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

Excipients: Ethanol (ethyl alcohol) 95%, saturated with sodium chloride - 200 mg, propylene glycol - 200 mg, macrogol 400 (polyethylene oxide 400) - 200 mg, water for injection - up to 1 ml.

Description:Transparent colorless or with a yellowish-greenish tinge liquid.

Pharmacotherapeutic group:Anxiolytic agent (tranquilizer). 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:

The drug belongs to the list No. 1 of potent BACC substances.

Diazepam has a depressant effect on the central nervous system, which is realized mainly in the thalamus, hypothalamus and limbic system. Enhances the inhibitory effect of gamma-aminobutyric acid (GABA), which is one of the main mediators of pre- and postsynaptic inhibition of the transmission of nerve impulses to the central nervous system. It has anxiolytic, sedative, hypnotic, miorelaxing and anticonvulsant action. The mechanism of action of diazepam is due to the stimulation of the benzodiazepine receptors of supramolecular GABA-benzodiazepine-chloronophore receptor complex leading to activation of the GABA receptor, which causes a decrease in the excitability of the subcortical structures of the brain, inhibition of polysynaptic spinal reflexes.

Pharmacokinetics:

With intramuscular injection, absorption of diazepam can be slow and unstable (depends on the site of administration); when introduced into the deltoid muscle - absorption is rapid and complete. Bioavailability is 90%. Time,necessary to achieve the maximum concentration in blood plasma - 0.5-1.5 h with intramuscular injection and within 0.25 h with intravenous; equilibrium concentrations are achieved with constant intake after 1-2 weeks.

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. Connection with plasma proteins - 98 %.

Metabolized in the liver with the enzyme system CYP2C19, CYP3A4, CYP3A5 and CYP3A7. 98-99% to pharmacologically highly active derivatives (desmethyldiazepam) and less active (temazepam and oxazepam).

It is excreted by the kidneys - 70% (in the form of glucuronides), in unmodified form 1-2% and less than 10% - with calculous masses. The half-life of desmethyldiazepam is 30-100 h, the temazepam is 9.5-12.4 h and oxazepam is 5-15 h. The elimination half-life may be prolonged in newborns (up to 30 h), elderly and senile patients (up to 100 h) 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 a long half-life, elimination after cessation of treatment is slow,metabolites persist in the blood for several days or even weeks.

Indications:

- treatment of neurotic and neurosis-like disorders with anxiety;

- suppression of psychomotor agitation associated with anxiety;

- the arrest of epileptic seizures and convulsive conditions of various etiologies.

- states, accompanied by increased muscle tone (tetanus, acute disorders of cerebral circulation, etc.);

- relief of withdrawal syndrome and delirium in alcoholism;

- Premedication and ataralgesia in combination with analgesics under various diagnostic procedures, in surgical and obstetrical practice;

- in the clinic of internal diseases: in the complex therapy of hypertension (accompanied by anxiety, increased excitability), hypertensive crisis, vasospasms, climacteric and menstrual disorders.

Contraindications:

Hypersensitivity to benzodiazepine derivatives, severe myasthenia gravis, coma, shock, angle-closure glaucoma, addiction in history (drugs, alcohol, except for treatment of alcohol withdrawal syndrome and delirium), nighttime apnea syndrome, alcohol intoxication of varying severity, acute intoxication with drugs that exert a depressing effect on the central nervous system (narcotic, hypnotics and psychotropic drugs), severe chronic obstructive pulmonary diseases (danger of progression of respiratory failure), acute respiratory failure, children up to 30 days inclusive.

Carefully:

Absence (petit mal) or Lennox-Gastaut syndrome (when administered intravenously can trigger the development of tonic status epilepticus); epilepsy or epileptic seizures in the anamnesis (initiation of diazepam treatment or its abrupt withdrawal can accelerate the development of seizures or epileptic status), hepatic and / or renal failure, cerebral and spinal ataxia, hyperkinesis, a tendency to abuse psychotropic drugs, organic brain diseases (paradoxes are possible reactions), hypoproteinemia, elderly, children between the ages of 30 days, depression (see. "precautions").

Pregnancy and lactation:

The drug is contraindicated in the first trimester of pregnancy (increased risk of congenital malformations).In the second and third trimester of pregnancy, use is possible if the expected effect exceeds the potential risk to the fetus.

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

Use in doses above 30 mg for 15 hours before delivery or during labor 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).

During the treatment, the drug should stop breastfeeding.

Dosing and Administration:

Method of intramuscular and intravenous administration.

Treatment of neurotic and neurosis-like disorders with anxiety: the initial dose of 10 mg intramuscularly, in some cases with pronounced excitement, fear, the dose is increased to 20 mg.

Cessation of psychomotor agitation associated with anxiety, fear: the initial dose of 5-10 mg is administered slowly intravenously; dose can be repeated after 3-4 hours.

