Pharmacological properties

Pharmacodynamics. neurotropic vitamins of group in have positive effect in inflammatory and degenerative diseases of nerves and the musculoskeletal system. they are appointed for elimination of scarce states, and in high doses they have analgeziruyushchy effect, improve blood circulation, normalize work of nervous system and process of a hemopoiesis.

_{1 Vitamin B} is important active agent. In an organism it is phosphorylated with education biologically active the tiamindifosfat (cocarboxylase) and the tiamintrifosfat (TTR).

Tiamindifosfat as coenzyme takes part in the important functions of carbohydrate metabolism which are crucial in exchange processes of nervous tissue influences carrying out a nervous impulse in synapses. At deficiency of _{1 vitamin B} in fabrics the accumulation of metabolites, first of all milk and pyroracemic acids happens that leads to various morbid conditions and dysfunctions of nervous system.

_{6 Vitamin B} in a fosforilirovanny form (piridoksal-5’ - phosphate — PALP) is coenzyme of a number of the enzymes interacting in the general not oxidizing metabolism of amino acids. By means of decarboxylation they participate in formation of physiologically active amines (for example adrenaline, a histamine, serotonin, a dopamine, tyramine), by means of transamination — in anabolic and catabolic processes of exchange (for example a glutamate-oksaloatsetattransaminaza, a glutamatpiruvattransaminaza, GAMK, a α-ketoglyutarattransaminaza) and also in various processes of splitting and synthesis of amino acids. _{6 vitamin B} affects 4 different stages of metabolism of tryptophane. In the course of synthesis of hemoglobin _{6 vitamin B} formation of α-amino-β-ketoadininovy acid catalyzes.

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_{12 Vitamin B} it is necessary for processes of cellular metabolism. He influences hemopoiesis function (external antianemic factor), takes part in formation of sincaline, methionine, creatinine, nucleic acids, has the anesthetizing effect.

Pharmacokinetics. At oral administration _{6 vitamin B} and its derivatives in the majority are quickly soaked up in an upper part of a digestive tract by passive diffusion and excreted within 2–5 h. After parenteral administration, thiamine is distributed in an organism. About 1 mg of thiamine is metabolized daily. Metabolites are removed with urine. Dephosphorylation happens in kidneys. The biological half-life period of thiamine is 0.35 h. Accumulation of thiamine in an organism does not happen thanks to weak dissolution in fats.

_{6 Vitamin B} is phosphorylated and oxidized to piridoksal-5 ’-phosphate. In blood plasma piridoksal-5’ - phosphate and piridoksal contact albumine. It is transported in shape piridoksalya. For passing through a cellular membrane piridoksal-5 ’-the phosphate connected with albumine is hydrolyzed by means of SF in piridoksal.

_{12 Vitamin B} after parenteral administration forms transport proteinaceous complexes which are quickly absorbed by a liver, marrow and other bodies. _{12 vitamin B} comes to bile and takes part in enterohepatic circulation, gets through a placental barrier.

Indication

Tablet. in the neurologic diseases caused by the proved vitamin deficiency v1, v6.

Solution for injections. Neurologic diseases of various origin: neuritis, neuralgia, polyneuropathy (diabetic, alcoholic), radicular syndrome, retrobulbar neuritis, damages of a facial nerve.

Use

Milgamm's

a tablet. apply inside, washing down with enough liquid.

Recommended dose makes 1 tablet a day. In individual cases the dose is raised and applied on 1 tablet 3 times a day.

should take the Pill entirely, washing down with liquid, after meal.

Duration of a course of treatment is defined by the doctor individually in each case. After the maximum period of treatment (4 weeks) the decision on correction and a dose decline of medicament is made.

Milgamm's

solution for injections. For introduction in oil.

