Vitaxon®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT VITAXON® (VITAXON)

Composition:

Active substances: thiamine hydrochloride, pyridoxine hydrochloride, cyanocobalamin;

1 ml of solution contains thiamine hydrochloride equivalent to 50 mg of 100% anhydrous substance, pyridoxine hydrochloride equivalent to 50 mg of 100% dry substance, cyanocobalamin equivalent to 0.5 mg of 100% dry substance;

Excipients: lidocaine hydrochloride, benzyl alcohol, sodium polyphosphate, potassium hexacyanoferrate(II), sodium hydroxide, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical characteristics: transparent red liquid with a specific odor.

Pharmacotherapeutic group. Vitamin B1 preparations in combination with vitamin B6 and/or vitamin B12. ATC code A11D B.

Pharmacological Properties

Pharmacodynamics

Neurotropic B vitamins have beneficial effects in inflammatory and degenerative diseases of nerves and the musculoskeletal system. They are used to correct deficiency states, and in high doses 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 biologically active thiamine diphosphate (coenzyme A, or cocarboxylase) and thiamine triphosphate (TTP).

Thiamine diphosphate acts as a coenzyme involved 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.

In its phosphorylated form (pyridoxal-5’-phosphate, PALP), vitamin B6 acts as a coenzyme for several enzymes involved in general non-oxidative amino acid metabolism. Through decarboxylation, these enzymes participate in the formation of physiologically active amines (epinephrine, histamine, serotonin, dopamine, tyramine); through transamination, they contribute 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 processes. Vitamin B6 is involved in four distinct 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 metabolism. It influences hematopoietic function (as an external anti-anemic factor), participates in the formation of choline, methionine, creatinine, and nucleic acids, and has analgesic properties.

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 bind to albumin. Pyridoxal is the transport form. 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.

Neurological disorders of various origins: neuritis, neuralgias, polyneuropathies (diabetic, alcoholic), radicular syndrome, retrobulbar neuritis, facial nerve lesions.

Contraindications.

Hypersensitivity to the components of the drug; acute impairment of cardiac conduction; acute decompensated heart failure.

Vitamin B1 – contraindicated in allergic reactions.

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

Vitamin B12 – contraindicated in erythremia, erythrocytosis, thromboembolism.

Lidocaine. Hypersensitivity 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 (stage II–III); sinus node dysfunction syndrome; Wolff-Parkinson-White syndrome; Adams-Stokes syndrome; second- and third-degree atrioventricular (AV) block; hypovolemia; severe hepatic or renal dysfunction; porphyria; myasthenia gravis.

Pregnancy or breastfeeding period.

Interaction with other medicinal products and other forms of interaction.

The action of thiamine is inactivated by 5-fluorouracil, as the latter competitively inhibits phosphorylation of thiamine to thiamine pyrophosphate. Loop diuretics, such as furosemide, which inhibit tubular reabsorption, may increase thiamine excretion during prolonged therapy and thus reduce thiamine levels.

Concomitant use with levodopa is contraindicated, as vitamin B6 may reduce the antiparkinsonian effect of levodopa. Concurrent use with pyridoxine antagonists (e.g., isoniazid, hydralazine, penicillamine, or cycloserine) or oral contraceptives may increase the requirement for vitamin B6.

Consumption of beverages containing sulfites (e.g., wine) increases thiamine degradation.

Lidocaine enhances the respiratory depressant effect of anesthetic agents (hexobarbital, intravenous sodium thiopental), hypnotics, and sedatives; reduces the cardiotonic effect of digoxin. Concomitant use with hypnotics and sedatives may enhance the central nervous system depressant effect. Ethanol enhances the respiratory depressant effect of lidocaine.

Adrenergic blockers (including propranolol, nadolol) – slow hepatic metabolism of lidocaine, enhance lidocaine effects (including toxic effects), and increase the risk of bradycardia and hypotension.

Curare-like agents – may deepen muscle relaxation (up to paralysis of respiratory muscles).

Norepinephrine, mexiletine – increase lidocaine toxicity (due to reduced lidocaine clearance).

Isadrine (isoprenaline) and glucagon – increase lidocaine clearance.

Cimetidine, midazolam – increase lidocaine plasma concentration. Cimetidine displaces lidocaine from protein binding and slows its hepatic inactivation, leading to an increased risk of enhanced adverse effects of lidocaine. Midazolam moderately increases lidocaine blood concentration.

Anticonvulsants, barbiturates (including phenobarbital) – may accelerate hepatic metabolism of lidocaine and reduce blood concentration.

