Relium - instructions for use, doses, side effects, contraindications

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 belongs to the group of benzodiazepine derivatives.

Diazepam has a depressant effect on the central nervous system (CNS), which is realized mainly in the thalamus, hypothalamus and limbic system. Increases 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 in the central nervous system. Diazepam has an anxiolytic, sedative, hypnotic, central miorelaxing and anticonvulsant action. The mechanism of action of the drug is determined by the stimulation of the benzodiazepine receptors of supramolecular GABA-benzodiazepine-chloronophore compounding 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:

Suction

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 concentration in blood plasma is achieved after 0.5-1.5 hours with intramuscular injection (further in / m) and within 0.25 hours with intravenous administration (hereinafter in / in). Equilibrium concentration is achieved with constant administration after 1 -2 weeks.

Distribution

Diazepam passes through the blood-brain and placental barriers. Penetrates into breast milk. Approximately 98% is associated with blood proteins. The degree of binding to proteins in newborns and in patients with liver failure is reduced. Especially high concentrations diazepam reaches the cerebral cortex, cerebellum, midbrain and spinal cord. The drug shows a great affinity for adipose tissue, in which it is deposited and then gradually released into the blood. Repeated administration of the drug may lead to cumulation of the drug and its metabolites (may persist in the blood for several days or even weeks).

Metabolism

Diazepam is metabolized in the liver with the formation of active metabolites: N-desidmethyldiazepam (Nordazepam) and N-methyloxazepam. Both metabolites undergo transformation into pharmacologically active oxazepam, which binds to glucuronic acid.

Excretion

The half-life period is 24-48 hours and can be prolonged in patients in advanced age, in children and in patients with hepatic impairment. Active metabolites prolong the half-life. The drug is excreted mainly with urine in the form of metabolites (about 70%), some are excreted unchanged (can reach 25%) and less than 10% is excreted by the feces.

Indications:

Treatment of neurotic and neurosis-like disorders with anxiety. Suppression of psychomotor agitation associated with anxiety.

Cessation of epileptic seizures and convulsions of various etiologies. Apply for conditions accompanied by increased muscle tone (tetanus, with acute disorders of cerebral circulation, etc.).

Cessation 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 practice.

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

Contraindications:

Individual intolerance to benzodiazepine derivatives, respiratory depression of central origin and expressed respiratory failure regardless of cause, impaired consciousness, glaucoma, myasthenia gravis, pregnancy (especially I trimester) and breastfeeding, depressive states with suicidal tendencies, shock, coma, head trauma, acute alcoholic intoxication with impaired vital functions, acute intoxication with drugs that exert a depressing effect on the central nervous system (narcotic, sleep open and psychotropic agents), absence or Lennox-Gastaut syndrome (with intravenous administration contributes to the development of tonic epileptic status), children up to 5 weeks.

If you have one of the listed conditions and / or diseases before taking the drug, be sure to consult a doctor.

Carefully:

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 insufficiency,cerebral and spinal ataxia, hyperkinesis, history of addiction, organic brain diseases, psychosis (possible paradoxical reactions), hypoproteinemia, nocturnal apnea (established or presumed), advanced age.

If you have one of the listed conditions and / or diseases before taking the drug, be sure to consult a doctor.

Pregnancy and lactation:

During pregnancy are used only in exceptional cases and only for "vital" indications. The drug 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 central nervous system of the newborn. Continuous use during pregnancy can lead to physical dependence - there may be withdrawal symptoms in a newborn.

When treating diazepam, you should not breast-feed.

Dosing and Administration:

Dosing regimen and duration of treatment, depending on the condition and reaction of the patient - strictly according to the doctor's prescription.

Adults

Duplication of psychomotor agitation associated with anxiety is prescribed for 5-10 mg intramuscularly (IM) or intravenously (IV), if necessary, repeat the dose 3-4 hours later.

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.

For the removal of spasm of skeletal muscles - 10 mg IM for 1-2 hours before the operation.

In acute alcohol withdrawal syndrome: first 10 mg intramuscularly or intravenously, then 5-10 mg after 3-4 hours.

