Vitaxon (solution)

Composition:

Active ingredients: thiamine hydrochloride, pyridoxine hydrochloride, cyanocobalamin;

1 mL solution contains 50 mg thiamine hydrochloride as calculated on 100% anhydrous substance, 50 mg pyridoxine hydrochloride as calculated on 100% dry substance, 0.5 mg cyanocobalamin as calculated on 100% dry substance;

Excipients: lidocaine hydrochloride, benzyl alcohol, sodium polyphosphate, potassium hexacyanoferrate III, sodium hydroxide, water for injection.

Pharmaceutical form

Solution for injections.

Basic physical and chemical properties: clear red liquid with specific odour.

Pharmacotherapeutic group

Vitamin В₁ combined with vitamin В₆ and/or В₁₂. АТС Code A11D B.

Pharmacological properties

Pharmacodynamics

Neurotropic vitamins B have a positive effect in inflammatory and degenerative nervous and musculoskeletal disorders. They are used to correct deficiency states, and in high doses they have an analgesic effect, improve blood circulation and nervous system and haematopoiesis.

Vitamin B₁ is an essential active substance. In the body, Vitamin B₁ is phosphorylated to biologically active thiamine diphosphate (cocarboxylase) and thiamine triphosphate (TTP). Thiamine diphosphate as a coenzyme is involved in important functions of carbohydrate metabolism, which are crucial in the metabolic processes of nervous tissue, and affect the conduction of nerve impulses at synapses. In vitamin B₁ deficiency in tissues, metabolites, primarily lactic and pyruvic acids, accumulate leading to various nervous pathological states and disorders.

Vitamin B₆ is in its phosphorylated form (pyridoxal-5′-phosphate, PALP) is a coenzyme of several enzymes interacting in general non-oxidative amino acid metabolism. By decarboxylation they participate in the formation of physiologically active amines (e.g., epinephrine, histamine, serotonin, dopamine, tyramine) by transamination in anabolic and catabolic metabolic processes (for example, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, gamma-aminobutyric acid, α-ketoglutarate transaminase) as well as in various processes of synthesis and cleavage of amino acids. Vitamin B₆ acts on four different stages of tryptophan metabolism. During synthesis of haemoglobin vitamin B₆ catalyzes α-amino-β-ketoadinine acid.

Vitamin B₁₂ is essential for cell metabolism. It has an effect on haematopoiesis (external anti-anaemia factor), and is involved in the formation of choline, methionine, creatinine, nucleic acids, and is pain relieving.

Pharmacokinetics

Following parenteral administration thiamine is distributed in the body. Approximately 1 mg of thiamine is metabolized daily. Metabolites are excreted in urine. Dephosphorilation take place in kidneys. The biological elimination half-life is 0.35 hours. Accumulation of thiamine in the body does not occur due to weak solubility in fats.

Vitamin В₆ is phosphorilized and oxidized to pyridoxal-5′-phosphate. In plasma pyridoxal 5′-phosphate and pyridoxal are bound to albumin. Pyridoxal is the only form of transport in blood. Pyridoxal-5-phosphate bound to albumin is hydrolyzed by alkaline phosphatase to pyridoxal to pass through the cell membrane.

Following parenteral administration Vitamin B₁₂ forms transport protein complexes that are rapidly absorbed by the liver, bone marrow and other proliferative organs. Vitamin B₁₂ enters the bile and takes part in the enterohepatic circulation. Vitamin B₁₂ penetrates through placenta.

Clinical particulars

Indications

Neurological manifestations of any origin: neuritis, neuralgias, polyneuropathy (diabetic, alcoholic), radicular syndrome, optic neuritis, facial palsy.

Contraindications

Hypersensitivity to any drug components, acute cardiac conduction abnormalities, acute decompensated heart failure.

Vitamin B₁ is contraindicated in allergic reactions.

Vitamin B₆ is contraindicated in acute gastric and duodenal ulcer (possible increased gastric acid).

Vitamin B₁₂ is contraindicated in erythraemia, polycythaemia, thromboembolism.

