Composition, form of production and packaging
The solution for intravenous and intravenous administration is transparent, from colorless to light green.
1 ml of 1 amp.
diazepam 5 mg 10 mg
[PRING] glycofurol, methylparahydroxybenzoate (nipagin), sodium metabisulphite, sodium citrate, propylene glycol, propyl parahydroxybenzoate (nipazole), ethanol 96%, water d / u.
2 ml - ampoules of dark glass (5) - plastic containers (1) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.
The description of the drug was approved by the manufacturer for the 2006 print edition.
PHARMACHOLOGIC EFFECT
Tranquilizer (anxiolytic), benzodiazepine derivative. Has a depressing effect on the central nervous system, which is realized mainly in the thalamus, hypothalamus and limbic system. Enhances the inhibitory effect of 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 compounding complex, leading to the activation of GABA receptors, which causes a decrease in the excitability of the subcortical structures of the brain, inhibition of polysynaptic spinal reflexes.
PHARMACOKINETICS
Suction and distribution
With the / m introduction, the 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%. Cmax in blood plasma are achieved in 0.5-1.5 h at v / m and within 0.25 h with iv injection. C ss are achieved in 1-2 weeks at constant reception.
Diazepam and its metabolites penetrate the BBB and placental barriers, are found in breast milk in concentrations corresponding to 1/10 of the concentrations in the plasma. Binding to plasma proteins - 98%.
Metabolism
Metabolised in the liver with the participation of isoenzymes CYP2C19, CYP3A4, CYP3A5 and CYP3A7 (98-99%) to pharmacologically active derivatives (N-desmethyldiazepam) and less active (temazepam and oxazepam).
Excretion
It is excreted by the kidneys - 70% (in the form of glucuronides), unchanged - 1-2% and less than 10% - with mildew. T 1/2 N-desmethyldiazepam 30-100 h, temazepam 9.5-12.4 h and oxazepam 5-15 h. With repeated use, the accumulation of diazepam and its active metabolites is significant. Refers to benzodiazepines with a long T 1/2 , excretion after cessation of treatment is slow, because metabolites persist in the blood for several days or even weeks.
Pharmacokinetics in special clinical cases
T 1/2 can 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).
INDICATIONS
- neurotic and neurosis-like disorders with anxiety;
- relief of psychomotor agitation associated with anxiety;
- relief of epileptic seizures and convulsive conditions of various etiologies;
- conditions accompanied by increased muscle tone (tetanus, with acute disorders of cerebral circulation);
- relief of withdrawal syndrome and delirium in alcoholism;
- premedication and ataralgesia in combination with analgesics and other neurotropic drugs for various diagnostic procedures, in surgical and obstetrical practice;
- in the clinic of internal diseases: in the complex therapy of hypertensive disease, (accompanied by anxiety, increased excitability), hypertensive crisis, vasospasms, climacteric and menstrual disorders.
DOSING MODE
To relieve psychomotor agitation associated with anxiety , Seduxen is prescribed for 10-20 mg IM or IV, if necessary, repeat the dose after 3-4 hours.
When tetanus is prescribed in / m, in / in jet or drip for 10-20 mg every 2-8 hours.
With epileptic status appoint in / m or iv in 10-20 mg, if necessary, repeat the dose in 3-4 hours.
To remove spasm of skeletal muscles , 10 mg IM is administered 1-2 hours before the operation.
In obstetrical practice appoint in / m for 10-20 mg with the opening of the cervix for 2-3 fingers.
Newborns are prescribed after 5 weeks of life (over 30 days) IV slowly 0.1-0.3 mg / kg body weight to a maximum dose of 5 mg, if necessary, repeat the injection after 2-4 hours (depending on the clinical symptomatology).
Children from 5 years of age and older should be administered IV slowly 1 mg every 2-5 minutes to a maximum dose of 10 mg; if necessary, the administration can be repeated after 2-4 hours.
SIDE EFFECT
From the side of the central nervous system and the peripheral nervous system: at the beginning of treatment (especially in elderly patients) - drowsiness, dizziness, fatigue, impaired concentration, ataxia, disorientation, gait instability and impaired coordination of movements, lethargy, dullness of emotions, slowing of mental and motor reactions , anterograde amnesia; rarely - headache, euphoria, depression, tremor, mood reduction, catalepsy, confusion, dystonic extrapyramidal reactions, asthenia, muscle weakness, hyporeflexia, dysarthria; extremely rarely - paradoxical reactions (aggressive outbreaks, psychomotor agitation, fear, suicidal tendencies, muscle spasms, confusion, hallucinations, anxiety, sleep disturbances).