For premedication: 0.1-0.2 mg / kg body weight

In the complex therapy of hypertension (accompanied by anxiety, increased excitability), hypertensive crisis, vasospasms,

menopausal and menstrual disorders: the dose, the frequency of administration and the course of treatment are selected individually, with an average single dose of 5-10 mg.

Children

Newborns are prescribed after the 5th week of life (older than 30 days) IV slowly over 0D-0.3 mg / kg body weight to the maximum dose of 5 mg, if necessary, repeat the injection after 2-4 hours (depending on the clinical symptomatology) .

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

Patients of advanced age (over 65 years)

An elderly, weakened or emaciated patient is recommended a dose not exceeding half the dose prescribed for adults to patients, they are more sensitive to drugs acting on the central nervous system.

Patients with impaired liver and kidney function

With caution, prescribe the drug to patients with impaired liver function and kidney function. It is recommended that the dose be reduced. The dose is selected individually depending on the degree of hepatic and renal (creatinine clearance) deficiency.

Method of administration

- Intramuscular injections

The contents of the ampoule should be injected slowly, deep into large muscle groups.

- Intravenous injections

The contents of the ampoule should be administered slowly, at a rate of 0.5-1 ml (2.5-5 mg) per minute, in large ulnar veins.

- Intravenous drip infusion

The contents of the ampoule (10 mg / 2 ml) are diluted in at least 50 ml of a 0.9% solution of sodium chloride or a 5% solution of dextrose. Do not dilute more than 40 mg (8 ml of solution - 4 ampoules) in 500 ml of a 0.9% solution of sodium chloride or 5% solution of dextrose. A prepared solution of the Relium preparation must be administered slowly.

Too rapid intravenous administration of the drug may lead to inhibition of respiratory function and a decrease in blood pressure.

The solution must be prepared immediately before administration and used within 6 hours.

The drug Relium should not be mixed with other drugs in one syringe or infusion bottle.

For the preparation of solutions it is necessary to use glass bottles.

Sometimes during dilution of the drug, cloudiness may appear which disappears after a few minutes. If the turbidity does not disappear, do not administer the drug.

With the exception of emergency cases, with intravenous administration of the drug, there must always be another person present; a resuscitation kit should always be available. It is recommended that patients are under medical supervision for at least an additional hour after the administration of the drug. At home with the patient there must always be a responsible adult person.

Side effects:

- from the nervous system: at the beginning of treatment (especially in elderly patients) - increased fatigue, impaired concentration, lethargy, dulling of emotions, slowing of mental and motor reactions, antegrade amnesia (develops more often than when taking other benzodiazepines); drowsiness, slow reaction,headache and dizziness, confusion and disorientation, ataxia; rarely - euphoria, mood depression, numbness, dystonic extrapyramidal reactions (uncontrolled body movements, including the eyes), hyporeflexia, dysarthria; paradoxical reactions (aggressive outbreaks, psychomotor agitation, fear, suicidal tendencies, muscle spasm, confusion, hallucinations, acute arousal, irritability, anxiety, insomnia). During treatment with diazepam, there may be an earlier undiagnosed depression.

- hemopoiesis: leukopenia, neutropenia, agranulocytosis (chills, hyperthermia, sore throat, unusual fatigue or weakness), anemia, thrombocytopenia;

- from the digestive system: dry mouth or hypersalivation, heartburn, hiccough, gastralgia, vomiting, anorexia; 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: a violation of kidney function, dysmenorrhea, violations of libido;

- allergic reactions: very rarely observed anaphylactic reactions, allergic skin reactions (rash, itching, urticaria);

- 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;

- local reactions: during intramuscular injections often there is pain, and sometimes erythema at the injection site. Sometimes phlebitis may develop at the site of administration;

- other: addiction, drug dependence; rarely - oppression of the respiratory center, impaired function of external respiration, impaired vision (diplopia, blurred vision), bulimia, weight loss;

- with a sharp decrease in dose or discontinuation of reception - withdrawal syndrome (irritability, headache, anxiety, excitement, arousal, fear, nervousness, sleep disturbance, dysphoria, spasm of smooth muscles of internal organs and skeletal muscles, depersonalization, increased sweating, depression, nausea, vomiting, tremor, perception disorders, including hyperaemia, paresthesia, photophobia, tachycardia, convulsions, hallucinations, rarely - acute psychosis).