In hard (sharp) cases treatment is begun with 2 ml of solution in oil of 1 times a day before elimination of acute symptoms. For continuation of treatment appoint 2 ml (1 injection) 2–3 times a week. A course of treatment — not less than 1 month

In oil an injection should be carried out in an upper external quadrant of a gluteus.

to

For maintenance or continuation of a course of therapy or for prevention of a recurrence recommends the medicament Milgamma, tablets, coated.

Contraindication

Tablet. hypersensitivity to medicament components. intake of vitamin v1 is contraindicated at allergic reactions. intake of vitamin v6 is contraindicated in a peptic ulcer of a stomach and duodenum in an aggravation stage (as increase in acidity of gastric juice is possible).

Period of pregnancy and feeding by a breast

Solution for injections. Hypersensitivity to medicament components; acute disorder of warm conductivity, acute form of dekompensirovanny heart failure.

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_{1 Vitamin B} it is contraindicated at allergic reactions. it is contraindicated to p to apply

_{6 Vitamin B} in ulcer of stomach and duodenum in an aggravation stage (as increase in acidity of gastric juice is possible). _{12 Vitamin B} it is contraindicated to p to apply

in an erythremia, a hyperglobulia, a thrombembolia.

Lidokain. Hypersensitivity to lidocaine or other amide mestnoanesteziruyushchy means, existence in the anamnesis of epileptiform spasms at intake of lidocaine, heavy bradycardia, heavy arterial hypotension, cardiogenic shock, severe forms of chronic heart failure (II—III degrees), a syndrome of weakness of a sinus node, cm WPW, Adams's syndrome — Stokes, AV blockade of II and III degree, a hypovolemia, heavy dysfunctions of livers/kidneys, a porphyria, a myasthenia.

Period of pregnancy and feeding by a breast.

Side effects

Tablet

from a digestive tract: nausea, vomiting, diarrhea, abdominal pain, increase in acidity of gastric juice.

from a cardiovascular system: tachycardia.

from the immune system: reactions of hypersensitivity, including an acute anaphylaxis; anaphylaxis; small tortoiseshell.

from skin: skin rashes, itching.

In extremely exceptional cases — a state of shock.

from nervous system: prolonged use (more than 6-12 months) in doses can daily lead more than 50 mg of _{6 vitamin B} to peripheral touch neuropathy, nervous excitement, dizziness, a headache.

from an endocrine system: prolactin discharge is inhibited.

Solution for injections. Prolonged use (more than 6-12 months) of _{6 vitamin B} in a dose of 50 mg can daily lead to peripheral touch neuropathy, nervous excitement, an indisposition, dizziness, a headache.

from a digestive tract: gastrointestinal disorders, including nausea, vomiting, diarrhea, abdominal pain, increase in acidity of gastric juice.

from the immune system: reactions of hypersensitivity (skin rash, breath disturbance, an acute anaphylaxis, a Quincke's edema), the increased sweating.

from skin: itching, urticaria, acne rash; extremely seldom — generalized exfoliative dermatitis, a Quincke's disease.

from a cardiovascular system: tachycardia, arrhythmia, bradycardia, delay of conductivity of heart, cross heart block, stop of warm activity, peripheral vazodilatation, collapse; very seldom — tachycardia, increase/decrease in the ABP, a heartache.

from nervous system: excitement of central nervous system (at use in high doses), concern, a headache, dizziness, a sleep disorder, confusion of consciousness, drowsiness, a loss of consciousness, a coma; patients with hypersensitivity have euphoria, a tremor, a lockjaw, motive concern, paresthesias, spasms.

from an organ of sight: a nystagmus, a reversible blindness, a diplopia, flashing of front sights before eyes, a photophobia, conjunctivitis.

from an organ of hearing: acoustical disturbances, sonitus, hyperacusia.

from a respiratory system: short wind, rhinitis, oppression or apnoea.

Others: feeling of heat, cold or numbness of extremities, hypostases, weakness, malignant hyperthermia, disturbances of sensitivity, motor block.

General disturbances: reactions in the injection site.

in case of very fast parenteral administration the development of system reactions in the form of spasms is possible

.

