Sibazon - instructions for use, dose, side effects, contraindications

Pharmacotherapeutic group:Anxiolytic agent (traquilizer). Psychotropic substance listed in List III of the "List of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation".

ATX: & nbsp

N.05.B.A.01 Diazepam

Pharmacodynamics:

Diazepam is a benzodiazepine derivative, has a sedative-hypnotic, anticonvulsant and central muscle relaxant effect. The mechanism of action of diazepam is due to the stimulation of the benzodiazepine receptors of the supramolecular GABA-benzodiazepine-chloronophore receptor complex, which leads to an increase in the inhibitory effect of GABA (gamma-aminobutyric acid - a mediator of pre- and postsynaptic inhibition in all parts of the central nervous system) on the transmission of nerve impulses. Stimulates benzodiazepine receptors located in the allosteric center of postsynaptic GABA receptors of the ascending activating reticular formation of the brain stem and intercalary neurons of the lateral horns of the spinal cord, reduces the excitability of the subcortical structures of the brain (limbic system, thalamus, hypothalamus), inhibits polysynaptic spinal reflexes.

Anxiolytic action is due to the influence on the amygdala complex of the limbic system and is manifested in a decrease in emotional tension, easing anxiety, fear, anxiety.

The sedative effect is due to the influence on the reticular formation of the brainstem and the nonspecific nuclei of the thalamus and is manifested by a decrease in the symptomatology of neurotic origin (anxiety, fear).

The main mechanism of hypnotic action is the inhibition of cells of the reticular formation of the brain stem.

Anticonvulsant action is realized by strengthening presynaptic inhibition. The spread of epileptogenic activity is suppressed, but the excited state of the focus is not removed.

Central miorelaksiruyuschee effect due to inhibition of the polysynaptic spinal afferent inhibitory pathways (to a lesser extent, monosynaptic). Perhaps a direct inhibition of the motor nerves and muscle functions.

Possessing moderate sympatholytic activity, can cause a decrease in blood pressure and an expansion of coronary vessels. Increases the threshold of pain sensitivity. It suppresses sympathoadrenal and parasympathetic (including vestibular) paroxysms. Reduces night secretion of gastric juice.

The effect of the drug is observed on the 2nd-7th day of treatment.

The productive symptomatology of psychotic genesis (acute delusional, hallucinatory, affective disorders) practically does not affect, rarely a decrease in affective tension, delusional disorders.

With abstinence syndrome with chronic alcoholism, weaken agitation, tremor, negativism, as well as alcoholic delirium and hallucinations.

Therapeutic effect in patients with cardialgia, arrhythmia and paresthesia is observed by the end of 1 week.

Pharmacokinetics:

Absorption is high. After ingestion, about 75% is absorbed. Clinical effects appear in half an hour after taking the drug, and the maximum concentration (C_m_Oh) in plasma is achieved after 2 hours, the equilibrium concentration (C_ss) is achieved with a constant intake after 1-2 weeks. Diazepam lasts for about 12 hours. Bioavailability is 90%. Binding to plasma proteins is 94-99%, and in men it is usually higher than in women.

Diazepam and its metabolites penetrate the blood-brain and placental barriers, are found in breast milk in concentrations corresponding to 1/10 of the plasma concentrations.The connection with plasma proteins is 98%.

Metabolized in the liver with the participation of isoenzymes CYP2C19, CYP3A4, CYP3A5 and CYP3A7. 98-99% to a pharmacologically active derivative (desmethyldiazepam) and less active (temazepam and oxazepam).

It is excreted by the kidneys - 70% (in the form of glucuronides), unchanged - 1 2% and less than 10% - with calves. The excretion has a two-phase character: behind the initial phase of rapid and active distribution (T_1/2 - 3 h) follows a prolonged phase (T_1/2 - 20-70 hours). The half-life (T_1/2) desmethyldiazepam - 30-100 h, temazepam - 9.5-12.4 h and oxazepam - 5-15 h.

T_1/2 may be prolonged in newborns (up to 30 hours), elderly and senile patients (up to 100 hours) and in patients with hepatic renal insufficiency (up to 4 days).

With repeated use, the accumulation of diazepam and its active metabolites is significant. Refers to benzodiazepines with long T_1/2, excretion after cessation of treatment is slow; metabolites persist in the blood for several days or even weeks.

Indications:

Assign as:

- sedative with psychomotor excitation, in dermatological practice with itching dermatoses;

- anxiolytic agent with acute anxiety-phobic and anxiety-depressive states, alcoholic psychoses with phenomena of abstinence;

- myorelaxing and anticonvulsant with muscular spasms of central origin in neurodegenerative diseases, including spinal cord injuries, lumbago, cervical radiculitis.

Preparation for surgical interventions and diagnostic procedures.

