Relaniuma: instructions for using the medicine, structure, Contraindications

Active material: Diazepam
When ATH: N05BA01
CCF: Tranquillizer (anxiolytic)
ICD-10 codes (testimony): A35, F10.3, F10.4, F40, F41.2, F48.0, G40, G41, I10, I61, I63, N94.3, N95.1, N95.3, O15, R25.2, Z51.4
When CSF: 02.04.01
Manufacturer: WARSAW PHARMACEUTICAL WORK POLFA S.A. (Poland)

Relaniuma: dosage form, composition and packaging

Solution for in / and the / m clear, colorless or yellow-green.

Excipients: propylene glycol, ethanol 96%, benzyl alcohol, Sodium benzoate, acetic acid glacial, acetic acid 10% (to pH 6.3-6.4), water d / and.

2 ml – ampoule (5) – packs cardboard.
2 ml – ampoule (10) – packs cardboard.
2 ml – ampoule (50) – packs cardboard.

Relaniuma: pharmachologic effect

Anksioliticheskiй preparation (tranquillizer), benzodiazepine derivative.

Diazepam has a depressing effect on the CNS, realized mainly in the thalamus, hypothalamus and the limbic system. It enhances the inhibitory action of gamma-aminobutyric acid (GABA), which is one of the major mediators pre- and postsynaptic inhibition of neurotransmission in the CNS. It possesses anxiolytic, sedativnыm, hypnotic, muscle relaxant and anticonvulsant action.

The mechanism of action of diazepam is determined by the stimulation of benzodiazepine receptors supramolecular GABA-benzodiazepine-receptor complex hlorionofor, which leads to the activation of the GABA receptor, causing a decrease in excitability of the subcortical brain structures, tormozhenie polisinapticheskih spinalьnыh reflexes.

Relaniuma: pharmacokinetics

Absorption

After the / m of diazepam is absorbed slowly and unevenly, depending on the site of administration; when administered in the deltoid muscle absorption rapid and complete. Bioavailability is 90%. C_max when i / m administration is achieved through 0.5-1.5 no, at / in the introduction for 0.25 no.

Distribution

With constant use of C_ss achieved through 1-2 Sun.

Binding to plasma proteins is 98%.

Diazepam and its metabolites cross the BBB and placental barrier, excreted in breast milk in concentrations, relevant 1/10 plasma concentration.

Repeated use of the drug is observed pronounced accumulation of diazepam and its active metabolites.

Metabolism

It is metabolized in the liver with the participation of isoenzymes CYP2C19, CYP3A4, CYP3A5 and CYP3A7 on 98-99% to form a very active metabolite desmetildiazepama and less active – temazepam and oxazepam.

Deduction

T_1/2 desmetildiazepama is 30-100 no, Temazepam – 9.5-12.4 h and oxazepam – 5-15 no.

Report the news – 70% (in the form of glucuronides), in unchanged form – 1-2%, less 10% – with feces.

It refers to benzodiazepines with a long T_1/2. After the cessation of treatment metabolites retained in blood for several days or even weeks.

Pharmacokinetics in special clinical situations

T_1/2 may increase in neonates – to 30 no, in elderly patients – to 100 no, in patients with hepatic and renal failure – to 4 d.

Relaniuma: testimony

• treatment of neurotic and neurosis-like disorders with manifestation of anxiety;
• relief of psychomotor agitation, associated with anxiety;
• relief of epileptic seizures and convulsive conditions of various etiologies;
• states, accompanied by increased muscle tone (incl. stolbnyak, acute stroke);
• relief of withdrawal symptoms and delirium in alcoholism;
• for premedication and ataralgesia in combination with analgesics and other neurotropic drugs in various diagnostic procedures, surgical and obstetric practice;
• in the clinic of internal diseases: in the treatment of hypertension (accompanied by anxiety, hyperexcitability), hypertensive crisis, vasospasm, menopausal and menstrual disorders.

Relaniuma: dosing regimen

With the aim of relief of psychomotor agitation, associated with anxiety, appoint 5-10 mg / slow, if necessary through 3-4 h drug is administered again in the same dose.

At stolbnyake appoint 10 mg / slow or deep / m, then / drip administered 100 mg diazepam 500 ml 0.9% sodium chloride solution or 5% solution of glucose at a speed 5-15 mg / h.

At status epilepticus appoint / m or / by 10-20 mg, if necessary through 3-4 h drug is administered again in the same dose.

To spasmolysis skeletal muscle – by 10 mg / m for 1-2 hours before the operation.

IN obstetrics appoint / m 10-20 mg for cervical dilatation on 2-3 finger.

Infants after the 5th week of life (senior 30 days) administered in / slow 100-300 ug / kg of body weight up to a maximum dose of 5 mg, if necessary, through the introduction of a repeat 2-4 no (depending on the clinical symptoms).

