Nerviplex-n
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NERVIPLEX-N (NERVIPLEX-N)
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 a beneficial effect on inflammatory and degenerative diseases of nerves and the musculoskeletal system. They are used to correct deficiency states, and in high doses they possess 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 in essential carbohydrate metabolism processes, which are crucial for metabolic functions in nervous tissue and influence nerve impulse conduction in synapses. In vitamin B1 deficiency, metabolites accumulate in tissues, primarily lactic and pyruvic acid, leading to various pathological conditions and disorders of 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 (adrenaline, 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 metabolic processes. It affects 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 21 minutes. 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. 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 organs. 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 it cannot be corrected by dietary means.
Contraindications.
Hypersensitivity to the components of the medicinal product; acute impairment of cardiac conduction; acute 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 (as 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 lidocaine-induced epileptiform seizures, severe bradycardia, severe arterial hypotension, cardiogenic shock, severe forms of chronic heart failure (grades II–III), sinus node dysfunction syndrome, Wolff-Parkinson-White syndrome, Adams-Stokes syndrome, second- and third-degree atrioventricular (AV) block, hypovolemia, severe hepatic/renal dysfunction, porphyria, myasthenia gravis.
The drug must not be used during pregnancy and/or breastfeeding.
Interaction with other medicinal products and other types of interactions.
Thiamine is completely degraded by sulfite-containing solutions. Other vitamins may be inactivated by the degradation products of vitamin B1. Therapeutic doses of vitamin B6 may reduce the effect of L-dopa. Interactions also 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. In addition, the drug interacts with sulfonamides.
In cases of overdose of local anesthetics, adrenaline and noradrenaline must not be used.
Special precautions for use.
Nerviplex-N contains lidocaine hydrochloride and therefore must be administered only by intramuscular injection. Intravenous (i.v.) administration into the bloodstream is prohibited. In case of accidental intravenous injection, medical monitoring or hospital observation may be required depending on the severity of symptoms.
Prolonged use of the drug for more than 6 months may lead to reversible peripheral sensory neuropathy.
The medicinal product contains 23 mg of sodium per ampoule (2 mL) and is therefore considered practically sodium-free.
Nerviplex-N contains benzyl alcohol. Benzyl alcohol has been associated with the risk of serious adverse effects ("gasping syndrome") in newborns and young children.
Large amounts of benzyl alcohol should be used with caution and only when absolutely necessary due to the risk of accumulation and toxicity (metabolic acidosis), 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 vitamin B6 is 1.9 mg from the 4th month of pregnancy. The use of this medicinal product during pregnancy is possible only when vitamin B1 and B6 deficiency has been confirmed, 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 into 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 or breastfeeding should be made by a physician only after assessing the risk/benefit ratio.
Ability to influence reaction rate when driving or operating machinery.
The drug does not affect the ability to drive or operate complex machinery.
Method of Administration and Dosage
Dosage.
In cases of severe and acute pain, to achieve a rapid increase in drug levels in the blood, an initial injection (2 ml) is administered once daily. After the acute phase has subsided and in mild disease states, administer one injection 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 early as possible.
Method of Administration.
Injections should be administered deep intramuscularly (intramuscularly).
Warning Regarding Prevention of Intravenous Injection.
The medicinal product is intended for intramuscular (i.m.) use only. Intravenous (i.v.) administration into the circulatory system is not permitted. In case of accidental intravenous injection, medical monitoring or hospital observation is required, depending on the severity of symptoms.
To maintain or continue the therapeutic course of injections or to prevent relapse, oral medications of a similar pharmacotherapeutic group are recommended.
Children. The drug is not intended for use in children.
Overdose.
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, 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) 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 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, anticonvulsant agents, vasoconstrictors (noradrenaline, 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 ineffective.
Side effects.
The frequency of adverse reactions is defined by the following categories:
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: 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, angioedema).
Cardiovascular system disorders: Very rare – tachycardia.
Skin and subcutaneous tissue disorders: Very rare – sweating, acne, pruritic skin reactions and urticaria.
General disorders and administration site conditions: Not known – systemic reactions may occur due to rapid accumulation (accidental intravenous injection, injection into tissue with high blood supply) or overdose. Dizziness, vomiting, bradycardia, cardiac arrhythmias, seizures. Burning sensation at the injection site.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report any suspected adverse reactions and lack of efficacy of the medicinal product via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.
Shelf life. 2 years.
Storage conditions. Keep out of the reach of children. Store in the original packaging at a temperature between 2 °C and 8 °C.
Incompatibilities.
Thiamine is incompatible with oxidizing and reducing compounds: 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 oxidizing and reducing compounds and with heavy metal salts.
In solutions containing thiamine, vitamin B12, like other components of the B-complex, is 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 have an inhibitory effect.
Packaging. 2 ml in an ampoule; packs of 5 or 100 ampoules; or 5 ampoules in a blister, 1 blister per pack.
Prescription status. Prescription only.
Manufacturer. Private Joint-Stock Company "Lekhim-Kharkiv".
Manufacturer's address and place of business.
36 Severina Pototskoho Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.