Antiarrhythmic agents (amiodarone, verapamil, quinidine, ajmaline, disopyramide), anticonvulsants (hydantoin derivatives) – enhance cardiodepressive effects; concomitant use with amiodarone may lead to seizures.

Procaine, procainamide – combined use with lidocaine may cause central nervous system excitation and hallucinations.

Monoamine oxidase inhibitors, chlorpromazine, bupivacaine, amitriptyline, nortriptyline, imipramine – combined use with lidocaine increases the risk of arterial hypotension and prolongs the local anesthetic effect of lidocaine.

Narcotic analgesics (morphine, etc.) – combined use with lidocaine enhances the analgesic effect of narcotic analgesics, but also enhances respiratory depression.

Prenylamine – increases the risk of ventricular arrhythmia of the "torsade de pointes" type.

Propafenone – may increase the duration and severity of central nervous system-related adverse effects.

Rifampicin – may reduce lidocaine blood concentration.

Polymyxin B – respiratory function should be monitored.

Procainamide – may cause hallucinations.

Cardiac glycosides – combined use with lidocaine reduces the cardiotonic effect of cardiac glycosides.

Digitalis glycosides – in the setting of lidocaine intoxication, may exacerbate the severity of AV block.

Vasoconstrictors (epinephrine, methoxamine, phenylephrine) – combined use with lidocaine slows lidocaine absorption and prolongs its effect.

Guanadrel, guanethidine, mecamylamine, trimethaphan – combined use for spinal and epidural anesthesia increases the risk of pronounced hypotension and bradycardia.

β-adrenergic blockers – combined use slows hepatic metabolism of lidocaine, enhances lidocaine effects (including toxic effects), and increases the risk of bradycardia and arterial hypotension. When β-blockers and lidocaine are used concomitantly, the lidocaine dose should be reduced.

Acetazolamide, thiazide and loop diuretics – combined use with lidocaine reduces lidocaine efficacy due to hypokalemia.

Anticoagulants (including ardeparin, dalteparin, danaparoid, enoxaparin, heparin, warfarin, etc.) – combined use with lidocaine increases the risk of bleeding.

Anticonvulsants, barbiturates (phenytoin) – combined use with lidocaine may accelerate lidocaine metabolism in the liver, reduce blood concentration, and enhance cardiodepressive effects.

Agents causing neuromuscular blockade – combined use with lidocaine enhances the effect of neuromuscular blocking agents, as lidocaine reduces nerve impulse conduction.

Special precautions for use

The drug should not be administered intravenously. Intramuscular injections of vitamin B12 may cause anaphylactoid reactions in patients with increased sensitivity.

Parenteral administration of vitamin B12 may temporarily affect the diagnosis of funicular myelosis or pernicious anemia.

Prolonged use of vitamin B6: over 6–12 months at doses exceeding 50 mg daily, or over 1000 mg per day for more than 2 months, may lead to reversible peripheral sensory neuropathy. If symptoms of peripheral sensory neuropathy (paresthesia) occur, the dose should be adjusted and, if necessary, treatment discontinued.

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

Vitaxon® contains less than 1 mmol (39 mg)/dose of potassium, i.e. essentially "potassium-free".

Since Vitaxon® contains vitamin B6, caution should be exercised when administering the drug to patients with a history of peptic ulcer of the stomach and duodenum, or with marked impairments of renal and hepatic function.

Patients with neoplastic diseases, except in cases associated with megaloblastic anemia and vitamin B12 deficiency, should not be treated with this drug.

The drug should not be used in severe decompensated heart failure or angina pectoris.

Since Vitaxon® contains lidocaine, it should be noted that using disinfectants containing heavy metals at the injection site increases the risk of local reactions such as pain and swelling.

Since lidocaine has a pronounced antiarrhythmic effect and may itself act as an arrhythmogenic factor, potentially causing arrhythmias, the drug should be used with caution in individuals with a history of arrhythmia.

The drug should be used with caution in patients with moderate heart failure, moderate arterial hypotension, incomplete AV-block, intraventricular conduction disturbances, moderate hepatic and renal dysfunction (creatinine clearance 10 mL/min), respiratory function disorders, epilepsy, after cardiac surgery, in patients with genetic predisposition to hyperthermia, in debilitated patients, and in elderly patients.

ECG monitoring is mandatory during lidocaine administration. If sinus node dysfunction, prolonged P-Q interval, widened QRS complex, or development of a new arrhythmia occurs, the dose should be reduced or the drug discontinued.

