Composition, form of production and packaging
The solution for intravenous and / or injection is clear, colorless or yellow-green in color.
1 ml of 1 amp.
diazepam 5 mg 10 mg
[PRING] propylene glycol, ethanol 96%, benzyl alcohol, sodium benzoate, acetic acid glacial, acetic acid 10% (to pH 6.3-6.4), water d / u.
2 ml - ampoules (5) - plastic holders (1) - packs cardboard.
2 ml - ampoules (5) - holders plastic (2) - packs cardboard.
2 ml - ampoules (5) - holders plastic (10) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
PHARMACHOLOGIC EFFECT
Anxiolytic drug (tranquilizer), benzodiazepine derivative.
Diazepam has an inhibitory 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 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, which leads 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
Suction
After the / m administration, diazepam is absorbed slowly and unevenly, depending on the site of administration; when introduced into the deltoid muscle, absorption is rapid and complete. Bioavailability is 90%. C max at the / m introduction is achieved through 0.5-1.5 h, with the / in the introduction for 0.25 h.
Distribution
With a constant use of C ss are achieved in 1-2 weeks.
Binding to plasma proteins is 98%.
Diazepam and its metabolites penetrate the BBB and placental barrier, are excreted in breast milk in concentrations corresponding to 1/10 of the concentration in the blood plasma.
With repeated use of the drug, a pronounced cumulation of diazepam and its active metabolites is observed.
Metabolism
Metabolised in the liver with the participation of isoenzymes CYP2C19, CYP3A4, CYP3A5 and CYP3A7 to 98-99% with the formation of a very active metabolite of desmethyldiazepam and less active metabolites of temazepam and oxazepam.
Excretion
T 1/2 desmethyldiazepam is 30-100 h, temazepam - 9.5-12.4 h and oxazepam - 5-15 h.
It is excreted by the kidneys - 70% (in the form of glucuronides), unchanged - 1-2%, and less than 10% - with feces.
Refers to benzodiazepines with long T 1/2 . After discontinuation of treatment, metabolites persist in the blood for several days or even weeks.
Pharmacokinetics in special clinical cases
T 1/2 can increase in newborns - up to 30 hours, in elderly patients - up to 100 hours, in patients with hepatic and renal insufficiency - up to 4 days.
INDICATIONS
- treatment of 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 (including tetanus, acute disorders of cerebral circulation);
- relief of withdrawal syndrome and delirium in alcoholism;
- for 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 arterial hypertension (accompanied by anxiety, increased excitability), hypertensive crisis, vasospasms, climacteric and menstrual disorders.
DOSING MODE
With a view to stopping the psychomotor agitation associated with anxiety, prescribe 5-10 mg IV slowly, if necessary, 3-4 hours later, the drug is administered again in the same dose.
When tetanus is prescribed for 10 mg IV slowly or deeply / m, then intravenously injected 100 mg of diazepam in 500 ml of a 0.9% solution of sodium chloride or 5% glucose solution at a rate of 5-15 mg / h.
With epileptic status , I / m or IV is prescribed for 10-20 mg, if necessary, 3-4 hours later, the drug is given again in the same dose.
To relieve spasm of skeletal muscles - 10 mg IM for 1-2 hours before the operation.
In midwifery appoint in / m for 10-20 mg with the opening of the cervix for 2-3 fingers.
Newborns after 5 th week of life (over 30 days) are prescribed IV slowly 100-300 Ојg / kg body weight to the maximum dose of 5 mg, if necessary, the administration is repeated after 2-4 hours (depending on the clinical symptoms).
Children aged 5 years and older receive I / O 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 central nervous system and peripheral 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 (develops more often, than when taking other benzodiazepines); rarely - headache, euphoria, depression, tremor, catalepsy, confusion, dystonic extrapyramidal reactions (uncontrolled movements), asthenia, muscle weakness, hyporeflexia, dysarthria; in some cases, paradoxical reactions (outbreaks of aggression, 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, fatigue or weakness), anemia, thrombocytopenia.
On the part of the digestive system: dry mouth or hypersalivation, heartburn, hiccough, gastralgia, nausea, vomiting, decreased appetite, constipation, impaired liver function, increased activity of hepatic transaminases and alkaline phosphatase, jaundice.
From the cardiovascular system: arterial hypotension, tachycardia.
From the urinary system: urinary incontinence or retention, impaired renal function.
On the part of the reproductive system: increased or decreased libido, dysmenorrhea.
On the part of the respiratory system: respiratory depression (with too rapid administration of the drug).
Allergic reactions: skin rash, itching.
Local reactions: phlebitis or venous thrombosis (redness, swelling, 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 - withdrawal syndrome (increased irritability, headache, anxiety, fear, psychomotor agitation, sleep disturbances, dysphoria, spasm of smooth muscles of the internal organs and skeletal muscles, depersonalization, sweating, depression, nausea, vomiting, tremor , perceptual disorders, including hyperacusia, paresthesia, photophobia, tachycardia, convulsions, hallucinations, rarely - psychotic disorders). When used in obstetrics in newborns - muscle hypotension, hypothermia, dyspnea.
CONTRAINDICATIONS
- severe myasthenia gravis;
- coma;
- shock;
- an angle-closure glaucoma;
- indication in the history of the phenomenon of dependence on narcotic drugs, alcohol (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 trimesters);
- lactation period (breastfeeding);
- Hypersensitivity to benzodiazepines.
Precautions should be taken with petit mal or Lennox-Gastaut syndrome (with an iv administration can trigger 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 status epilepticus) , hepatic and / or renal insufficiency, cerebral and spinal ataxia, hyperkinesis, propensity to abuse of psychotropic drugs, depression, organic brain diseases (possible us paradoxical reactions) for hypoproteinemia, elderly patients.