The states of increased muscle tone: adults are first introduced 10 mg in a slow intravenous injection or deeply intramuscularly, and then intravenously drip 100 mg of diazepam in 500 ml of a 0.9% solution of sodium chloride or 5 % solution of dextrose at a rate of 5-15 mg per hour. Children intramuscularly or intravenously: from 30 days to 5 years - 1-2 mg, children over 5 years - 5-10 mg; if necessary, the dose can be repeated after 3-4 hours.

Kupirovanie epileptic seizures and convulsions of different etiology: adults intramuscularly or intravenously for 10-20 mg, if necessary, repeat the dose after 3 to 4 hours. Children intravenously (slowly): from 30 days to 5 years - 0.2-0.5 mg every 2-5 minutes to a maximum dose of 5 mg, from 5 years and older - 1 mg every 2-5 minutes to a maximum dose of 10 mg; if necessary, treatment can be repeated after 2-4 hours.

Abstinence syndrome and delirium relief in case of alcoholism: on the first day - 10 mg intravenously or intramuscularly every 4-6 hours until a subjectively comfortable state or sleep occurs, in the following - a dose reduction to 5 mg 3-4 times a day.

Premedication: 1-2 hours prior to the beginning of the operation intramuscularly: adults - 10-20 mg; children - 0.1-0.2 mg / kg.

For short-term narcotic sleep with complex diagnostic (endoscopic) interventions: intravenously to adults - 10-20 mg, children - 0.1-0.2 mg / kg.

obstetrics and gynecology: intramuscularly 10-20 mg with the opening of the cervix for 2-3 fingers. With eclampsia: intravenously 10-20 mg per day, if necessary during a crisis - up to 70 mg per day.

In the clinic of internal diseases: intramuscularly at 5 mg per day, if necessary and taking into account the tolerability of the drug - up to 10 mg per day.

Patients of elderly and senile age: treatment should begin with half the usual dose for adults, gradually increasing it, depending on the effectiveness of therapy and the tolerability of the drug.

Usually after cupping the acute condition and achieving the necessary therapeutic effect, they switch to the appointment of diazepam in the form of tablets.

Side effects:

From the nervous system: at the beginning of treatment (especially in elderly patients) - drowsiness, dizziness, fatigue, impaired concentration, ataxia, disorientation, dulling of emotions, slowing of mental and motor reactions, anterograde amnesia; headache, euphoria, depression, tremor, catalepsy, confusion, dystonic extrapyramidal reactions (uncontrolled body movements), asthenia, muscle weakness, hyporeflexia, dysarthria,paradoxical reactions (aggressive outbreaks, psychomotor agitation, fear, suicidal tendencies, muscle spasm, confusion, hallucinations, anxiety, sleep disturbances).

On the part of the hematopoiesis system: leukopenia, neutropenia, agranulocytosis (chills, hyperthermia, sore throat, excessive fatigue or weakness), anemia, thrombocytopenia.

On the part of the digestive system: dry mouth or hypersalivation, heartburn, hiccups, gastralgia, nausea, vomiting, decreased appetite, constipation; violations of liver function, increased activity of "liver" transaminases and alkaline phosphatase, jaundice.

From the cardiovascular system: palpitation, tachycardia, lowering blood pressure.

From the genitourinary system: urinary incontinence or urinary retention, impaired renal function, increased or decreased libido, dysmenorrhea.

Allergic reactions: skin rash, itching.

Local reactions: with intravenous injection - phlebitis, venous thrombosis; when intramuscular injection - the formation of infiltrates.

With rapid intravenous administration - hypotension, orthostatic collapse, respiratory center depression, hiccups, impaired vision (diplopia).

Other: addiction, drug dependence, bulimia, weight loss.

If the dose is sharply reduced or discontinued: withdrawal syndrome (increased irritability, headache, anxiety, fear, psychomotor agitation, sleep disturbances, dysphoria, spasm of smooth muscles of the internal organs and skeletal muscles, depersonalization, increased sweating, depression, nausea, vomiting, tremor, perceptual disorders, in t Hyperacusis, paresthesia, photophobia, tachycardia, convulsions, hallucinations, psychotic disorders).

When used in obstetrics: in newborns - muscular hypotension, hypothermia, dyspnea.

Overdose:

Symptoms: drowsiness, oppression of consciousness of varying severity, paradoxical stimulation, decreased reflexes to areflexia, reduced reaction to painful stimulation, dysarthria, ataxia, visual impairment (nystagmus), tremor, bradycardia, lowering of arterial pressure, collapse, cardiac and respiratory depression (up to apnea ) activity, coma.

Treatment: forced diuresis. Symptomatic therapy (maintenance of breathing and arterial pressure), artificial ventilation. As a specific antagonist, flumazenil (in a hospital setting). The antagonist of benzodiazepines flumazenil It is not indicated for patients with epilepsy who were treated with benzodiazepines. In such patients, antagonistic action against benzodiazepines can trigger the development of epileptic seizures.