- When used in obstetrics - in term and premature infants - muscular hypotension, hypothermia, dyspnea;

- with rapid intravenous injection, blood circulation and respiratory depression were observed. The patient's horizontal position throughout the time of injection or intravenous infusion and adherence to the recommended rate of diazepam administration almost completely prevents the development of complications of this type.

If any of the side effects indicated in the instruction are aggravated, or you noticed any other side effects not listed in the instructions, report on this doctor.

Overdose:

Symptoms: drowsiness, a state of disorientation, slurred speech, a violation coordination of movements, paradoxical stimulation, decreased reflexes, visual impairment (nystagmus), tremor, bradycardia, lowering of blood pressure; in severe cases - loss of consciousness, oppression of respiratory and cardiac activity, coma. Dangerous for life can be poisoning caused by the simultaneous use of diazepam with other drugs that act depressingly on the central nervous system or diazepam with alcohol.

Treatment: symptomatic (maintaining breathing and blood pressure), forced diuresis. It is necessary to monitor the main vital functions (breathing, pulse, blood pressure). A specific antidote is flumazenil. Flumazenil It is not recommended for patients with epilepsy (may trigger the development of epileptic seizures).

Interaction:

To avoid possible drug interactions with diazepam, use other drugs only after consultation with your doctor.

The inhibitory effect of diazepam on the central nervous system is enhanced by all medicines that have a similar effect: psychotropic drugs, narcotic analgesics, preparations for general anesthesia, hypnotics, sedatives, antiepileptic, antihistamines, antipsychotics, antidepressants, opioids, sympathicolitic and anticholinergic drugs.

Drinking alcohol during treatment with diazepam increases the depressing effect on the central nervous system and can lead to the development of paradoxical reactions such as: psycho-motor agitation, aggressive behavior,respiratory depression and even coma.

When combined with muscle relaxants can enhance their effect.

Smoking weakens the action of diazepam, since it speeds up its metabolism.

Inhibitors of microsomal oxidation (including oral contraceptives, erythromycin, disulfiram, fluoxetine, isoniazid, ketoconazole, metoprolol, propranolol, propoxyphene, valproic acid, cimetidine, omeprazole) prolong the half-life and increase the effect of the drug.

Inductors of microsomal liver enzymes (rifampicin) accelerate the metabolism of diazepam and reduce its effectiveness.

The narcotic analgesics intensify euphoria, leading to an increase in psychological dependence. Also, the depressing effect on the central nervous system increases. Hypotensive drugs can increase the severity of lowering blood pressure.

With the combined use of diazepam with clozapine, an increase in respiratory depression is possible.

At simultaneous application with low-polar cardiac glycosides, it is possible to increase the concentration of the latter in the serum and the development of digitalis intoxication (as a result of competition for communication with plasma proteins).

Reduces the effectiveness of levodopa in patients with Parkinsonism.

Drugs that block tubular secretion can interfere with the conjugation of diazepam in the liver, which leads to a faster absorption or longer duration of action.

Inhibitors of monoamine oxidase, analeptics, psychostimulants change the activity of the drug.

It is possible to increase the toxicity of zidovudine.

Theophylline (used in low doses) can reduce or even change the effect preparation.

Pharmaceutically incompatible in one syringe with other drugs.

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

Special instructions:

- it is not permissible to abruptly stop treatment because of the risk of developing a "withdrawal syndrome" (headaches and muscle pains, anxiety, tension, confusion, irritability, in severe cases, derealization, depersonalization, hyperacus, photophobia, tactile hypersensitivity, paresthesia in the extremities, hallucinations and epileptic seizures).However, due to the slow half-life of diazepam, its expression is much weaker than in other benzodiazepines;

- when patients develop such unusual reactions as increased aggressiveness, acute excitations, anxiety, fear, suicidal thoughts, hallucinations, increased muscle cramps, difficult sleep, superficial sleep, treatment should be discontinued;

- When prescribing the drug for severe depression, special care must be taken since the drug can be used for suicidal intentions;