Lidocaine. Increased hypersensitivity to lidocaine, other amide local anaesthetics, a history of epileptiform convulsions with lidocaine, severe bradycardia, severe hypotension, cardiogenic shock, severe chronic heart failure (Class II-III), sick sinus syndrome, Wolff-Parkinson-White syndrome, Adams-Stokes syndrome, II and III degree atrioventricular (AV) block, hypovolemia, severe hepatic/renal impairment, porphyria, myasthenia.

Pregnancy and lactation.

Interactions with other medicinal products and other forms of interaction

Thiamine is inactivated by 5-fluorouracil since the latter competitively inhibits the phosphorylation of thiamine to thiamine pyrophosphate. Loop diuretics, e.g. furosemide that inhibit tubular reabsorption may cause increased excretion of thiamine in long-term therapy and, thus, lowering of the thiamine level.

Concomitant use with levodopa is contraindicated. If taken simultaneously with levodopa, vitamin B₆ can reduce the levodopa antiparkinson effect. The simultaneous administration of pyridoxine antagonists (e.g. isoniazide, hydralazine, penicillamine or cycloserine), oral contraceptives may increase the vitamin B₆ requirement.

Beverages containing sulphite (e.g. wine) enhance thiamine degradation.

Lidocaine potentiates inhibitory effect on the respiratory centre of anaesthetics (hexobarbital, thiopental sodium intravenously), hypnotics and sedatives and weakens the cardiotonic effect of digitoxin. Concomitant use with hypnotics and sedatives may increase inhibitory action on the central nervous system. Ethanol increases the inhibitory effect of lidocaine on respiration.

Adrenoreceptor blocking agents (incl. propranolol, nadolol) may slow down the hepatic metabolism of lidocaine, and enhance the effects of lidocaine (incl. toxic effects) and increase the risk of bradycardia and hypotension.

Curare-like drugs may increase muscle relaxation (possible paralysis of the respiratory muscles).

Norepinephrine, mexiletine may reduce clearance of lidocaine (increased toxicity).

Isadrin and glucagon may increase clearance of lidocaine.

Cimetidine, midazolam may increase lidocaine plasma concentration. Cimetidine displaces from its association with proteins and slows inactivation of lidocaine in the liver increasing the risk of adverse effects of lidocaine. Midazolam may moderately increase lidocaine blood concentration.

Anticonvulsants, barbiturates (incl. phenobarbital) may accelerate hepatic metabolism of lidocaine and decrease blood concentration.

Antiarrhythmics (amiodarone, verapamil, quinidine, ajmaline, disopyramide), anticonvulsants (hydantoin derivatives) potentiate cardiodepressive action; concomitant use with amiodarone can lead to seizures.

Novocaine, novocainamide may excite CNS and cause hallucinations if co-administered with lidocaine.

Monoamine oxidase inhibitors, aminazine, bupivacaine, amitriptyline, nortriptyline, imipramine: the combination with lidocaine may increase the risk of hypotension and prolong local anaesthetic effect of lidocaine.

Narcotic analgesics (morphine, etc.) may enhance analgesic effect of narcotic analgesics, cause respiratory depression if co-administered with lidocaine.

Prenylamine increases the risk of ventricular arrhythmias “torsade de pointes”.

Propafenone may increase duration and severity of CNS adverse effects.

Rifampicin may reduce the blood concentration of lidocaine.

Polymyxin B requires respiratory function monitoring.

Procainamide may cause hallucinations.

The effect of cardiac glycosides may weaken if co-administered with lidocaine.

Digitalis glycosides: lidocaine may exacerbate the severity of AV-block in intoxication.

Vasoconstrictors (epinephrine, methoxamine, phenylephrine) reduce absorption and prolong the effects of lidocaine if co-administered with lidocaine.

Guanadrel, guanethidine, mecamylamine, trimethaphan: the risk of severe hypotension and bradycardia increases in this combination for spinal and epidural anaesthesia.

β-adrenoreceptor blocking agents may reduce the hepatic metabolism of lidocaine, enhance the effects of lidocaine (including toxic effects) and increase the risk of bradycardia and hypotension. Lidocaine dose should be reduced in concomitant use of β-adrenoreceptor blocking agents and lidocaine.

Acetazolamide, thiazide and loop diuretics reduce the effect of lidocaine due to hypokalaemia if co-administered with lidocaine.

