Tambo

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

Composition:

Active substances: thiamine hydrochloride, pyridoxine hydrochloride, cyanocobalamin;

1 ml of solution contains thiamine hydrochloride 50 mg, pyridoxine hydrochloride 50 mg, cyanocobalamin 0.5 mg;

Excipients: lidocaine hydrochloride, benzyl alcohol, potassium hexacyanoferrate III, sodium hexametaphosphate, sodium hydroxide, water for injections.

Pharmaceutical form.
Solution for injection.

Main physicochemical properties: clear red-colored solution.

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

Pharmacological Properties

Pharmacodynamics

Vitamins B of neurotropic action 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 possess analgesic properties, improve blood circulation, and help normalize the function of the nervous system and hematopoiesis.

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

Thiamine diphosphate acts as a coenzyme in essential carbohydrate metabolism processes, which are crucial for metabolic functions in nervous tissue and influence nerve impulse conduction in synapses. In case of vitamin B1 deficiency in tissues, metabolites accumulate, 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, PALP) serves 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 – in anabolic and catabolic metabolic processes (e.g., glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, γ-aminobutyric acid, α-ketoglutarate transaminase), as well as in various processes of amino acid breakdown and synthesis. Vitamin B6 acts at four different sites in 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 affects 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 0.35 hours. 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 bind to albumin. The transport 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 drug; acute impairment of cardiac conduction; acute form of decompensated heart failure.

Vitamin B1 is contraindicated in allergic reactions.

Vitamin B6 is contraindicated in peptic ulcer of the stomach and duodenum in the acute phase (since it may increase gastric juice acidity).

Vitamin B12 is contraindicated in erythremia, erythrocytosis, and 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 (grades II–III), sick sinus syndrome, Wolff–Parkinson–White syndrome, Adams–Stokes syndrome, second- and third-degree atrioventricular (AV) block, hypovolemia, severe hepatic/renal dysfunction, porphyria, myasthenia gravis.

Pregnancy and breastfeeding period.

Interaction with other medicinal products and other forms of interaction.

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 INH, 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.

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

Tambro contains benzyl alcohol. It is contraindicated 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 with caution and only when absolutely necessary, especially in patients with impaired liver or kidney function, as well as in pregnant and breastfeeding women.

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

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

Ability to influence reaction speed when driving vehicles or operating machinery.

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

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 vitamin B6 – 1.9 mg from the 4th month of pregnancy. During pregnancy, the medicinal product should be used only if vitamin B1 and B6 deficiency has been confirmed in the patient, as the safety of doses exceeding the recommended daily intake has not been established.

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

Vitamins B1, B6, and B12 are excreted in breast milk. High doses of vitamin B6 may reduce milk production.

The product contains 100 mg of vitamin B6 per 1 ampoule; therefore, it should not be used during pregnancy or breastfeeding.

The decision on using this medicinal product during pregnancy and breastfeeding should be made only after a physician has evaluated the benefit-risk ratio.

Children.

Not recommended for use in children.

Method of Administration and Dosage

Dosage

In cases of severe and acute pain, to achieve a rapid increase in the drug concentration in the blood, an initial injection (2 ml) should be administered once daily. After the acute phase has subsided and in mild disease states, administer one injection 2–3 times per week.

During therapy, weekly medical monitoring is recommended.

An early transition to oral therapy should be pursued whenever possible.

Method of Administration

Injections are administered deep intramuscularly (intramuscularly).

Warning to Prevent Accidental Intravenous Injection

Tambro is intended for intramuscular use only. Intravenous administration into the circulatory system is not permitted. In the event of accidental intravenous injection, medical monitoring or inpatient observation is required, depending on the severity of symptoms.

For maintenance or continuation of the therapeutic course of injections, or for prevention of relapse, a transition to oral therapy is recommended.

Overdose

Vitamin B1 has a wide therapeutic range. Very high doses (more than 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 seizures 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 after oral use), doses exceeding the recommended levels 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 agitation, dizziness, general weakness, decreased arterial 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 administration of the drug, oxygen therapy, anticonvulsants, vasoconstrictors (norepinephrine, mesaton), 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 not effective.

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).

Not known (frequency cannot be estimated from the available data).

Immune system disorders

Not known: benzyl alcohol may cause allergic reactions.

Very rare: hypersensitivity reactions (e.g. exanthema, dyspnea, shock, angioneurotic edema).

Cardiovascular system disorders

Very rare: tachycardia.

Skin and subcutaneous tissue disorders

Very rare: sweating, acne, skin reactions with pruritus and urticaria.

General disorders and administration site conditions

Not known: systemic reactions may occur due to rapid accumulation (e.g. accidental intravenous injection, injection into highly vascularized tissue) or overdose. Possible symptoms include dizziness, vomiting, bradycardia, cardiac arrhythmias, and seizures.

Burning sensation at the injection site.

Reporting of adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives should 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.

Store in the original packaging at a temperature not exceeding 25 ºC. Keep out of the reach of children.

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; furthermore, thiamine loses its activity at increased pH values (above 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 protect against this). Riboflavin, particularly under light exposure, also causes degradation; nicotinamide accelerates photolysis, whereas antioxidants exert an inhibitory effect.

Packaging.

2 ml in ampoules; 5 ampoules in a blister pack; 1 blister pack with the instructions for medical use in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

K. T. Rompharm Company S.R.L.

Manufacturer's address and place of business.

Strada Eroilor No. 1A, Otopeni, 075100, Ilfov County, Romania – Rompharm 1 and Rompharm 2 buildings.

Marketing Authorization Holder.

LLC "FORC-PHARMA DISTRIBUTION".

Address of the Marketing Authorization Holder.

132, Hryshkaivske Avenue, Kyiv, 03127, Ukraine.