Special instructions

Tablet. the question of use of medicament of a milgam for treatment of patients with severe and acute form of dekompensirovanny heart failure is solved by the doctor individually, considering a condition of the patient.

At use of _{12 vitamin B} clinical picture and also laboratory analyses in a funicular myelosis or pernicious anemia can lose the specificity.

As medicament contains _{6 vitamin B} , it is necessary to appoint with care it the patient with ulcer of stomach and duodenum, a serious liver and renal failure in the anamnesis.

to Patients with new growths the medicament Milgama cannot be used, except for the cases connected with megaloblastny anemia and deficiency of _{12 vitamin B} . Drug is used in severe or acute form of dekompensirovanny warm activity and stenocardia.

At emergence of symptoms of peripheral touch neuropathy (paresthesia) needs to reconsider a dose and to suspend medicament Milgama use if it is necessary. At long reception (more than 6-12 months) of the daily doses exceeding 50 mg of _{6 vitamin B} , as well as at short-term reception (more than 2 months) more than 1 g of _{6 vitamin B} in day, were observed neuropathy, in this regard constant control at long reception is recommended.

Drug contains sucrose. Patients with rare hereditary intolerance of fructose, glyukozo-galaktozny malabsorption or insufficiency of invertase-isomaltase should not use this drug.

Solution for injections. It is not necessary to administer the medicament in / century. Injections in oil of _{12 vitamin B} can cause anaphylactoid reactions in patients with hypersensitivity.

Parenteral administration of _{12 vitamin B} can temporarily influence diagnosis of a funicular myelosis or pernicious anemia.

by Prolonged use of _{6 vitamin B} (more than 6-12 months) in doses is higher than 50 are mg daily or higher than 1000 mg/days (more than 2 months) can lead to reversible peripheral touch neuropathy. At emergence of symptoms of peripheral touch neuropathy (paresthesia) the dose adjustment of medicament or the termination of its reception are necessary.

Drug contains compounds of sodium. Patients who are on a saltless diet need to consider it. Each ampoule may contain residues of potassium.

As Milgamma contains _{6 vitamin B} , it is necessary to use with care medicament at patients with a round ulcer of a stomach and duodenum in the anamnesis, with the profound renal failures and a liver.

At patients with new growths, except the cases which are followed by megaloblastny anemia and deficiency of _{12 vitamin B} , should not use drug.

Drug is not used at a severe form of a decompensation of warm activity and stenocardia.

As Milgamma contains lidocaine, it is necessary to consider that when processing the place of an injection the disinfecting solutions containing heavy metals risk of development of local reaction in the form of morbidity and hypostasis increases.

As lidocaine has the significant antiarrhytmic effect and can act as the aritmogenny factor capable to lead to development of arrhythmia, it is necessary to use with care medicament at persons with complaints to arrhythmia in the anamnesis.

With care is applied at patients with heart failure of moderate degree, arterial hypotension of moderate degree, incomplete AV blockade, disturbance of intra ventricular conductivity, abnormal liver functions and kidneys of average degree (clearance of creatinine of 10 ml/min.), breath dysfunction, epilepsy, after heart surgeries, at genetic predisposition to a hyperthermia, at the weakened patients and patients of advanced age.

At lidocaine use obligatory is control of the ECG. In case of disturbances of activity of sinus node, lengthening of an interval of R-Q, the QRS expansion or at development of new arrhythmia it is necessary to lower a dose or to cancel drug.

Before use of lidocaine in heart diseases (the hypopotassemia reduces efficiency of lidocaine) needs to normalize potassium level in blood.

At introduction in oil the increase in concentration of creatinine is possible

that can lead to a mistake at establishment of the diagnosis of an acute myocardial infarction.

Use during pregnancy or feeding by a breast. During pregnancy and feeding by a breast the recommended daily use of _{1 vitamin B} makes 1.4-1.6 mg, for _{6 vitamin B} 2.4-2.6 mg. During pregnancy these doses can be exceeded if at the patient the vitamin deficiency In ₁ and In is noted ₆ .

