symptoms, medical monitoring or hospital observation is required.

For maintenance or continuation of the therapeutic course of injections, or for prevention of relapse, oral medications of a similar pharmacotherapeutic group are recommended.

Children. The medicinal product must not be used in children.

Overdose

Vitamin B1 has a wide therapeutic range. Very high doses (over 10 g) may produce curare-like effects, suppressing nerve impulse conduction.

Vitamin B6 has very low toxicity.

Excessive use of vitamin B6 at doses exceeding 1 g per day over several months may lead to neurotoxic effects. Neuropathies with ataxia and sensory disturbances, cerebral convulsions with EEG changes, and in isolated cases hypochromic anemia and seborrheic dermatitis have been reported after administration of more than 2 g per day.

Vitamin B12: following parenteral administration (rarely also after oral use), doses higher than recommended have been associated with allergic reactions, eczematous skin disorders, and benign forms of acne.

Prolonged use in high doses may lead to impaired liver enzyme activity, chest pain, and hypercoagulability.

Treatment: symptomatic therapy.

Lidocaine. Symptoms: psychomotor excitation, dizziness, general weakness, decreased arterial blood pressure, tremor, visual disturbances, tonic-clonic seizures, coma, collapse, possible atrioventricular block, central nervous system depression, and respiratory arrest. Initial symptoms of overdose in healthy individuals occur at blood lidocaine concentrations exceeding 0.006 mg/kg; seizures occur at 0.01 mg/kg.

Treatment: discontinue drug administration, oxygen therapy, anticonvulsants, vasoconstrictors (noradrenaline, mesaton), and in case of bradycardia—anticholinergics (0.5–1 mg atropine). Endotracheal intubation, artificial ventilation of the lungs, and resuscitation measures may be necessary. Dialysis is ineffective.

Adverse Reactions

The following frequency terms are used to classify adverse reactions: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), and not known (frequency cannot be estimated from available data).

Immune system disorders: not known — benzyl alcohol may cause allergic reactions; very rare — hypersensitivity reactions (e.g., exanthema, dyspnea, shock, angioedema).

Skin and subcutaneous tissue disorders: very rare — hyperhidrosis, acne, pruritic skin reactions, urticaria.

Cardiac disorders: very rare — tachycardia.

General disorders and administration site conditions: not known — systemic reactions due to rapid accumulation (e.g., accidental intravenous injection, injection into highly vascularized tissue) or overdose. Dizziness, vomiting, bradycardia, cardiac arrhythmias, seizures. Burning sensation at the injection site.

Reporting of adverse reactions after drug registration is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. Keep out of reach and sight of children. Store in the original packaging at a temperature of 2 °C to 8 °C.

Incompatibilities.

Thiamine is incompatible with oxidizing and reducing agents: mercury chloride, iodides, carbonates, acetates, tannic acid, iron-ammonium citrate, as well as with sodium phenobarbital, riboflavin, benzylpenicillin, glucose, and metabisulfite, as it becomes inactivated in their presence. Copper accelerates thiamine degradation; additionally, thiamine loses its activity at increased pH values (above 3).

Vitamin B12 is incompatible with oxidizing and reducing agents and heavy metal salts.

In solutions containing thiamine, vitamin B12, like other B-complex vitamins, is rapidly degraded by thiamine breakdown products (low concentrations of iron ions may offer protection). Riboflavin, particularly under exposure to light, also causes degradation; nicotinamide accelerates photolysis, whereas antioxidants exert an inhibitory effect.

Packaging. 2 ml in a vial; 5 vials per blister, 1 blister per carton.

Prescription status. Prescription only.

Manufacturer. Private Joint-Stock Company "Lekhim-Kharkiv".

Manufacturer's address and site of operations.
36 Severin Pototskoho Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.