For children 5 and older the drug is introduced into / in slowly 1 mg every 2-5 min to a maximum dose 10 mg; if necessary, the administration can be repeated after 2-4 no.

Relaniuma: side effects

From the central and peripheral nervous system: at the beginning of treatment (especially in elderly patients) – drowsiness, dizziness, fatigue, impaired concentration, ataxia, disorientation, blunting of emotions, mental retardation and motor responses, anterogradnaya amnesia (It develops more often, than when other benzodiazepines); rarely – headache, euphoria, depression, tremor, catalepsy, confusion, dystonic extrapyramidal reactions (uncontrolled movements), asthenia, muscular weakness, giporefleksiя, dysarthria; in some cases – paradoxical reactions (outbreaks of aggression, psychomotor agitation, fear, suicidal, muscle spasm, confusion, hallucinations, alarm, sleep disorders).

From the hematopoietic system: leukopenia, neutropenia, agranulocytosis (chills, hyperthermia, sore throat, severe tiredness or weakness), anemia, thrombocytopenia.

From the digestive system: dry mouth or hypersalivation, heartburn, Ikotech, gastralgia, nausea, vomiting, decreased appetite, constipation, abnormal liver function, increase in liver transaminases and alkaline phosphatase, jaundice.

Cardio-vascular system: hypotension, tachycardia.

From the urinary system: incontinence or urinary retention, impairment of renal function.

On the part of the reproductive system: increased or decreased libido, dysmenorrhoea.

The respiratory system: respiratory depression (at too rapid introduction of the drug).

Allergic reactions: skin rash, itch.

Local reactions: flebyt thrombosis or venoznыy (Krasnoja, swelling, pain) at the injection site.

Other: adaptation, drug dependence; rarely – depression of the respiratory center, blurred vision (diplopia), Bulimia, weight loss.

With a sharp decrease in dose or discontinuation of – withdrawal (irritability, headache, alarm, fear, psychomotor agitation, sleep disorders, disforija, spasm of smooth muscles of internal organs and skeletal muscles, depersonalization, increased sweating, depression, nausea, vomiting, tremor, perception disorders, incl. hyperacusis, paresthesia, photophobia, tachycardia, convulsions, hallucinations; rarely – psychotic disorders). When used in obstetrics neonates – hypomyotonia, gipotermiя, dyspnoea.

Relaniuma: Contraindications

• severe form of myasthenia gravis;
• coma;
• shock;
• zakrыtougolynaya glaucoma;
• indications in the anamnesis of the phenomena of dependence on narcotic drugs, alcohol (except for the treatment of alcohol withdrawal syndrome and delirium);
• sleep apnea syndrome;
• state of alcoholic intoxication of varying severity;
• acute drug intoxication, have a depressing effect on the CNS (narcotic, hypnotics and psychotropic drugs);
• severe chronic obstructive pulmonary disease (the risk of progression of respiratory failure);
• acute respiratory failure;
• Children up to age 30 days inclusive;
• pregnancy (especially I and III trimesters);
• lactation (breast-feeding);
• hypersensitivity to benzodiazepines.

FROM caution appoint absences (little evil) or Lennox-Gastaut syndrome (at / in the introduction can trigger the development of tonic status epilepticus), epilepsy or a history of epileptic seizures (initiation of treatment with diazepam or abrupt withdrawal may accelerate the development of seizures or status epilepticus), hepatic and / or renal failure, cerebralьnoй and spinalьnoй ataxias, when hyperkinesis, propensity to abuse of psychotropic drugs, depression, organic brain diseases (possible paradoxical reactions), when hypoproteinemia, elderly patients.

Relaniuma: Pregnancy and lactation

The drug is contraindicated during pregnancy and lactation.

Relaniuma^® It has a toxic effect on the fetus and increase the risk of birth defects when used in the I trimester of pregnancy. Taking the drug at therapeutic doses in later stages of pregnancy can cause depression of the central nervous system of the fetus. The constant use during pregnancy can cause physical dependence – possible withdrawal symptoms in the newborn.

When using RELANIUM^® in doses more 30 mg for 15 hours before birth or during labor may cause newborn respiratory depression (until apnea), decreased muscle tone, decrease in blood pressure, gipotermiю, weak act of sucking (“flaccid syndrome child”).

Relaniuma: Special instructions

With extreme caution should be used when severe depression diazepam, tk. the drug can be used for the implementation of suicidal intentions.

IV solution of RELANIUM^® should be administered slowly, into a large vein, at least, during 1 per min 5 mg (1 ml) product. Not recommended for continuous I / Infusion – possible precipitation and adsorption of the drug material from PVC infusion cylinders and tubes.

When renal or hepatic failure and prolonged use is necessary to control the picture of peripheral blood and liver enzymes.

