Sibazonum

General characteristics. Structure:

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

Excipients: lactoses monohydrate, potato starch, povidone (polyvinylpirrolidone low-molecular medical), stearate calcium monohydrate.

Pharmacological properties:

Pharmacodynamics. Diazepam - is derivative benzodiazepine, renders sedative and Yosnotvorny, anticonvulsant and central myorelaxation action. The mechanism of effect of diazepam is caused by stimulation of benzodiazepine retsepyotor supramolecular GAMK-benzodiazepin-hlorionofor a receptor komyopleks, 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 (limbic system, 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 reticular 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 is not removed.

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 is seldom observed.

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. After intake about 75% are soaked up. Klinicheyosky effects are shown in half an hour after administration of drug, and the maximum concentration (Cmax) in plasma is reached in 2 h, equilibrium concentration (Css) is reached at constant reception in 1-2 weeks. Diazepam works dliyotelny time during about 12 h. Bioavailability - 90%. Linkng with proteins of a blood plasma makes 94-99%, and at men is usually higher, than at women.

Diazepam and its metabolites get through hematoencephalic and playotsentarny barriers, sootvetyostvuyushchy 1/10 parts of concentration in plasma are found in breast milk in concentration. Communication with proteins of plasma - 98%.

It is metabolized in a liver with participation of isoenzymes of CYP2C19, CYP3A4, CYP3A5 and CYP3A7. 98-99% to pharmacological highly active derivative (desmetildiazepa) and less active (temazepam and oxazepam).

It is removed by kidneys - 70% (in the form of glucuronides), in not changed look - 1-2% and less than 10% - with a fecal masses. Removal has two-phase character: the initial phase of bystry and active distribution (T1/2 - 3 h) is followed by a proyodolzhitelny phase (T1/2 - 20-70 h). An elimination half-life (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 after the treatment termination - slow since metabolites remain in blood within several days or even weeks belongs to benzodiazepines with long T1/2.

Indications to use:

Appoint in quality:
- sedative at psychomotor excitement, in dermatologiyochesky practice at a pruritic dermatosis;

- anxiolytic means at acute alarming and phobic and treyovozhno-depressions, alcoholic psychoses with the abstinence phenomena;

- myorelaxation and an anticonvulsant at muscular spasms of the central origin at neurodegenerative zaboyolevaniye, including, at spine injuries, a lumbago, cervical radiculitis.

Preparation for operational interventions and diagnostic protseduyora.

Route of administration and doses:

Inside. The dose is calculated individually depending on a condition of the patient, a clinical picture of a disease, sensitivity of drug.

The adult appoint 5-15 mg a day usually for 2-3 receptions. In the conditions of a hospital patients can increase a daily therapeutic dose to 30 mg, and in case of a state aggravation, in need of and taking into account portability, to 60 mg.

Features of use:

Pregnancy and lactation. Use of medicine during pregnancy is allowed only in that sluyocha if use at mother has absolute indications, and use of safer, alternative means is impossible or it is contraindicated. Has toxic effect on a fruit and increases risk of development of vrozhyodenny defects at use in the I trimester of pregnancy. Reception of terapevticheyosky doses in later durations of gestation can lead to a physical zaviyosimost - the syndrome of "cancellation" at the newborn is possible. At use of Sibazonum in doses more than 30 mg during 15 h before childbirth or at the time of delivery respiratory depression (up to ап­ноэ) can cause in the newborn, decrease in a muscle tone, a lowering of arterial pressure, a hypothermia, the weak act of suction (a syndrome of the sluggish child). Drug is contraindicated in the period of a lactation.

The risk formation of medicinal dependence increases at use of high doses (more than 60 mg/days), the considerable duration of treatment, at the patsiyoent which were earlier abusing alcohol or medicines. Without special instructions it is not necessary to apply it is long.

It is not recommended to carry out monotherapy by benzodiazepines at an alarm combination to a depression (suicide attempts are possible). At emergence at sick paradoxical reactions, such as the increased aggression, acute soyostoyaniye of excitement, uneasiness, sensation of fear, thoughts of suicide, a gallyuyotsination, strengthening of muscular spasms, difficult backfilling, a superficial dream, diazepam should be cancelled. With care to appoint to patients with personal and behavioural disturbances. Paradoxical reactions are more often observed at deyoty and patients of senile age.

The bad attack of glaucoma is a contraindication to purpose of a diazeyopam.

Diazepam is capable to cause amnesia. Duration of amnesia zaviyosit from a dosage.

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 neobkhoyody control of a picture of peripheral blood and activity of "hepatic" feryoment.
The sharp termination of treatment because of risk of emergence of a sinyodrom of "cancellation" is not admissible (spasms, a tremor, spasms in a stomach and muscles, vomiting, perspiration), however thanks to slow T1/2 of diazepam its manifestation is expressed much more weakly, than at other benzodiazepines.

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.

When using a considerable dose of diazepam moderate aryoterialny hypotension develops. At patients with deep frustration of a cordial deyayotelnost considerable arterial hypotension, especially on the foyena of the expressed hypovolemia can develop.

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

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:

Classification of frequency of development of side effects (WHO): very often> 1/10, it is frequent from> 1/100 to <1/10, infrequently from> 1/1000 to <1/100, is rare from> 1/10000 to <1/1000, is very rare from <1/10000, including separate messages.

