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

Composition:Each tablet contains as active substance - 0.0050 g of diazepam (sibazone); Excipients: lactose monohydrate (sugar milk), potato starch, calcium stearate (calcium stearic acid).

Description:Tablets are flat-cylindrical, white or white with a weak yellowish hue of color.

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:

Diazepam has a depressant effect on the central nervous system (CNS), 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 nerve impulse transmission in the central nervous system. It has anxiolytic, sedative, hypnotic, miorelaxing and anticonvulsant action.

The mechanism of action of diazepam is determined by the stimulation of the benzodiazepine receptors of the 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:

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) is achieved after 2 hours, equilibrium concentrations are achieved with a constant intake after 1-2 weeks. Diazepam lasts for about 12 hours. Bioavailability is 90%.The binding of diazepam to plasma proteins is 94-99%, and in men it is usually higher than that of women.

Diazepam and its metabolites penetrate the hematoencephalic barrier (BBB) and the placental barrier, are found in breast milk in concentrations corresponding to 1/10 of the plasma concentrations.

Metabolized in the liver 98-99% to pharmacologically active derivatives (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% - by the intestine. Excretion has a two-phase character: behind the initial phase of rapid and extensive distribution: the half-life (T_1/2) - 3 hours follows the prolonged phase T_1/2- 20-70 h. T_1/2desmethyldiazepam 30-100 h, temazepam-9.5-12.4 h and oxazepam-5-15 h.

T_1/2can be prolonged in newborns (up to 30 hours), elderly and senile patients (up to 100 hours) and in patients with hepatic renal failure (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, because metabolites persist in the blood for several days or even weeks.

Indications:

Treatment of neurotic and neurosis-like disorders with anxiety.

It is used for spastic conditions associated with the defeat of the brain or spinal cord (cerebral palsy, athetosis, tetanus).

An abstinent alcoholic syndrome (in complex therapy).

It is also used for premedication and ataralgesia in combination with analgesics and other neurotropic drugs for various diagnostic procedures, in surgical 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.

In dermatological practice it is used for itching dermatoses.

Contraindications:

Hypersensitivity to benzodiazepine derivatives, severe myasthenia gravis, coma, shock, occlusive glaucoma (acute attack or predisposition), nighttime apnea syndrome, alcohol intoxication of various severity, acute intoxication with drugs that exert a depressing effect on the central nervous system (narcotic, hypnotics and psychotropic facilities),severe chronic obstructive pulmonary diseases (risk of progression of respiratory failure), acute respiratory failure, children under 7 years of age, pregnancy (especially I and III trimester), the period of breastfeeding.

Due to the presence of lactose, patients with rare hereditary diseases, such as lactose tolerance, lactase deficiency or glucose-galactose malabsorption, should not take the drug.

Carefully:Epilepsy or epileptic seizures in the anamnesis (initiation of treatment with diazepam or its abrupt withdrawal may accelerate the development of seizures or epileptic status), history of drug dependence, hepatic and / or renal failure, cerebral and spinal ataxia, hyperkinesis, propensity to abuse psychotropic drugs, organic diseases the brain (possible paradoxical reactions), hypoproteinemia, elderly age.

Dosing and Administration:

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

When administered orally, the average single dose for adults is 5-15 mg. In some cases, with pronounced excitement, fear, anxiety, it can be increased to 20 mg. The daily dose is usually 15-45 mg, the maximum daily - 60 mg. The daily dose of the drug is divided into 2-3 doses.

Average recommended doses for different conditions:

As an anxiolytic is prescribed by mouth, 5-10 mg 2-4 times a day.

With alcohol withdrawal syndrome - 10 mg 3-4 times a day in the first 24 hours, followed by a decrease to 5 mg 3-4 times a day.

Older patients and weakened patients receive the drug at lower doses, which are 1/2 or 2/3 of the average.

Neurology: spastic conditions of central origin in degenerative neurological diseases - inside, 5-10 mg 2-3 times a day.

In the clinic of internal diseases, 5 mg 2-3 times a day, if necessary and taking into account the tolerance to 10 mg 4 times a day.

Menopausal and menstrual disorders - 5 mg 2-3 times a day.

