Sibazonum

General characteristics. Structure:

Active ingredient: 5 mg of diazepam (Sibazonum) in 1 ml of solution.

Excipients: ethanol in terms of 100% alcohol, sodium chloride, propylene glycol, a macrogoal-400 (poly(ethylene oxide)-400), water for injections.

Pharmacological properties:

Pharmacodynamics. The mechanism of effect of diazepam is caused by stimulation of benzodiazepine receptors supramolecular GAMK-benzodiazepin-hlorionofor a receptor complex, GAMK leading to strengthening of an inhibiting effect (piperidic acid - a mediator pre-and postsynaptic braking in all departments of the central nervous system) on transfer of nervous impulses. Stimuliyoruyet the benzodiazepine receptors located in the allosteric center of postsynaptic GAMK-receptors of the ascending activating reticular formation of a brainstem and internuncial neurons of side horns of a spinal cord; reduces excitability of subcrustal structures of a brain (a limbic sisyotema, a thalamus, a hypothalamus), brakes polisinaptichesky spinal reflexes.

Anxiolytic action is caused by influence on an amygdaloid komyopleks of limbic system and the napryazheyoniya, weakening of alarm, fear, concern is shown in reduction emotional.

Sedation is caused by influence on a reticular formation of a trunk of a brain and nonspecific kernels of a thalamus and is shown by reduction of symptomatology of a neurotic origin (alarm, fear).

The main mechanism of somnolent action consists in oppression of cells of a reyotikulyarny formation of a trunk of a brain.

Anticonvulsant action is implemented by strengthening of presynaptic braking. Distribution of epileptogenic activity is suppressed, but the excited condition of the center does not sniyomatsya.

The central myorelaxation action is caused by braking of the polisinaptichesky spinal afferent braking ways (to a lesser extent and monosinaptichesky). Possibly and direct inhibition of motor nerves and function of muscles.

Having moderate sympatholytic activity, can cause snizheyony arterial pressure and expansion of coronary vessels. Raises a threshold of painful sensitivity. Suppresses sympathoadrenal and parasympathetic (including vestibular) paroxysms. Reduces night secretion of a gastric juice.

Effect of drug is observed by 2-7 day of treatment.

Practically does not influence productive symptomatology of psychotic genesis (acute crazy, hallucinatory, affective frustration), reduction of affective tension, crazy frustration nayoblyudatsya seldom.
At an abstinence syndrome at an alcoholism causes oslabyoleny agitations, a tremor, negativism, and also a tremens and gallyutsinayotion.

The therapeutic effect at patients with cardialgias, arrhythmias and paresthesias is observed by the end of 1 week.

Pharmacokinetics. Absorption is high. At intramuscular introduction absorption can be slow and non-constant. (depends on an injection site); at introduction a deltoyovidny muscle - absorption bystry and full. Bioavailability - 90%. Time of a dosyotizheniye of the maximum concentration (TCmax) - 0,5-1,5 h (intramusculary); ravnoyovesny concentration (Css) is reached at constant reception in 1-2 weeks.

Diazepam and its metabolites get through GEB (blood-brain barrier) and a placental barrier, the corresponding 1/10 parts of concentration in plasma are found in breast milk in концентраци­ях. Communication with proteins of plasma - 98%.

98-99% to pharmacological very active proizyovodny (desmetildiazepa) and less active are metabolized in a liver with participation of the fermental CYP2C19, CYP3A4, CYP3A5 and CYP3A7 system (temazepam and oxazepam).

It is removed by kidneys - 70% (in the form of glucuronides), in an invariable type of 1-2% and less than 10% - with a stake. Removal has two-phase, character: the pervoyonachalny phase of bystry and extensive distribution (an elimination half-life (T1/2) - 3 h) is followed by a long phase (T1/2 - 20-70 h). T1/2 of a desmetildiazepam - 30-100 h, temazepam - 9,5-12,4 h and oxazepam - 5-15 h.
T1/2 can be extended at newborns (to 30 h), patients of advanced and senile age (to 100 h) and at patients from a hepatonephric nedostatochnoyostyyu (to 4 days).

At repeated use accumulation of diazepam and its active metaboliyot considerable. Removal to a poyosla of the termination of treatment - slow since metabolites remain in blood in techeyony several days or even weeks belongs to benzodiazepines with long T1/2.

Indications to use:

Appoint at psychomotor excitement, including acute trevozhnoyo-phobic and alarming depressions, alcoholic psychoses with abstinence yavleyoniya; predeliriozny states and deliriums; epileptic statuyos and other convulsive states (tetanus, eclampsia); muscular spasms of a tsenyotralny origin at neurodegenerative diseases, including, at spine injuries, a lumbago, cervical radiculitis.