Anticoagulants (incl. ardeparin, dalteparin, danaparoid, enoxaparin, heparin, warfarin etc.) increase the risk of bleeding when used concomitantly with lidocaine.

Anticonvulsants, barbiturates (phenytoin) may accelerate hepatic metabolism of lidocaine, decrease blood concentration, potentiate cardiodepressive effect if co-administered with lidocaine.

Neuromuscular-blocking drugs in combination with lidocaine enhance the action of these drugs, as they reduce the conductivity of nerve impulses.

Special warnings and precautions for use

The product should not be administered by intravenous route. Intramuscular injections of vitamin B₁₂ may cause anaphylactoid reactions in patients with hypersensitivity.

Parenteral vitamin B₁₂ administration may temporarily impair the diagnosis of funicular myelosis or pernicious anaemia.

Long-term administration of vitamin B₆ (over 6-12 months) of daily dosages exceeding 50 mg or 1000 mg daily (more than two months) may cause reversible peripheral sensory neuropathy. If symptoms of peripheral sensory neuropathy (paraesthesia) occur, the dosage should be reviewed and treatment with the medicinal product discontinued, if necessary.

This product contains less than 1 mmol (23 mg)/dose sodium, i.e. is essentially “sodium free”.

Vitaxon^® contains less than 1 mmol (39 mg)/dose potassium, i.e. is essentially “potassium free”.

Vitaxon^® contains Vitamin B₆ which should be used with caution in patients with the history of gastric and duodenal ulcer, with severe renal and hepatic impairment.

Patients with tumours, except cases involving megaloblastic anaemia and vitamin B₁₂ deficiency should not use the drug.

The drug should not be used in severe cardiac decompensation and angina.

Vitaxon^® contains lidocaine; therefore the risk of local reactions (pain and swelling) increases if the injection site is treated with disinfectants containing heavy metals.

Since lidocaine has a strong antiarrhythmic action and can itself act as arrhythmogenic factor that may lead to the development of arrhythmias, the drug should be used with caution in persons with complaints of arrhythmia in the past.

Caution and lower doses should be administered in patients with moderate heart failure, moderate hypotension, incomplete AV-block, intraventricular conduction disorders, moderate hepatic and renal disorders (creatinine clearance 10 mL/min), impaired respiration, epilepsy, heart surgery, genetic predisposition to malignant hyperthermia, debilitated and elderly patients.

ECG monitoring is mandatory during lidocaine administration. The dose should be reduced/the product should be withdrawn in sinus node disorders, interval PQ prolongation, QRS complex or new arrhythmia episode.

Blood potassium level should be normalized before using lidocaine in heart diseases (hypokalaemia reduces effectiveness of lidocaine).

Intramuscular administration may increase creatinine concentrations which can interfere with the diagnosis of acute myocardial infarction.

Use during pregnancy and in nursing women

In pregnancy and lactation, the recommended daily allowance of vitamin B₁ is 1.4 mg to 1.6 mg, and for vitamin B₆ 2.4 mg to 2.6 mg. During pregnancy, these doses may be exceeded if the patient is B₁ and B₆ deficient.

Vitamins B₁, B₆ are excreted in breast milk. High-dose vitamin B₆ may inhibit milk production.

The product contains 100 mg of vitamin B₆ per ampoule, thus it should not be used during pregnancy and/or lactation.

Effects on ability to drive and use machines

The product does not affect the ability to drive and use machines.

Patients with dizziness during drug administration should avoid driving and using machines.

Posology and method of administration

For intramuscular administration.

In severe (acute) cases, treatment is initiated with 2 mL intramuscularly once daily to remove acute symptoms. For further treatment 2 mL (1 injection) should be administered 2-3 times a week. Treatment course is at least 1 month.

Intramuscular injections should be performed in the upper outer quadrant of the gluteus area.

Vitaxon^® film-coated tablets are recommended to maintain or continue the therapeutic course of injections or to prevent recurrence.

Paediatric patients

The product is not used in children.

Overdose

Vitamin B₁ has a wide therapeutic range. Very high doses (over 10 g) cause curare-like effect suppressing the conductivity of nerve impulses.