On the part of the hematopoiesis system: leukopenia, neutropenia, agranulocytosis (manifested by chills, hyperthermia, sore throat, unusual fatigue or weakness), anemia, thrombocytopenia.
On the part of the digestive system: dry mouth, hypersalivation, heartburn, hiccough, gastralgia, nausea, vomiting, decreased appetite, constipation; violations of liver function, increased activity of hepatic transaminases and alkaline phosphatase, jaundice.
From the cardiovascular system: palpitation, tachycardia, lowering blood pressure.
On the part of the genitourinary system: urinary incontinence or retention, impaired renal function, increased or decreased libido, dysmenorrhea.
Allergic reactions: skin rash, itching.
Local reactions: at the injection site, phlebitis or venous thrombosis (redness, swelling, or pain at the injection site).
Other: addiction, drug dependence; rarely - depression of the respiratory center, impaired vision (diplopia), bulimia, weight loss.
With a sharp decrease in dose or discontinuation of reception, it is possible to develop withdrawal syndrome: increased irritability, headache, anxiety, fear, psychomotor agitation, sleep disturbances, dysphoria, spasm of smooth muscles of internal organs and skeletal muscles, depersonalization, sweating, depression, nausea, vomiting, tremor, perception disorders, incl. hyperaemia, paresthesia, photophobia, tachycardia, convulsions, hallucinations; rarely - psychotic disorders.
CONTRAINDICATIONS
- severe myasthenia gravis;
- coma;
- shock;
- an angle-closure glaucoma;
- the phenomenon of dependence in the anamnesis (including drug dependence and chronic alcoholism, except for the treatment of alcohol withdrawal syndrome and delirium);
- a syndrome of nocturnal apnea;
- a condition of alcoholic intoxication of a various degree of gravity;
- Acute intoxication with drugs that exert a depressing effect on the central nervous system (narcotic, hypnotics and psychotropic drugs);
- severe chronic obstructive pulmonary disease (risk of progression of respiratory failure);
acute respiratory failure;
- children's age up to 30 days inclusive;
- pregnancy (especially I and III trimester);
- lactation (breastfeeding);
- hypersensitivity to benzodiazepine derivatives.
PREGNANCY AND LACTATION
The drug should not be prescribed in the I and III trimesters of pregnancy.
If you need to use during pregnancy, you should carefully evaluate the intended benefit to the mother and the potential risk to the fetus and the baby.
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 CNS depression, respiratory failure, and suppression of the sucking reflex.
Use in doses above 30 mg for 15 hours before delivery or during childbirth may cause a respiratory depression in the newborn (up to apnea), a decrease in muscle tone, a decrease in blood pressure, hypothermia, a sluggish suckling syndrome in a newborn. Continuous use during pregnancy can lead to the formation of physical dependence and to the possible development of withdrawal symptoms in a newborn (muscular hypotension, hypothermia, dyspnea).
APPLICATION FOR FUNCTIONS OF THE LIVER
When prescribing the drug, patients with impaired renal function should carefully evaluate the risk-benefit ratio of therapy.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
When administering the drug, patients with impaired liver function should carefully evaluate the risk-benefit ratio of therapy.
APPLICATION FOR CHILDREN
Contraindication - children's age up to 30 days inclusive.
Children, especially at a young age, are very sensitive to the CNS depressing action of benzodiazepines.
The use of benzyl alcohol is not recommended for newborns. it is possible to develop a toxic syndrome manifested by metabolic acidosis, CNS depression, difficulty breathing, kidney failure, hypotension and possibly epileptic seizures, and intracranial hemorrhage.
APPLICATION IN ELDERLY PATIENTS
The drug is administered with caution to elderly patients.
SPECIAL INSTRUCTIONS
With caution, the drug is prescribed for absence (petit mal) or Lennox-Gastaut syndrome (with iv introduction may provoke the development of tonic epileptic status); epilepsy or epileptic seizures in the anamnesis (initiation of diazepam treatment or its abrupt withdrawal can accelerate the development of seizures or epileptic status), with hepatic and / or renal insufficiency, cerebral and spinal ataxia, hyperkinesia, propensity to abuse psychotropic drugs, organic brain diseases possible paradoxical reactions), hypoproteinemia, the elderly, with depression.
It is necessary to observe special care when administering diazepam in severe depression, the drug can be used to implement suicidal intentions.
An intravenous solution of diazepam should be administered slowly, into a large vein, for at least 1 minute for every 5 mg (1 ml) of the drug. It is not recommended to carry out continuous intravenous infusion, it is possible to form a precipitate and adsorb the preparation with polyvinyl chloride materials of infusion bottles and tubes.