From system of a hemopoiesis: very seldom: a neutropenia (at prolonged use periodic control of composition of blood is recommended), a leukopenia, an agranulocytosis, anemia, thrombocytopenia.

From a nervous system: often: weakness, drowsiness, ataxy, infrequently: confusion of consciousness, depression, dysarthtia, rambling speech, decrease of the activity, decrease libido, headache, dizziness, tremor, memory disturbances, sleeplessness, hallucinations, uneasiness; seldom: a headache, euphoria, a depression, a tremor, depression of mood, a katalepsy, extrapyramidal reactions (the uncontrollable movements of a body, including eyes), a hyporeflexia; very seldom: paradoxical reactions (aggressive flashes, psychomotor excitement, fear, suicide bent, muscular spasm, irritability, acute excitement).

From cardiovascular system: infrequently: heart consciousness, bradycardia, faint, cardiovascular collapse.

From sense bodys: infrequently: sight illegibility, diplopia, nystagmus.

From the alimentary system: infrequently: lock, nausea, vomiting, dryness of a mucous membrane of an oral cavity or hypersalivation, heartburn, hiccups, gastralgia, loss of appetite; very seldom: jaundice (at prolonged use periodic control of function of a liver is recommended), abnormal liver functions, increase in activity of "hepatic" transaminases and an alkaline phosphatase.

From integuments: seldom: urticaria, skin rash, itch.

From a musculoskeletal system: infrequently: muscular weakness.

From an urinary system: infrequently: urine incontience, ischuria, renal failures.

From reproductive system: infrequently: disturbances of a menstrual cycle, increase or decrease in a libido.

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

In time and after therapy by diazepam small, clinically neznachiyomy changes on the electroencephalogram are possible (most often, nizkovoltazhny bystry activity).

At prolonged use of benzodiazepines portability of these drugs changes; signs of mental or physical dependence can develop. The risk of development of dependence is higher when using high doses and a long primeyoneniye of drugs.

At sharp phase-out of diazepam symptoms of a syndrome of "cancellation" develop (spasms, a tremor, spasms in a stomach and muscles, vomiting, perspiration). Most often these symptoms develop after prolonged use of high doses. Easier symptoms (a dysphoria, sleeplessness) are noted after sudden cancellation of the benzodiazepines which were accepted in therapeutic doses within several months.

Thus, it is necessary to avoid bystry drug withdrawal at its prolonged use, at the same time the daily dose has to decrease gradually.

At development of heavy adverse effects treatment has to be prekrashcheyono.

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, report 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), antideyopressant, narcotic analgetics, medicines for the general anesteyoziya, muscle relaxants.

Inhibitors of microsomal enzymes of a liver (including Cimetidinum, peroralyyony 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 diazepam from digestive tract, but not its completeness.

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

Against the background of simultaneous use of clozapine strengthening a breath ugneteyoniya is possible.

At simultaneous use with low-polar cardiac glycosides (digitoxin) increase in concentration of the last in blood serum and development of glikozidny 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.

Contraindications:

Hypersensitivity to diazepam, other components of drug and other benzodiazepines, a coma, shock, an acute drunkenness with oslableyoniy the vital functions, acute intoxications medicinal sredstvayom, having the oppressing effect on the central nervous system (including narcotic analgetics and somnolent medicines), acute diseases of a liver and kidneys, a heavy myasthenia, closed-angle glaucoma (acute при­ступ or predisposition); disturbance of breath and consciousness of the central origin; heavy HOBL (chronic obstructive pulmonary disease) (danger of progressing of respiratory insufficiency), acute respiratory insufficiency, heavy respiratory insufficiency, a heavy liver failure, gravis myasthenia, closed-angle glaucoma, a prostatauxe, deficit of lactase, a lactose intolerance, glyukozo-galaktozny malabsorption (drug contains lactose), children's age up to 6 years.

With care. Epilepsy or epileptic seizures in the anamnesis (an initiation of treatment diazeyopamy or its sharp cancellation development of attacks or the epilepticheyosky status can accelerate), a heavy depression (suicide attempts can be noted); a peyochenochny and/or renal failure, a cerebral and spinal ataxy, hyperkinesias, medicinal dependence in the anamnesis, tendency to a zloupotrebleyoniya psychoactive agents (including medicines), orgayonichesky diseases of a brain, psychosis (paradoxical reakyotion are possible), a hypoproteinemia, night an apnoea (established or assumed), pozhiyoly 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 treyomor, 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 who received treatment by benzodiazepines. At such patients antagonistic action in relation to benzodiazepines can provoke development of epiyoleptichesky attacks.

Storage conditions:

According to rules of storage of the psychotropic substances entered in the list III of "The list of the drugs, psychotropic substances and their precursors which are subject to control in the Russian Federation". In the place protected from light at a temperature not above 25 °C. To store in the places unavailable to children. A period of validity - 3 years. Not to apply after the term specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of 5 mg. Packaging: on 10 tablets in a blister strip packaging. 1, 2 or 5 blister strip packagings with the application instruction in a pack from a cardboard. On 100, 200, 400 blister strip packagings according to 5, 10, 20 application instructions in boxes from a cardboard or boxes from corrugated fibreboard (for a hospital).