Are applied also in komyopleksny therapy of a myocardial infarction, to premedication at a defibrillation, at muscular spasms of a rheumatic origin and a vertebralny syndrome, to premedication at operational and difficult diagnostic interventions, to simplification of patrimonial activity; premature births (only at the end of the III triyomestr of pregnancy); premature peeling of a placenta.

Route of administration and doses:

Enter intravenously and intramusculary (it is deep in a large muscle). Vnutriyovenno is entered slowly into large veins with a speed no more than 1 ml a minute.

The dose of drug depends on a condition of the patient, a clinical picture of a zaboleyovaniye, sensitivity to Sibazonum and is defined individually.

At treatment of acute alarming states, excitement and fear by the adult appoint intramusculary in a dose 0,5-2 ml (2,5-10 mg). If necessary Sibazonum is entered repeatedly in the same dose, 3-4 hours later. Intravenously "the drug is administered in an initial dose 0,02-0,04 ml/kg of body weight (0,1-0,2 mg/kg); injections are repeated every 8 hours before disappearance of acute symptoms.

At injuries of a spinal cord drug is appointed the adult intramusculary in an initial dose of 2-4 ml (10-20 mg), to children in dependence, from age - 0,4-2 ml (2-10 mg).

At the epileptic status the adult enter in a dose 0,03-0,05 ml/kg (0,15-0,25 mg/kg) intravenously or intramusculary. In need of an injection it is possible to repeat in 30-60 minutes to the maximum daily dose 0,6 ml/kg (3 mg/kg). To children of 6 months enter 0,06-0,1 ml/kg (0,3-0,5 mg/kg) in a dose. The one-time doyoza for children should not exceed: for children up to 5 years - 5 mg (1 ml), are more senior than 5 years - 10 mg (2 ml). If necessary introduction can be repeated in 2-4 hours.

At tetanus drug, 0,02-0,06 ml/kg - (0,1-0,3 mg/kg) enter bucketed from 1 to 4 hours intravenously in a dose. To children from 6 months to 5 years - intramusculary or intravenously - 1-2 mg; to children 5 years - 5-10 mg are more senior. At a neobkhodiyomost the dose can be repeated.

At a myocardial infarction appoint in a dose 2 ml (10 mg) intramusculary, for premedication at a defibrillation enter intravenously in a dose 2-6 ml (10-30 mg). At muscular spasms of a rheumatic origin and a vertebralny syndrome vvoyodit in a dose 2 ml (10 mg) intramusculary.

At an eclampsia appoint intravenously in a dose 2-4 ml (10-20 mg) a day, and if necessary during crisis - to 14 ml (70 mg) a day. Use in doses can cause higher than 30 mg within 15 hours before childbirth in a newborn apnoea, arteriyoalny hypotension, a hypothermia.

For premedication in anesthesiology and surgery appoint the adult: on the eve of operation - 2-4 ml (10-20 mg) intramusculary, in 1 hour prior to an anesthesia - 2 ml (10 mg) intravenously or intramusculary, after operation - 1-2 ml (5-10 mg) intramusculary. For achievement of a short-term narcotic dream at difficult diagnostic (endoscopic) interventions intravenously enter 2-4 ml (10-20 mg).

Treatment of elderly patients should be begun with a half of a usual dose for adults, gradually raising it depending on efficiency of therapy and a pereyonosimost of drug.

Usually after stopping of an acute state and achievement of necessary therapeutic effect pass to purpose of Sibazonum in the form of tablets.

Features of use:

Intravenously solution of diazepam needs to be entered slowly, into a large vein at least within 1 min. on each 5 mg (1 ml) of drug. Does not rekomenyodutsya to carry out continuous intravenous infusions - possibly formation of a deposit and adsorption of drug by polyvinyl chloride materials of infusional cylinders and tubes.

In the course of treatment by the patient the use of an etanoyol is strictly forbidden. Smoking weakens effect of drug.

At a renal/liver failure and prolonged treatment control of a picture of peripheral blood and "hepatic" enzymes is necessary.

The risk of formation of medicinal dependence increases during the using of high doses, the considerable duration of treatment, at the patients who were earlier abusing ethanol or medicines. Without special instructions it is not necessary to apply it is long.

The sharp termination of treatment because of risk of emergence of a sinyodrom of "cancellation" is not admissible (a headache, a mialgiya, uneasiness, tension, confusion of consciousness, irritability; in hard cases - a derealization, depersonalization, a hyperacusia, a photophobia, tactile hypersensitivity, paresthesias in konechyonost, a hallucination and epileptic seizures), however thanks to slow T1/2 of diazepam its manifestation is expressed much more weakly, than at other benzodiazepines.