Vitamin B₆ has a very low toxicity.

Excessive use of vitamin B₆ at doses greater than 1 g daily for several months can lead to neurotoxic effects.

Neuropathies with ataxia and sensitivity disorders, cerebral convulsions with EEG changes as well as, in individual cases, hypochromic anaemia and seborrhoeic dermatitis have been described after administration of more than 2 g daily.

Vitamin B₁₂. Allergic reactions, eczematous skin alterations and a benign form of acne have been observed after high-dose parenteral administration (in rare cases after oral administration).

Long-term use at high doses may impair the activity of liver enzymes, cause cardiac pain, hypercoagulation.

Treatment: symptomatic treatment.

Lidocaine. Symptoms: psychomotor agitation, dizziness, general weakness, decreased blood pressure, tremor, blurred vision, tonic clonic seizures, coma, collapse, AV block, central nervous system depression, apnoea. The first symptoms of overdose arise in healthy volunteers at lidocaine blood concentration over 0.006 mg/kg, seizures occur at 0.01 mg/kg.

Treatment: termination of the drug administration, oxygen therapy, anticonvulsants, vasoconstrictors (noradrenaline, mesaton), anticholinergics (0.5-1 mg of atropine) in bradycardia. Intubation, artificial lung ventilation and resuscitation can be performed. Dialysis is ineffective.

Undesirable effects

Long-term treatment (more than 6-12 months) of a daily dosage > 50 mg of vitamin B₆ may, however, cause peripheral sensory neuropathy, nervous excitement, malaise, dizziness, headache.

Gastrointestinal disorders: gastrointestinal complaints such as nausea, vomiting, diarrhoea, abdominal pain, gastric hyperacidity.

Immune system disorders: hypersensitivity reactions including rash, respiratory disorders, anaphylactic shock, angioedema; hyperhidrosis.

Skin disorders: pruritus, urticaria, acne; very rare – generalized exfoliative dermatitis, angioedema.

Cardiac and vascular disorders: tachycardia, arrhythmia, bradycardia, slowing of cardiac conduction, AV heart block, cardiac arrest, peripheral vasodilatation, collapse; very rare – tachycardia, increased/decreased blood pressure, cardiac pain.

Nervous system disorders: excitation of the central nervous system (CNS) (if used in high doses), anxiety, headache, dizziness, sleep disturbances, confusion, drowsiness, loss of consciousness, coma; in patients with hypersensitivity – euphoria, tremor, locked jaw, restlessness, paraesthesia, convulsions.

Eye disorders: nystagmus, reversible blindness, double vision, muscae volitantes, photophobia, conjunctivitis.

Ear disorders: hearing disorders, tinnitus, hyperacusis.

Respiratory system disorders: dyspnoea, rhinitis, depression or respiratory arrest.

Others: fever or cold sensation or numbness of extremities, swelling, weakness, malignant hyperthermia, impaired sensitivity, motor block.

General disorders: reaction at the injection site.

Seizure-like systemic reactions may develop in case of very rapid parenteral administration.

Shelf-life

2 years.

Do not use after expiry date indicated on the carton.

Storage

Store in the original package at 2 °С to 8 °С. Do not freeze. Keep out of reach of children.

Incompatibilities

Pyridoxine is incompatible with drugs containing levodopa, because their concomitant use may enhance the peripheral decarboxylation of levodopa and, thus, reduce its antiparkinsonian effect.

Thiamine is incompatible with oxidising and reducing agents, mercury chloride, iodine, carbonate, acetate, tannic acid, ferric ammonium citrate, phenobarbital sodium, riboflavin, benzylpenicillin, glucose and metabisulphite because it is inactivated in their presence. Copper accelerates the breakdown of thiamine; in addition thiamine loses its effect at increased pH level (>pH 3).

Vitamin B₁₂ is incompatible with heavy metal salts.

Nature and contents of container

2 mL per ampoule.

5 or 10 ampoules per carton.

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

Prescription status

Prescription only.

Manufacturer

JSC Farmak.

Name and address of the manufacturer

74, Kyrylivska str., Kyiv, Ukraine, 04080.

Date of the last revision.

21.09.2021.