Pharmacological properties
Pharmacodynamics. Neurotropic vitamins of group B have a beneficial effect on inflammatory and degenerative diseases of the nerves and musculoskeletal system. They are prescribed to eliminate deficiency states, and in large doses have analgesic properties, improve blood circulation, normalize the functioning of the nervous system and the process of hematopoiesis.
Vitamin B1 is a very important active substance. In the body, it is phosphorylated to form biologically active thiamine diphosphate (cocarboxylase) and thiamine triphosphate (TTP).
Thiamine diphosphate as a coenzyme participates in important functions of carbohydrate metabolism, is of crucial importance in metabolic processes of nervous tissue, affects the conduction of nerve impulses in synapses. With a deficiency of vitamin B 1 in tissues, metabolites accumulate, primarily lactic and pyruvic acids, which leads to various pathological conditions and disorders of the nervous system.
Vitamin B6 in its phosphorylated form (pyridoxal-5'-phosphate - PALP) is a coenzyme of a number of enzymes that interact in the general non-oxidative metabolism of amino acids. Through decarboxylation, they are involved in the formation of physiologically active amines (e.g. adrenaline, histamine, serotonin, dopamine, tyramine), through transamination - in anabolic and catabolic metabolic processes (e.g. glutamate-oxaloacetate transaminase, glutamatepyruvate transaminase, GABA, α-ketoglutarate transaminase), as well as in various processes of amino acid breakdown and synthesis. Vitamin B6 acts on 4 different sites of tryptophan metabolism. In the process of hemoglobin synthesis, vitamin B6 catalyzes the formation of α-amino-β-ketoadenic acid.
Vitamin B12 is necessary for cellular metabolism. It affects the function of hematopoiesis (extrinsic anti-anemic factor), participates in the formation of choline, methionine, creatinine, nucleic acids, and has an analgesic effect.
Pharmacokinetics. When administered orally, vitamin B6 and its derivatives are mostly rapidly absorbed in the upper digestive tract by passive diffusion and excreted within 2-5 hours. After parenteral administration, thiamine is distributed in the body. About 1 mg of thiamine is metabolized daily. Metabolites are excreted in the 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 poor solubility in fats.
Vitamin B6 is phosphorylated and oxidized to pyridoxal-5'-phosphate. In blood plasma, pyridoxal-5'-phosphate and pyridoxal are bound to albumin. It is transported in the form of pyridoxal. To pass through the cell membrane, pyridoxal-5'-phosphate, bound to albumin, is hydrolyzed by LF to pyridoxal.
Vitamin B12 after parenteral administration forms transport protein complexes that are rapidly absorbed by the liver, bone marrow and other organs. Vitamin B12 enters the bile and participates in the enterohepatic circulation, penetrates the placental barrier.
Indication
Tablets. for neurological diseases caused by proven deficiency of vitamins B1, B6.
Solution for injection. Neurological diseases of various origins: neuritis, neuralgia, polyneuropathy (diabetic, alcoholic), radicular syndrome, retrobulbar neuritis, facial nerve damage.
Application
Milgamma tablets are taken orally, washed down with a sufficient amount of liquid.
The recommended dose is 1 tablet per day. In individual cases, the dose is increased and used 1 tablet 3 times a day.
The tablets should be taken whole with liquid, after meals.
The duration of the course of treatment is determined by the doctor individually in each case. After the maximum period of treatment (4 weeks), a decision is made to correct and reduce the dose of the drug.
Milgamma solution for injection. For intramuscular administration.
In severe (acute) cases, treatment is started with 2 ml of the solution i/m 1 time per day until the acute symptoms are eliminated. To continue treatment, 2 ml (1 injection) is prescribed 2-3 times a week. The course of treatment is at least 1 month.
The intramuscular injection should be performed in the upper outer quadrant of the gluteal muscle.
To maintain or continue the course of therapy or to prevent relapse, the drug Milgamma, film-coated tablets, is recommended.
Contraindication
Tablets. Hypersensitivity to the components of the drug. Taking vitamin B1 is contraindicated in allergic reactions. Taking vitamin B6 is contraindicated in gastric and duodenal ulcers in the acute stage (since increased acidity of gastric juice is possible).
Pregnancy and breastfeeding
Solution for injection. Hypersensitivity to the components of the drug; acute cardiac conduction disorders, acute form of decompensated heart failure.
Vitamin B1 is contraindicated in allergic reactions.