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

- repeated use of diazepam leads to a gradual weakening of its action as a result of the development of tolerance;

- the drug should be administered intravenously slowly. The rapid administration of the drug may lead to a decrease in blood pressure, impaired breathing and even cardiac arrest;

- it is recommended that great care should be taken with intravenous administration of the drug,especially in children due to an increased likelihood of side effects on the components of the drug, as well as an increased risk of developing acute respiratory failure;

- use (especially in / m or / in) at doses above 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 sucking (the so-called "sluggish child syndrome") and metabolic disorders in response to cold stress;

- children, especially at a younger age, are very sensitive to the depressing central nervous system by the action of benzodiazepines;

- the preparation contains benzyl alcohol (15.5 mg per 1 ml) in its composition, therefore, care should be taken when introducing it because of the possibility of hypersensitivity. In infants and children under 3 years of age, benzyl alcohol may cause toxic or allergic reactions;

- newborns are not recommended to prescribe drugs containing benzyl alcohol because of the possibility of developing a fatal toxic syndrome, manifested by metabolic acidosis, central nervous system depression,difficulty breathing, kidney failure, hypotension, and possibly epileptic seizures, as well as intracranial hemorrhages;

- the preparation contains ethyl alcohol (100 mg in 1 ml). It should be remembered about this using the drug in children or patients at risk, i.e. with hepatic insufficiency, epilepsy or alcoholism;

- sodium benzoate, which is part of the drug (49 mg in 1 ml), may increase the risk of jaundice in newborns;

- the constituent of propylene glycol can cause allergies;

- Benzoic acid in the preparation may cause irritation of the skin, mucous membrane and conjunctiva of the eye. It can also cause an allergy or asthma attack in patients with bronchial asthma;

- It is not recommended to use benzodiazepines and similar drugs in patients with severe hepatic insufficiency, since they can accelerate the development of hepatic encephalopathy. Liver failure can also lead to increased side effects of benzodiazepines;

- it is necessary to use the drug with caution in patients with chronic respiratory failure;

- Diazepam should be used with caution in patients with porphyria.The use of diazepam may cause an increase in the symptoms of this disease;

- Patients in advanced age (over 65 years) are recommended to reduce the dose. It is necessary to avoid prolonged use of the drug in connection with the intensification of unwanted phenomena in this age group;

- long-term use of diazepam may cause psychophysical drug dependence and the emergence of withdrawal symptoms in the event of a sudden withdrawal of diazepam. The withdrawal syndrome is characterized by psychomotor agitation, marked irritability, insomnia and mood worsening;

- Benzodiazepines and similar drugs should be used with great care in patients with alcohol and drug dependence (including drug addiction) in the anamnesis. These patients should be closely monitored when taking diazepam; are at risk of developing addiction and mental dependence;

- during long-term therapy, periodic blood tests (morphology with smear) and functional liver tests are shown.

During the period of treatment with the drug and 3 days after it is finished, you should not drink any alcoholic beverages.

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

During treatment with the preparation Relium and within 3 days after its completion it is impossible to drive vehicles and engage in other potentially hazardous activities, requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Solution for intravenous and intramuscular injection, 5 mg / ml.

Packaging:

2 ml of the drug in an ampoule of colorless glass hydrolytic class I (Hebrew Pharm.). 5 ampoules are placed in a tray of PVC.

5 ampoules (1 pallet), or 10 ampoules (2 pallets), or 50 ampoules (10 pallets) with instructions for use are placed in a cardboard box equipped with first opening control stickers.

Storage conditions:Store in a dark place at a temperature of no higher than 25 ° C.

The drug belongs to the list of psychotropic substances (list III).

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:П N015047 / 01

Date of registration:13.08.2008

The owner of the registration certificate:Tarkhominsky pharmaceutical factory "Polfa", A.O.Tarkhominsky pharmaceutical factory "Polfa", A.O. Poland

Manufacturer: & nbsp

TARCHOMIN PHARMACEUTICAL WORKS POLFA, S.A. Poland

Representation: & nbspFARMEXPERT LLCFARMEXPERT LLCRussia

Information update date: & nbsp10.09.2014

Illustrated instructions

Instructions

The Relium (Relium)