At emergence at sick such unusual reactions as the increased aggression, acute conditions of excitement, uneasiness, sensation of fear, thoughts of suicide, a hallucination, strengthening of muscular spasms, difficult backfilling, a superficial dream, treatment it is necessary to stop.

Diazepam or its sharp cancellation at patients with epilepsy or with epileptic seizures in the anamnesis development of attacks or the epileptic status can accelerate an initiation of treatment.

During pregnancy apply only in exceptional cases and толь­ко according to "vital" indications. Has toxic effect on a fruit and uveliyochivat risk of development of inborn defects at use in the I trimester of a beremenyonost. Reception of therapeutic doses in later durations of gestation can priyovodit to physical dependence - the syndrome of "cancellation" at новорожденно­го is possible.

Children, especially at younger age, are very sensitive to the effect of benzodiazepines oppressing the central nervous system.

Use (especially intramusculary or intravenously) in doses is higher than 30 mg during 15 h before childbirth or at the time of delivery can cause at новорожденно­го respiratory depression (to an apnoea), decrease in a muscle tone, decrease in arteriyoalny pressure, a hypothermia, the weak act of suction (a syndrome of "the sluggish child") and disturbance of metabolism in response to a cold stress.

Influence on ability to manage vehicles and mechanisms. During treatment it is necessary to be careful during the driving of an avtoyotransport and occupation other potentially dangerous types of activity, treyobuyushchy the increased concentration of attention and speed of psychomotor reakyotion.

Side effects:

From a nervous system: in an initiation of treatment (especially at elderly bolyyony) - drowsiness, dizziness, increased fatigue, decrease in a sposobyonost to concentration of attention, an ataxy, a disorientation, instability of gait and bad coordination of movements, slackness, obtusion of emotions, delay of psikhicheyosky and motor reactions, an ecmnesia (develops more often, than at reception of other benzodiazepines); seldom - a headache, euphoria, a depression, a tremor, depression of mood, a katalepsy, confusion of consciousness, dystonic extrapyramidal reactions (the uncontrollable movements of a body, including eyes), weakness, a myasthenia during the day, a hyporeflexia, a dysarthtia; extremely seldom - parayodoksalny reactions (aggressive flashes, psychomotor arousing, fear, suicide bent, a muscular spasm, confusion of consciousness, a hallucination, acute excitement, irritability, uneasiness, sleeplessness).

From bodies of a hemopoiesis: leukopenia, neutropenia, agranulocytosis (fever, hyperthermia, pharyngalgia, excessive fatigue or weakness), anemia, thrombocytopenia.

From the alimentary system: dryness in a mouth or hypersalivation, "heartburn, a hiccups, a gastralgia, nausea, vomiting, a loss of appetite, locks; abnormal liver functions, increase in activity of "hepatic" transaminases and alkaline phosphatase, jaundice.

From cardiovascular system: heartbeat, tachycardia, sniyozheniye of arterial pressure.

From urinogenital system: urine incontience, ischuria, naruyosheny functions of kidneys, increase or decrease in a libido, dysmenorrhea.

Allergic reactions: skin rash, itch.

Influence on a fruit: teratogenecity (especially the I trimester), oppression of a tsentralyyony nervous system, breath disturbance, and suppression of a sucking reflex at newborns whose mothers used drug.

Local reactions: in an injection site - phlebitis or venous thrombosis (a krasnoyota, a swelling or pain in an injection site).

Others: accustoming, medicinal dependence; oppression of the dykhatelyyony center, dysfunction of external respiration, a vision disorder (diplopia), bulimia, decrease in body weight is rare.

At a sharp dose decline or the termination of reception - a syndrome of "cancellation" (irritability, a headache, uneasiness, nervousness, excitement, sensation of fear, nervousness, sleep disorders, a dysphoria, a spasm of unstriated muscles of internal oreganos and skeletal muscles, depersonalization, sweating strengthening, a deyopressiya, nausea, vomiting, a tremor, disorders of perception, including a hyperacusia, pareyosteziya, a photophobia, tachycardia, spasms, hallucinations, it is rare - acute psychosis).

At use in obstetrics - the full-term and premature children have a muscular hypotension, a hypothermia, диспноэ.

If any of the side effects specified in the instruction are aggravated, or you noticed any other side effects which are not specified in the instruction, a soyoobshchita about it to the doctor.

Interaction with other medicines:

Strengthens the oppressing action on the central nervous system of ethanol, sedative and antipsychotic medicines (neuroleptics), antidepressants, narcotic analgetics, medicines for the general anesteyoziya, muscle relaxants.