Contraindications:

Hypersensitivity to diazepam, other components of the drug and other benzodiazepines, coma, shock, acute alcohol intoxication with impaired vital functions, acute intoxication with drugs that have an inhibitory effect on the central nervous system (including narcotic analgesics and hypnotic drugs) , acute liver and kidney disease, severe myasthenia gravis, zakratougolnaya glaucoma (acute attack or predisposition); violation of breathing and consciousness of central origin; severe COPD (chronic obstructive pulmonary disease) (risk of progression of respiratory failure), acute respiratory failure, severe respiratory failure, severe hepatic impairment, myasthenia gravis gravis, closed-angle glaucoma, prostatic hypertrophy, lactase deficiency, lactose intolerance, glucose-galactose malabsorption (the drug contains lactose), children under 6 years.

Carefully:

Epilepsy or epileptic seizures in the anamnesis (initiation of diazepam treatment or its abrupt withdrawal can accelerate the development of seizures or epileptic status), severe depression (suicidal attempts may be noted); hepatic and / or renal insufficiency, cerebral and spinal ataxia, hyperkinesis, history of drug dependence, propensity to abuse of psychoactive substances (including drugs), organic brain diseases, psychosis (paradoxical reactions are possible), hypoproteinemia, nocturnal apnea (established or presumed), old age.

Pregnancy and lactation:

The use of the drug during pregnancy is allowed only if the use of the mother has absolute indications, and the use of a safer, alternative means is impossible or contraindicated.

Has a toxic effect on the fetus and increases the risk of developing congenital malformations when used in the first trimester of pregnancy. Taking therapeutic doses at a later time of pregnancy can lead to physical dependence - a syndrome of "cancellation" in a newborn is possible.

With the use of Sibazone in doses of more than 30 mg for 15 hours before delivery or during childbirth can cause a respiratory depression in the newborn (up to apnea), a decrease in muscle tone, a decrease in blood pressure, hypothermia, a weak act of sucking (sluggish child syndrome).

The drug is contraindicated during lactation.

Dosing and Administration:

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

Adults appoint 5-15 mg per day, usually for 2-3 hours. In a hospital setting, patients can increase the daily therapeutic dose to 30 mg, and In case of an exacerbation of a condition, if necessary and taking into account tolerability, up to 60 mg.

Side effects:

Classification of the incidence of adverse events (WHO):

very often> 1/10

often from> 1/100 to <1/10

infrequently from> 1/1000 to <1/100

rarely from> 1/10000 to <1/1000

very rarely from <1/10000, including individual messages.

On the part of the hematopoiesis system:

-very rare: neutropenia (with prolonged use, periodic monitoring of the blood composition is recommended), leukopenia, agranulocytosis, anemia, thrombocytopenia;

From the nervous system:

-frequently: weakness, drowsiness, ataxia,

-Sometimes: confusion, depression, dysarthria, incoherent speech, decreased activity, decreased libido, headache, dizziness, tremor, memory problems, insomnia, hallucinations, anxiety;

-only: headache, euphoria, depression, tremor, depression of mood, catalepsy, extrapyramidal reactions (uncontrolled body movements, including the eyes), hyporeflexia;

-very rare: paradoxical reactions (aggressive outbreaks, psychomotor agitation, fear, suicidal tendencies, muscle spasm, irritability, acute agitation);

From the cardiovascular system:

-nonly: heart palpitations, bradycardia, fainting, cardiovascular collapse;

From the sense organs:

-Often: blurred vision, diplopia, nystagmus;

From the digestive system:

-non-often: constipation, nausea, vomiting, dryness of the oral mucosa or hypersalivation, heartburn, hiccough, gastralgia, decreased appetite;

-very rare: jaundice (long-term use is recommended periodic monitoring of liver function), violations of liver function, increased activity of "liver" transaminases and alkaline phosphatase;

From the skin:

-only: urticaria, skin rash, itching;

From the musculoskeletal system:

-only: muscle weakness;

From the urinary system:

- Uncommon: urinary incontinence, urinary retention, impaired renal function;

On the part of the reproductive system:

-Often: violations of the menstrual cycle, increased or decreased libido.

Influence on the fetus: teratogenicity (especially I trimester), CNS depression, respiratory failure and suppression of the sucking reflex in newborns whose mothers used the drug.

During and after therapy with diazepam, small, clinically insignificant changes in the electroencephalogram (most often, low-speed fast activity) are possible.

With prolonged use of benzodiazepines, the tolerability of these drugs varies; may develop signs of mental or physical dependence.The risk of developing dependence is higher when using high doses and long-term use of drugs.

With a sharp discontinuation of diazepam, the symptoms of the "withdrawal" syndrome (convulsions, tremors, abdominal and muscle cramps, vomiting, sweating) develop. Most often these symptoms develop after prolonged use of high doses. More mild symptoms (dysphoria, insomnia) are noted after a sudden withdrawal of benzodiazepines taken at therapeutic doses for several months.

Thus, rapid discontinuation of the drug should be avoided with its long-term use, and the daily dose should be reduced gradually.

With the development of severe adverse effects, treatment should be discontinued.

If any of the side effects indicated in the instruction are aggravated, or you noticed any other side effects not listed in the instructions, inform the doctor about it.