Anaesthesiology, surgery: premedication - on the eve of surgery, in the evening - 10-20 mg inside. Pediatrics: appoint with a gradual increase in dose (starting with low doses and slowly increasing them to the optimal dose, well tolerated by the patient),daily dose (can be divided into 2-3 doses, with the main, the largest dose, taken in the evening): inside, from 7 years and older - 5 mg. The maximum daily dose is 10 mg.

Side effects:

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

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

From 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: heartbeat, tachycardia, decrease blood pressure (BP).

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

Allergic reactions: skin rash, itching.

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.

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

Other: addiction, drug dependence; rarely - depression of the respiratory center, impaired vision (diplopia), bulimia, weight loss.

With a sharp reduction in dose or discontinuation of reception - withdrawal syndrome (increased irritability, headache, anxiety, fear, psychomotor agitation, sleep disturbance,dysphoria, spasm of smooth muscles of internal organs and skeletal muscles, depersonalization, increased sweating, depression, nausea, vomiting, tremor, perception disorders, incl. hyperaemia, paresthesia, photophobia, tachycardia, convulsions, hallucinations, rarely - psychotic disorders).

Overdose:

Symptoms: drowsiness, depression 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 blood pressure, collapse, cardiac and respiratory depression (up to apnea) activity, coma.

Treatment: forced diuresis, symptomatic therapy (maintenance of breathing and blood pressure), artificial ventilation of lungs, gastric lavage, reception of activated charcoal. 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:

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

monoamine oxidase inhibitors (MAO), analeptics, psychostimulants - reduce the activity of diazepam;

with hypnotics, sedatives, other tranquilizers, benzodiazepine derivatives, muscle relaxants, general anesthetic agents, antidepressants, neuroleptics, alcohol - a sharp increase in the oppressive effect on the central nervous system;

narcotic analgesics increase euphoria, leading to an increase in psychological dependence;

inhibitors of microsomal oxidation (incl. cimetidine, oral contraceptives, erythromycin, disulfiram, fluoxetine, isoniazid, ketoconazole, metoprolol, propranol, propoxyphene, valproic acid) extend T_1/2and enhance the action of diazepam;

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. Narcotic analgesics increase the inhibitory effect on the central nervous system.

Hypotensive drugs can increase the severity of blood pressure lowering.

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

Clozapine - may increase respiratory depression.

When applied simultaneously with cardiac glycosides - may increase the concentration of the latter in the serum, and the development of digitalis intoxication (due to the concurrent connection with plasma proteins).

Reduces the effectiveness of levodopa in patients with Parkinsonism.

Omeprazole prolongs diazepam clearance time.

Psychostimulants - reduce the activity of the drug.

It is possible to increase the toxicity of zidovudine.

Theophylline (used in low doses) can reduce sedation. Premedication with diazepam reduces the dose of fentanyl required for an introductory general anesthesia, and shortens the time of onset of general anesthesia.

Special instructions:

The purpose of the drug should be accompanied by careful monitoring of its use. In renal / hepatic failure and prolonged treatment is necessary to monitor the pattern of peripheral blood and "liver" enzymes.

The risk of forming drug dependence increases with the use of large doses,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 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.

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

Children, especially at a young age, are very sensitive to the CNS depressing action of benzodiazepines. 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 cause depression of the fetal CNS.Continuous use during pregnancy can lead to physical dependence - possible withdrawal symptoms in a newborn.

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 (BP), hypothermia, a weak act of sucking (the so-called "sluggish child syndrome ").

Elderly patients diazepam 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.

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

During the period of treatment, it is necessary to refrain from driving and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

During treatment with diazepam, alcohol is prohibited.

Form release / dosage:

Tablets of 5 mg.

Packaging:

10 tablets per contour cell pack. For 20 tablets in cans of light-protective glass or polymeric. Bank or 2 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

List III of the list of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation.

Store in a dark place at a temperature of no higher than 30 ° C. Keep out of the reach of children.

Shelf life:

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

Terms of leave from pharmacies:On prescription

Registration number:LS-000931

Date of registration:28.05.2010

The owner of the registration certificate:ORGANICS, JSC ORGANICS, JSC Russia

Manufacturer: & nbsp

ORGANICS, JSC Russia

Information update date: & nbsp18.10.2013

Illustrated instructions

Instructions

Sibazon (Sibazon)