Vitacetin

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT VITACERTIN (VITACERTIN)

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 ferrocyanide, sodium hydroxide, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: 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 B-group vitamins exert beneficial effects on inflammatory and degenerative disorders of nerves and the musculoskeletal system. They are used to correct deficiency states, and in high doses demonstrate analgesic properties, improve blood circulation, normalize nervous system function, and support hematopoiesis.

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

Thiamine diphosphate acts as a coenzyme involved in key carbohydrate metabolism processes, which are crucial for metabolic activities in nervous tissue and influence nerve impulse transmission in synapses. In vitamin B1 deficiency, metabolites accumulate in tissues, primarily lactic acid and pyruvic acid, 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, these enzymes contribute to the formation of physiologically active amines (epinephrine, histamine, serotonin, dopamine, tyramine), and via transamination, to anabolic and catabolic metabolic processes (e.g., glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, γ-aminobutyric acid, α-ketoglutarate transaminase), as well as to 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 α-amino-β-keto-adipic acid.

Vitamin B12 is essential for cellular metabolic processes. It influences hematopoietic function (as an 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 21 minutes. Thiamine does not accumulate in the body due to its limited solubility in lipids.

Vitamin B6 is phosphorylated and oxidized to pyridoxal-5'-phosphate. In blood plasma, pyridoxal-5'-phosphate and pyridoxal are bound to albumin. The transported form is pyridoxal. To cross the cell membrane, pyridoxal-5'-phosphate bound to albumin is hydrolyzed by alkaline phosphatase into 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 is contraindicated in allergic reactions.

Vitamin B6 is contraindicated in peptic ulcer disease of the stomach and duodenum during exacerbation (possible increase in gastric juice acidity).

Vitamin B12 is contraindicated in erythremia, erythrocytosis, and thromboembolism.

• Lidocaine.* Increased individual sensitivity to lidocaine or to other amide-type local anesthetics, history of epileptiform seizures in response to lidocaine, severe bradycardia, severe arterial hypotension, cardiogenic shock, severe forms of chronic heart failure (grades II–III), sick sinus syndrome, Wolff–Parkinson–White syndrome, Adams–Stokes syndrome, second- and third-degree atrioventricular block (AV block), hypovolemia, severe hepatic/renal dysfunction, porphyria, myasthenia gravis.

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 degradation products of vitamin B1. Therapeutic doses of vitamin B6 may reduce the effect of L-dopa. The medicinal product also interacts with isoniazid, D-penicillamine, and cycloserine.

When lidocaine is administered parenterally, cardiac adverse effects may be enhanced by concomitant use of adrenaline or noradrenaline. The medicinal product also interacts with sulfonamides.

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

Special precautions.

Vitacertin contains lidocaine hydrochloride; therefore, the medicinal product should be administered only intramuscularly. Intravenous (i.v.) administration into the bloodstream is not permitted. In case of accidental intravenous injection, depending on the severity of symptoms developed, medical supervision or hospital observation is required.

Prolonged use of vitamin B6 (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.

Vitacertin contains benzyl alcohol, which has been associated with a risk of serious adverse effects ("gasping syndrome") in newborns and young children. It should not be used in premature infants and newborns. It may cause toxic and allergic reactions in infants and children under 3 years of age. 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.

Use during pregnancy or breastfeeding.

The medicinal product should not be used during pregnancy or breastfeeding.

Ability to influence reaction rate when driving or operating machinery.

The medicinal product does not affect the ability to drive or operate complex machinery.

If dizziness occurs during treatment with this medicinal product, patients should refrain from driving and operating machinery.

Method of Administration and Dosage.

Dosage.

In severe and acute cases, to achieve a rapid increase in the drug level in the blood, treatment is initiated with 2 ml of the solution administered intramuscularly once daily. After the acute phase has subsided and in mild cases, 2 ml (1 injection) should be administered 2–3 times per week.

Weekly medical monitoring is recommended throughout the course of therapy.

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

Method of Administration.

Injections are administered deep into the muscle (intramuscularly).

Intramuscular injection should be performed into the upper outer quadrant of the gluteal muscle.

Warning to prevent inadvertent intravenous injection.

Vitacertin is intended for intramuscular (i.m.) use only. Intravenous (i.v.) administration into the bloodstream is not permitted. In case of accidental intravenous injection, medical monitoring or hospital observation is required depending on the severity of symptoms.

Children.

The medicinal product should not be used in children.

Overdose.

Overdose leads to an intensification of the drug's adverse effects.

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

Vitamin B6 has very low toxicity.

Excessive use of vitamin B6 in 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, as well as, 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, after oral use) of doses higher than recommended, allergic reactions, eczematous skin disorders, and benign forms of acne have been observed.

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

Treatment: symptomatic therapy.

Lidocaine. Symptoms: psychomotor agitation, dizziness, general weakness, decreased arterial pressure, tremor, visual disturbances, tonic-clonic seizures, coma, collapse, possible AV block, central nervous system depression, 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 (e.g., noradrenaline, mesaton), in case of bradycardia — anticholinergics (0.5–1 mg atropine). Intubation, artificial ventilation of the lungs, and resuscitation measures may be required. Dialysis is ineffective.

Adverse reactions

The frequency of adverse reactions is defined as follows:

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;
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: skin reactions with pruritus and urticaria, acneiform eruptions, sweating.

Cardiac disorders:
Very rare: tachycardia.

General disorders and administration site conditions:
Not known: systemic reactions due to rapid accumulation (accidental intravenous injection, injection into highly vascularized tissue) or overdose. Dizziness, vomiting, bradycardia, arrhythmia, seizures.

Burning sensation at the injection site.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after marketing authorization is of great importance. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Medical 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 the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

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

Incompatibilities

Thiamine is incompatible with oxidizing and reducing agents: mercuric 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; in addition, thiamine loses its activity at increased pH values (> 3).

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

In solutions containing thiamine, vitamin B12 and other B-complex vitamins are rapidly degraded by thiamine breakdown products (low concentrations of iron ions may provide protection). Riboflavin, particularly under light exposure, also exerts a destructive effect; nicotinamide accelerates photolysis, whereas antioxidants have an inhibitory effect.

Packaging. 2 ml in an ampoule, 5 ampoules in a blister pack, 1 blister pack in a carton.

Prescription status. Prescription only.

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

Manufacturer's address and location of operations.
36 Severina Pototskogo Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.