Prior to lidocaine administration in cardiac disorders, serum potassium levels must be normalized (hypokalemia reduces lidocaine efficacy).

Intramuscular administration may increase creatinine concentration, potentially leading to misdiagnosis of acute myocardial infarction.

Use during pregnancy or breastfeeding

During pregnancy or breastfeeding, the recommended daily intake of vitamin B1 is 1.4–1.6 mg and of vitamin B6 is 2.4–2.6 mg. These doses may be exceeded during pregnancy if the patient has a deficiency of vitamins B1 and B6.

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

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

Ability to influence reaction speed when driving or operating machinery

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

If dizziness occurs during treatment with this drug, patients should refrain from driving or operating machinery.

Dosage and Administration

For intramuscular use.

In severe (acute) cases, treatment should begin with 2 ml of solution administered intramuscularly once daily until acute symptoms subside. For continuation of therapy, administer 2 ml (1 injection) 2–3 times per week. The treatment course should last at least 1 month.

Intramuscular injections should be administered into the upper outer quadrant of the gluteal muscle.

For maintenance or continuation of the therapeutic course of injections, or for prevention of relapse, Vitaxon® tablets, coated, are recommended.

Children

The drug is contraindicated in children.

Overdose

Vitamin B1 has a wide therapeutic range. Very high doses (over 10 g) may produce curare-like effects, inhibiting 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, and in isolated cases hypochromic anemia and seborrheic dermatitis have been reported after administration of more than 2 g per day.

Vitamin B12. After parenteral administration (in rare cases – 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 hypercoagulability.

Treatment: symptomatic therapy.

Lidocaine. Symptoms: psychomotor agitation, dizziness, general weakness, decreased arterial blood pressure, tremor, visual disturbances, tonic-clonic seizures, coma, collapse, possible atrioventricular 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 (noradrenaline, mesaton), in case of bradycardia – anticholinergics (0.5–1 mg atropine). Intubation, artificial ventilation of the lungs, and resuscitation measures may be necessary. Dialysis is ineffective.

Adverse reactions.

Long-term use (more than 6–12 months) at doses exceeding 50 mg of vitamin B6 daily may lead to peripheral sensory neuropathy, nervous excitement, malaise, dizziness, headache.

Gastrointestinal tract: gastrointestinal disturbances, including nausea, vomiting, diarrhea, abdominal pain, increased gastric juice acidity.

Immune system: hypersensitivity reactions (skin rashes, breathing difficulties, anaphylactic shock, Quincke's edema), increased sweating.

Skin: itching, urticaria, acneiform rashes; very rarely – generalized exfoliative dermatitis, angioneurotic edema.

Cardiovascular system: tachycardia, arrhythmias, bradycardia, slowed cardiac conduction, atrioventricular block, cardiac arrest, peripheral vasodilation, collapse; very rarely – tachycardia, increased/decreased arterial pressure, chest pain.

Nervous system: central nervous system excitation (when used in high doses), anxiety, headache, dizziness, sleep disturbances, confusion, drowsiness, loss of consciousness, coma; in patients with increased sensitivity – euphoria, tremor, trismus, motor restlessness, paresthesia, seizures.

Eyes: nystagmus, reversible blindness, diplopia, flickering "floaters" before the eyes, photophobia, conjunctivitis.

Ears: hearing disturbances, tinnitus, hyperacusis.

Respiratory system: dyspnea, rhinitis, respiratory depression or respiratory arrest.

Other: sensations of heat, cold or numbness in extremities, edema, weakness, malignant hyperthermia, sensory disturbances, motor block.

General disorders: reactions at the injection site.

With very rapid administration, systemic reactions such as seizures may occur.

Shelf life. 2 years.

Do not use the medication after the expiry date stated on the packaging.

Storage conditions.

Store in original packaging at a temperature between 2 °C and 8 °C. Do not freeze. Keep out of reach of children.

Incompatibility.

Pyridoxine is incompatible with drugs containing levodopa, as concomitant use enhances peripheral decarboxylation of levodopa, thereby reducing its antiparkinsonian effect.

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; in addition, thiamine loses its activity at increased pH values (above 3).

Vitamin B12 is incompatible with heavy metal salts.

Packaging.

2 mL in an ampoule.

5 or 10 ampoules per pack.

5 ampoules in a blister. 1 or 2 blisters per pack.

Prescription status. Prescription only.

Manufacturer. JSC "Farmak".

Manufacturer's location and address of business premises.

74, Kyrylivska St., Kyiv, 04080, Ukraine.