The risk of developing drug dependence increases with the use of RELANIUM^® high dose, with a significant duration of treatment for patients, previously abused alcohol or drugs. Unnecessarily drug should not be used for a long time. It is unacceptable abrupt discontinuation of treatment because of the risk of withdrawal, However, due to the slow elimination of diazepam, manifestation of this syndrome is expressed much weaker, than the other benzodiazepines.

If you have any patients with such unusual reactions, as increased aggressiveness, psychomotor agitation, alarm, a sense of fear, suicidal thoughts, hallucinations, gain muscle cramps, difficult falling asleep, shallow sleep treatment should be discontinued.

Start of treatment with RELANIUM^® or abrupt withdrawal in patients with epilepsy or a history of seizures may accelerate the development of seizures or status epilepticus.

RELANIUM should be used with extreme caution and not exceeding the recommended doses.^® in elderly patients.

If necessary, use of the drug in patients with liver and kidney should assess the risks and benefits of therapy.

Relaniuma^® not administered intra-because of the risk of gangrene.

With prolonged use of the drug may develop addiction.

During treatment, alcohol is prohibited.

Use in Pediatrics

Children, especially for younger children, very sensitive to the inhibitory effect of benzodiazepines on the central nervous system.

Newborns are not recommended to prescribe drugs, containing benzyl alcohol, tk. may develop a toxic syndrome, proyavlyayushtegosya metabolic atsidozom, CNS depression, difficulty breathing, renal failure, hypotension and, perhaps, seizures, as well as intracranial hemorrhage.

Effects on ability to drive vehicles and management mechanisms

Patients, receiving the drug, It should refrain from activities potentially hazardous activities, require increased attention and psychomotor speed reactions.

Relaniuma: overdose

Symptoms: drowsiness, depression of consciousness of varying severity, paradoxical excitement, reduced reflexes to arefleksiya, decreased response to pain stimuli, dysarthria, ataxia, visual impairment (nistagmo), tremor, bradycardia, decrease in blood pressure, collapse, oppression heart, respiratory depression, coma.

Treatment: gastric lavage, diurez, administration of activated charcoal; symptomatic therapy (maintenance of respiration and blood pressure), ventilation.

A specific antidote is flumazenil, which should be applied in the hospital. Flumazenil is not indicated in patients with epilepsy, who were treated with benzodiazepines. In such cases, antagonistic action with respect to benzodiazepines can provoke the development of epileptic seizures.

Relaniuma: drug interaction

MAO inhibitors, strychnine and corazole antagonize the effects of RELANIUM^®.

With the simultaneous use of RELANIUM^® with drugs, sedativnыmi sredstvami, opioid analgesics, other tranquilizers, benzodiazepines, miorelaksantami, General anesthetics, antidepressants, neuroleptics, as well as with ethanol has been a sharp increase in inhibitory action on the central nervous system.

In an application with cimetidine, disulьfiramom, Erythromycin, fluoxetine, as well as with oral contraceptives and medications estrogensoderjath, that competitively inhibit the metabolism in the liver (oxidation) – may slow the metabolism of diazepam and increase its concentration in blood plasma.

Isoniazid, ketoconazole, and metoprolol also slow down the metabolism of diazepam and increase its concentration in blood plasma.

Propranolol and valproic acid increase the concentration of diazepam in blood plasma.

Rifampicin can induce metabolism of diazepam, which leads to a decrease of its concentration in plasma.

Inducers of microsomal liver enzymes reduce the effectiveness of RELANIUM^®.

Opioid analgesics increase the inhibitory effect of RELANIUM^® CNS.

At simultaneous application with antihypertensive agents may increase the hypotensive effect.

While the use of clozapine may be increased respiratory depression.

With the simultaneous use of RELANIUM^® with cardiac glycosides may increase the concentration of the latter in blood serum and the development of digitalis intoxication (due to the concurrent communication with plasma proteins).

Relaniuma^® reduces the effectiveness of levodopa in patients with Parkinson's.

Omeprazole prolongs the elimination of diazepam.

Respiratory analeptics, psychostimulants reduce the activity of RELANIUM^®.

When used simultaneously with RELANIUM^® may increase the toxicity of zidovudine.

Theophylline (low dose) may reduce the sedative effect of RELANIUM^®.

Premedication by RELANIUM^® to reduce the dose of fentanyl, required for the introduction of general anesthesia, and reduces the onset of general anesthesia.

Pharmaceutical interaction

Relaniuma^® incompatible in the same syringe with other drugs.

Relaniuma: terms of dispensing from pharmacies

The drug is released under the prescription.

Relaniuma: terms and conditions of storage

Relaniuma^® refers to the list №1 potent substances Standing Committee on Drug Control MoH.

The drug should be stored out of reach of children, dark place at a temperature of 15 ° to 25 ° C. Shelf life – 5 years.