PREGNANCY AND LACTATION
The drug is contraindicated for use in pregnancy and lactation.
Relanium В® has a toxic effect on the fetus and increases the risk of congenital malformations when used in the first trimester of pregnancy. Taking the drug in therapeutic doses at a later time of pregnancy can cause oppression of the fetal CNS. Continuous use during pregnancy can lead to physical dependence - there may be withdrawal symptoms in a newborn.
When using Relanium 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").
APPLICATION FOR FUNCTIONS OF THE LIVER
If it is necessary to use the drug in patients with kidney disease, the risk-benefit ratio of therapy should be assessed.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
If it is necessary to use the drug in patients with liver diseases, the risk-benefit ratio of therapy should be assessed.
APPLICATION FOR CHILDREN
Newborns after 5 th week of life (over 30 days) are prescribed IV slowly 100-300 Ојg / kg body weight to the maximum dose of 5 mg, if necessary, the administration is repeated after 2-4 hours (depending on the clinical symptoms).
Children aged 5 years and older receive I / O 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.
APPLICATION IN ELDERLY PATIENTS
With caution appoint elderly patients.
SPECIAL INSTRUCTIONS
With extreme caution, diazepam should be given in severe depression, because the drug can be used to implement suicidal intentions.
The / in solution of Relanium should be administered slowly, into a large vein, at least for 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 adsorption of the preparation with materials from PVC infusion bottles and tubes.
In renal or hepatic insufficiency and long-term use, it is necessary to control the picture of peripheral blood and the activity of hepatic enzymes.
The risk of forming drug dependence increases with the use of Relanium in high doses, with a significant duration of treatment in patients who previously abused alcohol or drugs. Without special need, the drug should not be used for a long time. It is unacceptable to severely discontinue treatment because of the risk of withdrawal, but due to the slow elimination of diazepam, the manifestation of this syndrome 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 beginning of treatment with Relanium or its abrupt reversal in patients with epilepsy or with epileptic seizures in an anamnesis can accelerate the development of seizures or epileptic status.
With extreme caution and not exceeding the recommended dose, Relanium В® should be used in elderly patients.
If it is necessary to use the drug in patients with liver and kidney disease, the risk-benefit ratio of therapy should be assessed.
Relanium В® is not administered intraarterially because of the risk of developing gangrene.
With prolonged use of the drug, it is possible to develop addiction.
During the period of treatment, alcohol consumption is prohibited.
Use in Pediatrics
Children, especially young children, are very sensitive to the depressing effect of benzodiazepines on the central nervous system.
The use of benzyl alcohol is not recommended for newborns. possibly the development of a toxic syndrome manifested by metabolic acidosis, CNS depression, difficulty breathing, kidney failure, arterial hypotension and, possibly, epileptic seizures, as well as intracranial hemorrhage.
Impact on the ability to drive vehicles and manage mechanisms
Patients receiving the drug should refrain from engaging in potentially dangerous activities that require increased attention and speed of psychomotor reactions.
OVERDOSE
Symptoms: drowsiness, oppression of consciousness of varying severity, paradoxical stimulation, reduced reflexes to areflexia, reduced reaction to painful stimuli, dysarthria, ataxia, visual disturbances (nystagmus), tremor, bradycardia, lowering of blood pressure, collapse, cardiac depression, respiratory depression, coma.
Treatment: gastric lavage, forced diuresis, activated charcoal; conducting symptomatic therapy (maintaining breathing and BP), ventilation.
Hemodialysis is ineffective.
A specific antidote is flumazenil, which should be used in hospital settings. Flumazenil is not indicated in patients with epilepsy who received treatment with benzodiazepines. In such cases, antagonistic action with respect to benzodiazepines may provoke the development of epileptic seizures.
DRUG INTERACTION
MAO inhibitors, strychnine and corazole are antagonistic to the effects of Relanium.
With the simultaneous use of Relanium with hypnotics, sedatives, opioid analgesics, other tranquilizers, benzodiazepine derivatives, muscle relaxants, general anesthetic agents, antidepressants, neuroleptics, and also with ethanol, there is a dramatic increase in the inhibitory effect on the CNS.
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 diazepam and increase its concentration in the blood plasma.
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 concentration of diazepam in the blood plasma.
Rifampicin can induce the metabolism of diazepam, which leads to a decrease in its concentration in the blood plasma.
Inductors of microsomal liver enzymes reduce the effectiveness of Relanium.
Opioid analgesics increase the inhibitory effect of Relanium on the CNS.
With simultaneous use with antihypertensive drugs, it is possible to intensify the hypotensive effect.
With simultaneous application with clozapine, an increase in respiratory depression is possible.
With the simultaneous use of Relanium 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 competition with plasma proteins).
Relanium reduces the effectiveness of levodopa in patients with Parkinsonism.
Omeprazole prolongs diazepam clearance time.
Respiratory analeptics, psychostimulants reduce the activity of Relanium.
With simultaneous application with Relanium, zidovudine toxicity can be increased.
Theophylline (in low doses) can reduce the sedation effect of Relanium.
Premedication Relanium allows to reduce the dose of fentanyl required for an introductory general anesthesia, and shortens the time of onset of general anesthesia.
Pharmaceutical interaction
Relanium В® is incompatible in one syringe with other drugs.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
Relanium В® belongs to the list of the strongest substances of the Standing Committee on Drug Control of the Ministry of Health of the Russian Federation.
The drug should be stored out of reach of children, protected from light at a temperature of 15 В° to 25 В° C. Shelf life - 5 years.