Vitamin B6 is contraindicated for use in cases of gastric and duodenal ulcers in the acute stage (since it may increase the acidity of gastric juice).
Lidocaine. Hypersensitivity to lidocaine or other amide local anesthetics, history of epileptiform seizures when taking lidocaine, severe bradycardia, severe hypotension, cardiogenic shock, severe forms of chronic heart failure (II-III degree), sick sinus syndrome, WPW syndrome, Adams-Stokes syndrome, AV block II and III degree, hypovolemia, severe liver / kidney dysfunction, porphyria, myasthenia gravis.
Pregnancy and breastfeeding.
Side effects
pills
Gastrointestinal tract: nausea, vomiting, diarrhea, abdominal pain, increased acidity of gastric juice.
Cardiovascular system: tachycardia.
Immune system disorders: hypersensitivity reactions, including anaphylactic shock; anaphylaxis; urticaria.
Skin: skin rashes, itching.
In extremely rare cases, shock.
On the part of the nervous system: long-term use (over 6-12 months) in doses of more than 50 mg of vitamin B6 daily can lead to peripheral sensory neuropathy, nervous excitement, dizziness, and headache.
On the part of the endocrine system: a decrease in prolactin secretion was noted.
Solution for injection. Long-term use (over 6-12 months) of vitamin B6 at a dose of 50 mg daily can lead to peripheral sensory neuropathy, nervous excitement, malaise, dizziness, and headache.
Gastrointestinal tract: gastrointestinal disorders, including nausea, vomiting, diarrhea, abdominal pain, increased acidity of gastric juice.
On the part of the immune system: hypersensitivity reactions (skin rash, respiratory distress, anaphylactic shock, angioedema), increased sweating.
Skin: itching, urticaria, rash; extremely rarely - generalized exfoliative dermatitis, angioedema.
From the cardiovascular system: tachycardia, arrhythmia, bradycardia, slowing of cardiac conduction, transverse heart block, cardiac arrest, peripheral vasodilation, collapse; very rarely - tachycardia, increase / decrease in blood pressure, heart pain.
From the nervous system: excitation of the central nervous system (when used in high doses), anxiety, headache, dizziness, sleep disturbances, confusion, drowsiness, loss of consciousness, coma; in patients with hypersensitivity - euphoria, tremor, trismus, motor restlessness, paresthesias, convulsions.
On the part of the organ of vision: nystagmus, reversible blindness, diplopia, flashing flies before the eyes, photophobia, conjunctivitis.
On the part of the organ of hearing: hearing impairment, tinnitus, hyperacusis.
Respiratory system: shortness of breath, rhinitis, respiratory depression or arrest.
Others: sensation of heat, cold or numbness of the extremities, edema, weakness, malignant hyperthermia, sensory disturbances, motor block.
General disorders: injection site reactions.
In the case of very rapid parenteral administration, systemic reactions in the form of convulsions may develop.
Special instructions
Tablets. The question of using the drug Milgamma for the treatment of patients with severe and acute decompensated heart failure is decided by the doctor individually, taking into account the patient's condition.
When using vitamin B12, the clinical picture, as well as laboratory tests in funicular myelosis or pernicious anemia, may lose their specificity.
Since the drug contains vitamin B6, it should be prescribed with caution to patients with gastric and duodenal ulcers, severe liver and kidney failure in history.
Patients with neoplasms should not use the drug Milgamma, except in cases associated with megaloblastic anemia and vitamin B 12 deficiency. The drug is used for severe or acute forms of decompensated cardiac activity and angina pectoris.
If signs of peripheral sensory neuropathy (paresthesia) appear, the dose should be reviewed and the use of Milgamma should be discontinued, if necessary. Neuropathies have been observed with long-term (more than 6-12 months) daily doses exceeding 50 mg of vitamin B6, as well as with short-term (more than 2 months) doses exceeding 1 g of vitamin B6 per day, therefore constant monitoring is recommended with long-term use.
This medicine contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Solution for injection. The drug should not be administered intravenously. Intramuscular injections of vitamin B12 may cause anaphylactoid reactions in patients with hypersensitivity.
Parenteral administration of vitamin B12 may temporarily interfere with the diagnosis of funicular myelosis or pernicious anemia.
Long-term use of vitamin B6 (more than 6-12 months) in doses above 50 mg daily or above 1000 mg/day (more than 2 months) may lead to reversible peripheral sensory neuropathy. If symptoms of peripheral sensory neuropathy (paresthesia) occur, dose adjustment of the drug or discontinuation of its administration is necessary.