_{1 Vitamins B} and Into ₆ get into breast milk. High doses of _{6 vitamin B} can reduce amount of milk.

Drug in the form of solution contains 100 mg of _{6 vitamin B} in ampoules therefore it should not be applied during pregnancy and feeding by a breast.

Children. The efficiency and safety of use of medicament for children are not established therefore it is not applied at patients of this age category.

Ability to influence speed of response at control of vehicles or other mechanisms. Drug does not affect ability to run vehicles and to work with difficult mechanisms.

If during treatment note dizziness, it is necessary to refrain from control of vehicles or work with other mechanisms.

Effect of thiamine is inactivated by

Interaction

fluorouratsily as the last competitively inhibits phosphorylation of thiamine in thiamine pyrophosphate. the loopback diuretics, for example furosemide braking a canalicular reabsorption at long therapy can cause increase in excretion of thiamine, thereby reducing its level.

Contraindicated simultaneous use with a levodopa as _{6 vitamin B} can reduce expressiveness of protivoparkinsonichesky action of a levodopa. The concomitant use with antagonists of a pyridoxine (for example an isoniazid, gidralazin, Penicillaminum or Cycloserinum), oral contraceptives can increase the need for _{6 vitamin B} .

Consumption of the drinks containing sulfites (for example wine), increases thiamine degradation.

Lidokain strengthens the oppressing action on a respiratory center of anesthetics (hexobarbital, sodium thiopental in / c), hypnotic medicaments and sedatives; weakens cardiotonic influence of digitoxin. At simultaneous use with hypnotic medicaments and sedatives strengthening of the oppressing action on central nervous system is possible.

Ethanol strengthens the oppressing effect of lidocaine on breath.

Blockers of adrenoceptors (including propranolol, Nadololum) slow down metabolism of lidocaine in a liver, enhance effects of lidocaine (including toxic) and increase risk of developing bradycardia and hypotension.

Kurarepodobny medicaments — muscle relaxation deepening is possible (to paralysis of respiratory muscles).

Norepinephrinum, meksiletin — amplifies toxicity of lidocaine (the clearance of lidocaine decreases).

Isadrinum and a glucagon — raises clearance of lidocaine.

Cimetidinum, midazolam — raises concentration of lidocaine in blood plasma. Cimetidinum forces out from communication with proteins and slows down a lidocaine inactivation in a liver that leads to increase in risk of strengthening of side effect of lidocaine. Midazolam moderately increases concentration of lidocaine in blood.

Anticonvulsants, barbiturates (including phenobarbital) — acceleration of metabolism of lidocaine in a liver, decrease in concentration in blood is possible.

Antiarrhytmic means (Amiodaronum, verapamil, quinidine, Ajmalinum, Disopyramidum), anticonvulsant medicaments (hydantoin derivatives) — cardiodepressive action amplifies; simultaneous use with Amiodaronum can lead to development of spasms.

Novocaine, novokainamid — at the combined use with lidocaine the excitement of central nervous system and developing of hallucinations is possible

.

MAO Inhibitors, aminazine, buvikain, amitriptyline, nortriptilin, Imipraminum — at the combined use with lidocaine raises risk of developing arterial hypotension and mestnoanesteziruyushchy effect of lidocaine is prolonged.

Narcotic analgetics (morphine, etc.) — at the combined use with lidocaine the analgeziruyushchy effect of narcotic analgetics increases and also respiratory depression amplifies.

Prenylaminum — raises risk of developing ventricular arrhythmia on type a pirouette.

Propafenon — increase in duration and weight of side effects from central nervous system is possible.

Rifampitsin — decrease in concentration of lidocaine in blood is possible.

Polymyxin B — should control breath function.

Prokainamid — hallucinations are possible.