Inhibitors of a microsomal oxidation (including Cimetidinum, oral contraceptives, erythromycin, Disulfiramum, fluoxetine, an isoniazid, кетоконазол, метопролол, propranolol, the propoxyhair dryer, valproic acid) extend T1/2 and strengthen action.

Inductors of microsomal enzymes of a liver (rifampicin, carbamazepine, caffeine) reduce efficiency.

Narcotic analgetics increase euphoria, leading to increase of psiyokhichesky dependence.

Antiacid medicines reduce the speed of absorption of a diazeyopam from digestive tract, but not its completeness.

Hypotensive medicines can increase expressiveness of a sniyozheniye of arterial pressure.

Against the background of co-administration of clozapine strengthening of respiratory depression is possible.

At simultaneous use with low-polar cardiac glycosides increase in concentration of the last in blood serum and development of digitalis intoxication is possible (as a result of the competition for communication with proteins of plasma).

Reduces efficiency of a levodopa at patients with parkinsonism.

Omeprazol extends diazepam removal time.

Monoamine oxidase inhibitors, analeptics, psychostimulants - reduce activity.

Premedication diazepam allows to lower the fentanyl dose which is required for introduction general anesthesia and to reduce time necessary for "switching off" of consciousness by means of induction doses.

Can increase toxicity of a zidovudine.

Rifampicin can strengthen removal of diazepam and lower its kontsenyotration in plasma.

The theophylline (applied in low doses) can reduce or even to izvrayoshchat sedative action.

Pharmaceutical it is incompatible in one syringe or a dropper with other medicines.

Contraindications:

Hypersensitivity to diazepam, other components of drug and other benzodiazepines, a coma, shock, an acute drunkenness with oslableniyoy the vital functions, acute intoxications the medicines having the oppressing effect on the central nervous system (including naryokotichesky analgetics and somnolent medicines), acute diseases of a liver and kidneys, a heavy myasthenia, closed-angle glaucoma (a bad attack or predisposition); disturbance of breath and consciousness central proiskhozhdeyoniya; heavy HOBL (chronic obstructive pulmonary disease) (danger of a proyogressirovaniye of degree of respiratory insufficiency), acute respiratory insufficiency, a prostatauxe, pregnancy (especially I три­местр), the lactation period, children's age up to 30 days inclusive (at vnutrimyyoshechny and intravenous administration).

With care. Epilepsy and epileptic seizures in the anamnesis (an initiation of treatment diazepayomy or its sharp cancellation can accelerate development of attacks or эпилептическо­го the status), an absentia epileptica or Lennox-Gasto's syndrome (at intravenous administration promotes emergence of the tonic epileptic status), a liver and/or renal failure, a cerebral and spinal ataxy, hyperkinesias, medicinal dependence in the anamnesis, tendency to abuse of psikhoaktivyony medicines, organic diseases of a brain, a hypoproteinemia, night an apnoea (established or assumed), advanced age.

Overdose:

Symptoms: drowsiness, confusion of consciousness, paradoxical excitement, decrease in reflexes, an areflexia, an oglushennost, reduced reaction to pain stimulations, a deep sleep, a dysarthtia, an ataxy, a vision disorder (nystagmus), a tremor, bradycardia, an asthma or the complicated breath, an apnoea, the expressed weakness, a lowering of arterial pressure, a collapse, oppression of cordial and respiratory activity, a lump.

Treatment: gastric lavage, artificial diuresis, reception активированно­го coal. Symptomatic therapy (maintenance of breath and arterial davleyoniya); artificial ventilation of the lungs. As the specific antagonist isyopolzut flumazenit (in the conditions of a hospital). The hemodialysis is ineffective.

The antagonist of benzodiazepines flumazenit is not shown to patients with epilepsy, koyotory received treatment by benzodiazepines. At such patients antagonistic action in relation to benzodiazepines can provoke development of epiyoleptichesky attacks.

Storage conditions:

List No. 1 of strong substances PKKN. To store at a temperature not above 15 °C, in the place protected from light. To store in the places unavailable to children. A period of validity - 3 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Solution for intravenous and intramuscular administration of 5 mg/ml in ampuyola on 2 ml. Packaging: on 5 ampoules in a blister strip packaging; on 1 or 2 blister strip packagings with the application instruction in a pack from a cardboard. On 20, 50 or 100 blister strip packagings with 10, 25 or 50 application instructions respectively in a box from a cardboard or a box from a corrugated karyoton (for a hospital). Ampoule put knives or scarificators in a pack, a box or a box. When packaging ampoules with notches, rings or points of a break knives or skarifikayotor ampoule do not put.