The drug contains sodium compounds. This should be taken into account by patients on a salt-free diet. Each ampoule may contain traces of potassium.
The drug should not be used in patients with neoplasms, except in cases accompanied by megaloblastic anemia and vitamin B12 deficiency.
The drug is not used in severe forms of cardiac decompensation and angina pectoris.
Since Milgamma contains lidocaine, it should be noted that when treating the injection site with disinfectant solutions containing heavy metals, the risk of developing a local reaction in the form of soreness and swelling increases.
Since lidocaine has a pronounced antiarrhythmic effect and can itself act as an arrhythmogenic factor that can lead to the development of arrhythmia, the drug should be used with caution in individuals with a history of arrhythmia.
Use with caution in patients with moderate heart failure, moderate hypotension, incomplete AV block, impaired intraventricular conduction, moderate liver and kidney function (creatinine clearance 10 ml/min), impaired respiratory function, epilepsy, after heart surgery, with a genetic predisposition to hyperthermia, in debilitated patients and elderly patients.
When using lidocaine, ECG monitoring is mandatory. In case of sinus node dysfunction, prolongation of the P-Q interval, QRS widening, or the development of a new arrhythmia, the dose should be reduced or the drug should be discontinued.
Before using lidocaine for heart disease (hypokalemia reduces the effectiveness of lidocaine), it is necessary to normalize the level of potassium in the blood.
With i / m administration, an increase in creatinine concentration is possible, which can lead to an error in establishing the diagnosis of acute myocardial infarction.
Use during pregnancy or breastfeeding. During pregnancy and breastfeeding, the recommended daily intake of vitamin B1 is 1.4-1.6 mg, for vitamin B6 2.4-2.6 mg. During pregnancy, these doses may be exceeded 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 supply.
The drug in solution form contains 100 mg of vitamin B6 in ampoules, so it should not be used during pregnancy and breastfeeding.
Children. The efficacy and safety of the drug in children have not been established, therefore it is not used in patients of this age category.
Ability to influence the reaction speed when driving vehicles or other mechanisms. The drug does not affect the ability to drive vehicles and work with complex mechanisms.
If dizziness is noted during treatment, you should refrain from driving vehicles or operating other mechanisms.
Interactions
The action of thiamine is inactivated by fluorouracil, since the latter competitively inhibits the phosphorylation of thiamine to thiamine pyrophosphate. Loop diuretics, such as furosemide, which inhibit tubular reabsorption, can cause increased excretion of thiamine with prolonged therapy, thereby reducing its level.
Concomitant use with levodopa is contraindicated, as vitamin B6 may reduce the antiparkinsonian effect of levodopa. Concomitant use with pyridoxine antagonists (e.g. isoniazid, hydralazine, penicillamine or cycloserine), oral contraceptives may increase the need for vitamin B6.
Consumption of beverages containing sulfites (e.g. wine) increases the degradation of thiamine.
Lidocaine enhances the inhibitory effect on the respiratory center of anesthetics (hexobarbital, thiopental sodium IV), hypnotics and sedatives; weakens the cardiotonic effect of digitoxin. When used simultaneously with hypnotics and sedatives, an increase in the depressing effect on the CNS is possible.
Ethanol enhances the inhibitory effect of lidocaine on respiration.
Adrenoceptor blockers (including propranolol, nadolol) slow down the metabolism of lidocaine in the liver, enhance the effects of lidocaine (including toxic ones) and increase the risk of developing bradycardia and hypotension.
Curare-like drugs - possible deepening of myorelaxation (up to paralysis of the respiratory muscles).
Norepinephrine, mexiletine - increases the toxicity of lidocaine (decreases the clearance of lidocaine).
Isadrin and glucagon - increases the clearance of lidocaine.
Cimetidine, midazolam - increases the concentration of lidocaine in the blood plasma. Cimetidine displaces it from protein binding and slows down the inactivation of lidocaine in the liver, which leads to an increased risk of increased side effects of lidocaine. Midazolam moderately increases the concentration of lidocaine in the blood.
Anticonvulsants, barbiturates (including phenobarbital) - possible acceleration of lidocaine metabolism in the liver, decrease in blood concentration.
Antiarrhythmic drugs (amiodarone, verapamil, quinidine, ajmalin, disopyramide), anticonvulsants (hydantoin derivatives) - cardiodepressive effect is enhanced; simultaneous use with amiodarone may lead to the development of seizures.