Overdose:

Symptoms: drowsiness, confusion, paradoxical agitation, decreased reflexes, areflexia, deafness, decreased reaction to painful stimulation, deep sleep, dysarthria, ataxia, visual impairment (nystagmus), tremor, bradycardia,shortness of breath or shortness of breath, apnea, severe weakness, lowering of blood pressure, collapse, depression of cardiac and respiratory activity, coma.

Treatment: gastric lavage, forced diuresis, activated charcoal. Symptomatic therapy (maintenance of breathing and arterial pressure), artificial ventilation. As a specific antagonist, flumazenil (in a hospital setting). Hemodialysis is ineffective.

The antagonist of benzodiazepines flumazenil not shown epileptic patients who received treatment with benzodiazepines. In such patients, antagonistic action against benzodiazepines may provoke the development of epileptic seizures.

Interaction:

Strengthens the inhibitory effect on the central nervous system of ethanol, sedative and antipsychotic drugs (neuroleptics), antidepressants, narcotic analgesics, drugs for general anesthesia, muscle relaxants.

Inhibitors of microsomal liver enzymes (incl. cimetidine, oral contraceptives, erythromycin, disulfiram, fluoxetine, isoniazid, ketoconazole, metoprolol, propranolol, propoxyphene, valproic acid) extend T_1/2 and strengthen the action.

Inductors of microsomal liver enzymes (rifampicin, carbamazepine, caffeine) reduce the effectiveness.

The narcotic analgesics intensify euphoria, leading to an increase in mental dependence.

Antacids drugs reduce the rate of absorption of diazepam from the gastrointestinal tract, but not its complete.

Hypotensive drugs can increase the severity of lowering blood pressure.

Against the background of simultaneous application of clozapine, an increase in respiratory depression is possible.

When used simultaneously with low-polar cardiac glycosides (digitoxin) it is possible to increase the concentration of the latter in the serum and the development of glycosidic intoxication (as a result of competition for the connection with plasma proteins).

Reduces the effectiveness of levodopa in patients with Parkinsonism.

Omeprazole prolongs diazepam clearance time.

Inhibitors of monoamine oxidase, analeptics, psychostimulants - reduce activity.

Premedication with diazepam reduces the dose of fentanyl required for an introductory general anesthesia,necessary to "turn off" consciousness with the help of induction doses.

May increase the toxicity of zidovudine.

Rifampicin can increase the excretion of diazepam and lower its concentration in the plasma.

Theophylline (used in low doses) can reduce or even pervert the sedative effect.

Special instructions:

The risk of forming drug dependence increases with the use of high doses (more than 60 mg / day), a significant duration of treatment, in patients who previously abused alcohol or drugs. Without special instructions should not be used for a long time.

It is not recommended to use monotherapy with benzodiazepines when anxiety is combined with depression (suicidal attempts are possible). When paradoxical reactions occur in patients, such as increased aggressiveness, acute excitement, anxiety, fear, suicidal thoughts, hallucinations, increased muscle cramps, difficult falling asleep, shallow sleep,

diazepam should be discarded. With caution appoint patients with personal and behavioral disorders. Paradoxical reactions are more often observed in children and elderly patients.

An acute attack of glaucoma is a contraindication to the appointment of diazepam.

Diazepam is capable of causing amnesia. The duration of amnesia depends on the dosage.

In the process of treatment, patients are strictly prohibited from drinking ethanol. Smoking weakens the effect of the drug.

With renal / hepatic insufficiency and long-term treatment, control of the picture of peripheral blood and the activity of "liver" enzymes is necessary.

It is not permissible to abruptly stop treatment because of the risk of the "withdrawal" syndrome (convulsions, tremors, abdominal and muscle cramps, vomiting, sweating), but due to the slow T_1/2 diazepam, its expression is much weaker than that of other benzodiazepines.

The initiation of treatment with diazepam or its abrupt withdrawal in epileptic patients or with epileptic seizures in an anamnesis can accelerate the development of seizures or epileptic status.

When a significant dose of diazepam is used, moderate arterial hypotension develops. In patients with deep cardiac disorders, significant arterial hypotension may develop, especially in the presence of severe hypovolemia.

Children, especially at a young age, are very sensitive to the depressing central nervous system by the action of benzodiazepines.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets 5 mg.

Packaging:

10 tablets per contour cell pack. 1, 2 or 5 contour squares with instructions for use in a pack of cardboard. 100, 200, 400 contour mesh packages, respectively, with 5, 10, 20 instructions for use in cardboard boxes or corrugated cardboard boxes (for inpatient).

Storage conditions:

In accordance with the rules for storage of psychotropic substances listed in List III of the "List of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation".

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001270

Date of registration:30.08.2011

The owner of the registration certificate:MOSCOW ENDOCRINE FACTORY, FSUE MOSCOW ENDOCRINE FACTORY, FSUE Russia

Manufacturer: & nbsp

MOSCOW ENDOCRINE FACTORY, FSUE Russia

Information update date: & nbsp17.12.2014

Illustrated instructions

Instructions

Sibazon (Sibazon)