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Cardiac glycosides — at the combined use with lidocaine weakens cardiotonic effect of cardiac glycosides.

foxglove Glycosides — against the background of intoxication lidocaine can increase weight of AV blockade.

Vasoconstrictors (epinephrine, metoksamin, Phenylephrinum) — at the combined use with lidocaine promote delay of absorption of lidocaine and prolong action of the last.

Guanadrel, guanetidin, mekamilamin, trimetafan — at the combined use for spinal and epidural anesthesia raises risk of the profound hypotension and bradycardia.

Blockers of β-adrenoceptors — at the combined use slow down metabolism of lidocaine in a liver, effects of lidocaine amplify (including toxic), risk of developing bradycardia and arterial hypotension increases. At simultaneous use of blockers of β-adrenoceptors and lidocaine it is necessary to lower a dose of the last.

Acetazoleamide, thiazide and loopback diuretics — at the combined use with lidocaine as a result of development of a hypopotassemia decreases effect of the last.

Anticoagulants (including ardeparin, dalteparin, danaparoid, enoksaparin, heparin, warfarin, etc.) — at the combined use with lidocaine the risk of developing bleedings increases.

Anticonvulsants, barbiturates (Phenytoinum) — at the combined use with lidocaine the acceleration of metabolism of lidocaine in a liver, decrease in concentration in blood, strengthening of cardiodepressive effect is possible

.

Drugs which cause neuromuscular transmission blockade — at the combined use with lidocaine the effect of the medicaments causing neuromuscular transmission blockade as the last reduce conductivity of nervous impulses amplifies.

Incompatibility. The pyridoxine is incompatible with the medicaments containing a levodopa as at simultaneous use the peripheral decarboxylation of the last amplifies and, thus, the expressiveness of its antiparkinsonichesky action decreases.

Thiamine is incompatible

with the oxidizing and reducing connections: mercury chloride, iodide, a carbonate, acetate, tannin acid, iron ammonium citrate and also with sodium phenobarbital, Riboflavinum, benzylpenicillin, glucose and metabisulphite as it is inactivated at their presence. Copper accelerates thiamine disintegration; besides, thiamine loses the activity at increase rn 3. _{12 vitamin B} is incompatible with salts of heavy metals.

Overdose

Vitamin v1 has wide therapeutic range. very high doses (more than 10 g) show kurarepodobny effect, suppressing conductivity of nervous impulses.

_{6 Vitamin B} has very much hypotoxicity.

Excessive use of _{6 vitamin B} in doses more than 1 g/days within several months can result

in neurotoxic effect.

Neuropathy with an ataxy and sensitivity disorders, cerebral spasms with changes on EEG and also in some cases hypochromia anemia and seborrheal dermatitis were described after introduction in a dose higher than 2 g/days

_{12 Vitamin B} : after parenteral administration (in rare instances — after oral administration) in doses higher, than recommended, noted allergic reactions, eczematic skin disturbances and a benign form of an acne.

At prolonged use in high doses the disturbance of activity of enzymes of a liver, pain in heart, hypercoagulation are possible

.

Treatment: symptomatic therapy.

Lidokain. Symptoms: psychomotor excitement, dizziness, the general weakness, decrease in the ABP, a tremor, a disorder of vision, toniko-clonic spasms, a coma, collapse, AV blockade, oppression of central nervous system, an apnoea is possible. The first symptoms of overdose at healthy people arise at concentration of lidocaine in blood of 0.006 mg/kg of body weight, a spasm — at 0.01 mg/kg.

Treatment: the termination of administration of drug, oxygenotherapy, anticonvulsants, vasoconstrictors (Norepinephrinum, a phenylephine hydrochloride), in bradycardia — cholinolytics (0.5-1 mg of atropine). Carrying out an intubation, IVL, resuscitation actions is possible. Dialysis is inefficient.

Storage conditions

Tablet: at a temperature not above 25 °C.

Solution for injections: at a temperature not above 2-8 °C in original packing for protection against light.