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

Excipients: propylene glycol 450.0 mg, ethanol 96% 100.0 mg, alcohol gasoline 15.0 mg, sodium benzoate 48.8 mg, acetic acid icic acid 2.3 mg, acetic acid 10% to pH approx. 6.3 - 6.4, water for injection up to 1 ml.

Ampoule 2 ml contains 10 mg of diazepam.

Description:

Transparent, colorless or yellow-green 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:

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. Possesses anxiolytic, sedative, hypnotic, myorelaxing and anticonvulsant. 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:

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%. The maximum concentrations in the blood plasma are achieved after 0.5-1.5 hours with intramuscular injection (further in / m) and within 0.25 h with intravenous (hereinafter in / in); 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. The connection with plasma proteins is 98%. Metabolised in the liver with the participation of the enzyme system CYP2C19, CYP3A4, CYP3A5 and CYP3A7 98 - 99% to pharmacologically very 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% - with calves. The half-life (T_1/2) desmethyldiazepam 30-100 h, temazepam - 9.5-12.4 h and oxazepam-5-15 h.

T_1/2may 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:

- 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. Apply for conditions accompanied by increased muscle tone (tetanus, with acute disorders of cerebral circulation, etc.);

- relief of withdrawal syndrome and delirium in alcoholism;

- It is also used 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 hypertension (accompanied by anxiety, increased excitability), hypertensive crisis, vasospasms, climacteric and menstrual disorders.

Contraindications:

Hypersensitivity to benzodiazepine derivatives, severe form of 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 with various degrees of severity, acute drug intoxication drugs that exert a depressing effect on the central nervous system (narcotic,hypnotics and psychotropic drugs), severe chronic obstructive pulmonary diseases (risk of progression of respiratory failure), acute respiratory failure, children up to 30 days inclusive, pregnancy (especially 1 and 3 trimester), the period of breastfeeding.

Carefully:Absence (petit mal) or Lennox-Gastaut syndrome (with intravenous administration, it can provoke the development of a 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), hepatic and / or renal failure, cerebral and spinal ataxia, hyperkinesis, a tendency to abuse psychotropic drugs, organic brain diseases (paradoxical reactions are possible), hypoproteinemia, elderly age, depression (see "Special instructions").

Dosing and Administration:

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

Condition of increased muscular tension and tetanus: dose for adults: first inject 10 mg in a slow intravenous injection or deep intramuscular (IM), and then intravenously drip 100 mg of diazepam in 500 ml of a 0.9% solution of sodium chloride or 5% glucose solution with speed of 5-15 mg per hour.

With epileptic status: appoint in / m or iv in 10-20 mg, if necessary, repeat the dose after 3-4 hours.

For premedication (removal of spasm of skeletal muscles): 10 mg IM every 1-2 hours before the operation.

In Obstetrics: appoint IM in 10-20 mg with the opening of the cervix for 2-3 fingers. Newborns appoint after 5-th week of life (over 30 days) in / slowly slowly at 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 clinical symptoms ).

Children from 5 years and older: I / O slowly 1 mg every 2-5 minutes to the maximum dose of 10 mg; if necessary, treatment can be repeated after 2-4 hours.

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 (develops more often than when taking other drugs)benzodiazepines); rarely - headache, euphoria, depression, 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 spasm, confusion, hallucinations, anxiety, sleep disturbances).

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

From the digestive system: dry mouth or hypersalivation, heartburn, hiccough, 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 (hereinafter referred to as blood pressure).

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), CNS depression, respiratory failure and suppression of sucking reflex in newborns whose mothers used the drug.

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 reduction in dose or discontinuation - syndrome "cancel" (irritability, headache, anxiety, fear, agitation, sleep disturbances, dysphoria, a spasm of smooth muscles of internal organs and skeletal muscles, depersonalization, increased sweating, depression, nausea, vomiting, tremor, disorders of perception, including hyperacusis, paresthesia, photophobia, tachycardia, convulsions, hallucinations, rare - psychotic disorders). When used in obstetrics - in newborns - muscular hypotension, hypothermia, dyspnea.

Overdose:

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

Treatment: gastric lavage, forced diuresis, activated charcoal. Symptomatic therapy (maintenance of breathing and blood 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:

When applying Relanium together with other drugs, the following interaction reactions can be observed:

- with monoamine oxidase inhibitors, strychnine and corazole - antagonism with respect to Relanium effects;

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

- 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 Relanium and increasing its plasma concentration;

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

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

- rifampicin can enhance the metabolism of Relanium 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;

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

- 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 (MAO), 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 of onset of general anesthesia.

Special instructions:

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 conduct continuous intravenous infusion - it is possible to form a precipitate and adsorption of the preparation with polyvinyl chloride materials of infusion cylinders and tubes.

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

The risk of forming drug dependence increases with the use of large doses, 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 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 diazepam treatment or its abrupt withdrawal in patients with epilepsy or epileptic seizures in an anamnesis can accelerate the development of seizures or epileptic status.

Has a toxic effect on the fetus and increases the risk of developing congenital malformations when used in the first trimester of pregnancy. Admission of therapeutic doses in later periods 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.

Children, especially at a young age, are very sensitive to the CNS depressing action of benzodiazepines. Newborns are not recommended to prescribe medications containing benzyl alcohol - possibly the development of a toxic syndrome manifested by metabolic acidosis, CNS depression, difficulty breathing, kidney failure, hypotension, and possibly epileptic seizures, and intracranial hemorrhage.

Use in doses above 30 mg for 15 hours before delivery or during labor may 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 (the so-called "sluggish child syndrome"). Older patients Relanium 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 pregnant women, as well as for patients with kidney and liver diseases.

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

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

When taking Relanium, patients are advised not to perform work that requires quick reaction and risk, for example, to drive vehicles and carry out other potentially hazardous activities.

During treatment Relanium is prohibited from drinking alcohol.

Form release / dosage:

Solution for intravenous and intramuscular injection 5 mg / ml.

Packaging:

By 2 ml in ampoules of colorless or orange glass for ampoules of the first hydrolytic class (Hept. F.). Above the point of fracture of the ampoule is a point of white or red color, and also a strip in the form of a ringlet of red color. 5 ampoules are placed in a PVC holder with a protective colorless PET film. One holder, or two holders, or ten holders in a cardboard box along with instructions for use.

Storage conditions:

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

Store at 15 ° C -25 ° C. Protect from light. Keep out of the reach of children.

Shelf life:

5 years.

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

Terms of leave from pharmacies:On prescription

Registration number:П N015758 / 01

Date of registration:29.05.2009

The owner of the registration certificate:Pharmaceutical factory "POLFARMA" JSCPharmaceutical factory "POLFARMA" JSC Poland

Manufacturer: & nbsp

POLPHARMA PHARMACEUTICAL WORKS, S.A. Poland

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp14.11.2013

Illustrated instructions

Instructions

Relanium® (Relanium®)