Novocaine, novocainamide - when used in combination with lidocaine, CNS disorders and hallucinations are possible.
Narcotic analgesics (morphine, etc.) - when used in combination with lidocaine, the analgesic effect of narcotic analgesics increases, and respiratory depression also increases.
Prenylamine - increases the risk of developing torsades de pointes ventricular arrhythmia.
Propafenone - possible increase in the duration and severity of CNS side effects.
Rifampicin - a possible decrease in the concentration of lidocaine in the blood.
Polymyxin B - respiratory function should be monitored.
Procainamide - possible hallucinations.
Cardiac glycosides - when combined with lidocaine, the cardiotonic effect of cardiac glycosides is weakened.
Digitalis glycosides - against the background of lidocaine intoxication, it can increase the severity of AV blockade.
Vasoconstrictors (adrenaline, methoxamine, phenylephrine) - when used in combination with lidocaine, they help slow down the absorption of lidocaine and prolong the effect of the latter.
Guanadrel, guanethidine, mecamylamine, trimetaphan - when used in combination for spinal and epidural anesthesia, the risk of severe hypotension and bradycardia increases.
β-adrenergic blockers - when used in combination, they slow down the metabolism of lidocaine in the liver, enhance the effects of lidocaine (including toxic ones), and increase the risk of bradycardia and hypotension. When using β-adrenergic blockers and lidocaine simultaneously, it is necessary to reduce the dose of the latter.
Acetazolamide, thiazide and loop diuretics - when used in combination with lidocaine, the effect of the latter is reduced as a result of the development of hypokalemia.
Anticoagulants (including ardeparin, dalteparin, danaparoid, enoxaparin, heparin, warfarin, etc.) - when used in combination with lidocaine, the risk of bleeding increases.
Anticonvulsants, barbiturates (phenytoin) - when used in combination with lidocaine, it is possible to accelerate the metabolism of lidocaine in the liver, reduce its concentration in the blood, and increase the cardiodepressive effect.
Drugs that cause blockade of neuromuscular transmission - when used in combination with lidocaine, the effect of drugs that cause blockade of neuromuscular transmission is enhanced, since the latter reduce the conductivity of nerve impulses.
Incompatibility. Pyridoxine is incompatible with drugs containing levodopa, since simultaneous use increases the peripheral decarboxylation of levodopa and, thus, reduces the severity of its antiparkinsonian effect.
Thiamine is incompatible with oxidizing and reducing compounds: mercuric chloride, iodide, carbonate, acetate, tannic acid, ammonium ferric citrate, as well as with sodium phenobarbital, riboflavin, benzylpenicillin, glucose and metabisulfite, since it is inactivated in their presence. Copper accelerates the decomposition of thiamine; in addition, thiamine loses its activity when the pH increases to 3. Vitamin B 12 is incompatible with salts of heavy metals.
Overdose
Vitamin B1 has a wide therapeutic range. Very high doses (more than 10 g) exhibit a curare-like effect, inhibiting the conduction of nerve impulses.
Vitamin B6 has very low toxicity.
Excessive use of vitamin B6 in doses greater than 1 g/day for several months can 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 described after administration of doses above 2 g/day.
Vitamin B12: after parenteral administration (in some cases - after oral administration) in doses higher than recommended, allergic reactions, eczematous skin disorders and a benign form of acne have been noted.
With prolonged use in high doses, liver enzyme activity disorders, pain in the heart area, and hypercoagulation are possible.
Treatment: therapy is symptomatic.
Lidocaine. Symptoms: psychomotor agitation, dizziness, general weakness, decreased blood pressure, tremor, visual impairment, tonic-clonic convulsions, coma, collapse, possible AV block, central nervous system depression, respiratory arrest. The first symptoms of overdose in healthy people occur at a lidocaine blood concentration of 0.006 mg/kg of body weight, convulsions - at 0.01 mg/kg.
Treatment: discontinuation of the drug, oxygen therapy, anticonvulsants, vasoconstrictors (noradrenaline, mezaton), with bradycardia - anticholinergics (0.5-1 mg of atropine). Intubation, mechanical ventilation, and resuscitation measures are possible. Dialysis is ineffective.
Storage conditions
Tablets: at a temperature not exceeding 25 °C.
Solution for injection: at a temperature not exceeding 2-8 °C in the original packaging to protect from light.