Hemodialysis is ineffective.

Interaction:

When diazepam is used in conjunction with other drugs, the following interaction reactions are observed:

- with monoamine oxidase inhibitors, strychnine and corazole - antagonism with respect to the effects of diazepam;

- with medicinal products having a depressing effect on the central nervous system (including hypnotics and sedatives, antipsychotics, narcotic analgesics, drugs for general anesthesia) - a sharp increase in the inhibitory effect on the central nervous system and respiratory center, pronounced arterial hypotension;

- with tricyclic antidepressants (incl. amitriptyline) - increased oppressive effect on the central nervous system, increased cholinergic action;

- with muscle relaxants - increased action of muscle relaxants, increased risk of apnea;

- with cimetidine, disulfiram, erythromycin, fluoxetine, as well as with oral contraceptives and estrogen-containing drugs that competitively inhibit liver metabolism (oxidation processes) - possibly slowing the metabolism of diazepam and increasing its plasma concentration;

- isoniazid, ketoconazole and metoprolol also slow down the metabolism of diazepam and increase its concentration in the blood plasma;

- propranolol and valproic acid increase the level of diazepam in blood plasma;

- rifampicin can enhance the metabolism of diazepam and, as a result, reduce its concentration in the blood plasma;

- inducers of microsomal liver enzymes - reduce efficacy;

- hypotensive drugs can increase the severity of lowering blood pressure;

- clozapine - possible increased respiratory depression;

- at simultaneous application with cardiac glycosides - it is possible to increase the concentration of the latter in the blood serum and the development of digitalis intoxication (as a result of competitive connection with plasma proteins);

- reduces the effectiveness of levodopa in patients with Parkinsonism;

- omeprazole prolongs diazepam clearance time;

- monoamine oxidase inhibitors, respiratory analeptics, psychostimulants - reduce the activity of the drug.

- potentially increased zidovudine toxicity;

- Theophylline (used in low doses) can reduce sedation.

Pharmaceutically incompatible in one syringe with other drugs.

Premedication with diazepam reduces the dose of fentanyl required for general anesthesia and reduces the time needed to "turn off" consciousness with induction doses.

Special instructions:

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

It is necessary to observe special care in the appointment of diazepam in severe depression, since the drug can be used to implement suicidal intentions.

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 unacceptable to severely discontinue treatment because of the risk of "withdrawal syndrome", but due to the slow half-life of diazepam, its manifestation is much weaker than in other benzodiazepines.

When patients develop such unusual reactions as increased aggressiveness, psychomotor agitation, anxiety, fear, suicidal thoughts, hallucinations, increased muscle cramps, difficult sleep, superficial sleep, treatment should be discontinued.

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

Intravenously, diazepam should be administered slowly, into a large vein for at least 1 minute for every 5 mg (1 ml) of the drug. The patient must be in lying position. After the introduction of the drug must be observed bed rest for at least 6 hours.

With the development of symptoms (see section "FROM caution "), an adequate allowance is needed in a hospital setting.

It is not recommended to carry out continuous intravenous infusions - sediment formation and adsorption of the preparation with polyvinylchloride materials of infusion bottles and tubes is possible.

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

Children, especially at a young age, are very sensitive to the depressing central nervous system by the action of benzodiazepines. Newborns are not recommended to prescribe medicines containing benzyl alcohol - it is possible to develop a fatal toxic syndrome manifested by metabolic acidosis, central nervous system depression, difficulty breathing, kidney failure, hypotension and possibly epileptic seizures, and intracranial hemorrhage.

Elderly patients Sibazon should be administered with extreme caution and do not exceed the recommended dose.

It is necessary to carefully evaluate the risk-benefit ratio for prescribing to patients with kidney and liver diseases.

Contraindicated introduction of Sibazone in the arterial channel because of the possible development of gangrene.

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

During the period of treatment, it is not allowed to drive vehicles and engage in potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Solution for intravenous and intramuscular injection 5 mg / ml.

Packaging:

2 ml per ampoule of neutral glass. For 10 ampoules, together with the instruction for use and the ampoule opening opener or ampoule scarifier, is placed in a cardboard box.

5 ampoules per circuit cell box made of polyvinyl chloride film and foil of aluminum printed lacquered or foil-free. 2 contoured cell packs together with instructions for use and a knife for opening ampoules or a scarifier ampullum are placed in a pack of cardboard.

When using ampoules with incisions, rings and break points, a scarifier ampoule or a knife for opening ampoules is not inserted.

Storage conditions:

List No. 1 of the strong BACC substances. In the dark place at a temperature of 5 to 20 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N003867 / 01

Date of registration:16.10.2009

The owner of the registration certificate:DALHIMFARM, OJSC DALHIMFARM, OJSC Russia

Manufacturer: & nbsp

DALHIMFARM, OJSC Russia

Information update date: & nbsp16.05.2012

Illustrated instructions

Instructions

Sibazon (Sibazon)