The drug is not recommended to be prescribed for a long time.
The risk of forming drug dependence increases with the use of the drug in high doses, a significant duration of treatment, in patients who previously abused alcohol or drugs.
It is unacceptable to severely discontinue treatment because of the risk of withdrawal syndrome.
If such unusual reactions occur in patients, such as increased aggressiveness, psychomotor agitation, anxiety, fear, suicidal thoughts, hallucinations, increased muscle cramps, sleep disturbance, superficial sleep, the drug 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.
Elderly, Seduxen should be administered with extreme caution and the recommended dosage should not be exceeded.
When prescribing the drug, patients with impaired renal and hepatic function should carefully evaluate the risk-benefit ratio of therapy.
Contraindicated the introduction of Seduxen in the arterial channel because of the possible development of gangrene.
During treatment Seduxenom is prohibited from drinking alcohol.
Control of laboratory indicators
In renal / hepatic insufficiency or prolonged therapy, monitoring of peripheral blood pattern and activity of liver enzymes is necessary.
Use in Pediatrics
Children, especially at a young age, are very sensitive to the CNS depressing action of benzodiazepines.
The use of benzyl alcohol is not recommended for newborns. it is possible to develop a toxic syndrome manifested by metabolic acidosis, CNS depression, difficulty breathing, kidney failure, hypotension and possibly epileptic seizures, and intracranial hemorrhage.
Impact on the ability to drive vehicles and manage mechanisms
Against the background of Seduxen, patients are not recommended to engage in potentially dangerous activities that require increased attention and speed of psychomotor reactions.
OVERDOSE
Symptoms: drowsiness, oppression of consciousness of varying severity, paradoxical stimulation, decreased reflexes to areflexia, decreased reaction to painful stimuli, dysarthria, ataxia, nystagmus, tremor, bradycardia, severe weakness, decreased blood pressure, collapse, cardiac and respiratory depression (up to apnea ) activity, coma.
Treatment: gastric lavage, forced diuresis, activated charcoal. Symptomatic therapy (maintenance of breathing and blood pressure), ventilation. A specific antagonist, flumazenil, is used in a hospital setting. Hemodialysis is ineffective. The benzodiazepine antagonist flumazenil is not indicated by epilepsy patients who received benzodiazepine treatment. In such patients, antagonistic action against benzodiazepines may provoke the development of epileptic seizures.
DRUG INTERACTION
When combined with MAO inhibitors, strychnine and corazole, antagonism is possible with respect to the effects of Seduxen.
When combined with hypnotics and sedatives, opioid analgesics, other tranquilizers, benzodiazepine derivatives, muscle relaxants, general anesthetic agents, antidepressants, neuroleptics, ethanol, a dramatic increase in the inhibitory effect on the central nervous system is possible.
When used simultaneously with cimetidine, disulfiram, erythromycin, fluoxetine, as well as with oral contraceptives and estrogen-containing drugs that competitively inhibit liver metabolism (oxidation processes), it is possible to slow the metabolism of Seduxen and increase the concentration of diazepam in plasma.
When combined, isoniazid, ketoconazole and metoprolol slow the metabolism of diazepam and increase its concentration in the blood plasma.
When combined, propranolol and valproic acid increase the concentration of diazepam in the blood plasma.
When combined, rifampicin can increase the metabolism of diazepam and, as a result, reduce its concentration in the blood plasma.
When combined, inducers of microsomal liver enzymes reduce the effectiveness of diazepam.
Opioid analgesics increase the inhibitory effect of diazepam on the central nervous system.
With the simultaneous use of Seduxenom antihypertensives can increase the severity of blood pressure lowering.
When combined with clozapine, an increase in respiratory depression is possible.
With the simultaneous use of Seduxen 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).
When combined, Seduxen reduces the effectiveness of levodopa in patients with Parkinsonism.
Omeprazole prolongs diazepam clearance time.
MAO inhibitors, respiratory analeptics, psychostimulants when combined use reduce the activity of Seduxen.
When combined, a possible increase in zidovudine toxicity is possible.
Theophylline in low doses with simultaneous application can reduce the sedative effect of diazepam.
Premedication with diazepam reduces the dose of fentanyl required for an introductory general anesthesia, and shortens the time of onset of general anesthesia.
Pharmaceutical interaction
Seduxen's solution is pharmaceutically incompatible in one syringe with other drugs.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug belongs to the list of No. 1 potent substances of the Standing Committee on Drug Control of the Ministry of Health of the Russian Federation.
The drug should be stored in a place protected from light, inaccessible to children at a temperature of 8 В° to 15 В° C. Shelf life - 3 years.
