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

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.

Diazepam is a benzodiazepine derivative with a broad spectrum of action. Has anxiolytic, sedative, hypnotic, central muscle relaxant and anticonvulsant action through specific benzodiazepine receptors, most of which are in the limbic system, the hypothalamus, the cerebellum and the striatum (corpus striatum). These receptors and GABA (gamma-aminobutyric acid) form an anatomical and functional complex. When binding diazepam to the receptor, the action of gamma-aminobutyric acid increases and braking of the central nervous system occurs. The result is anticonvulsant and central miorelaksiruyuschee action. Due to the increased activity of gamma-aminobutyric acid, the activity of the neurotransmitter excitations decreases: serotonin, norepinephrine and acetylcholine and, consequently, the anxiolytic, hypnotic and sedative effect of the drug is provided.

Pharmacokinetics:

With the / m introduction, the absorption can be slow and unstable (depends on the place of administration); when introduced into the deltoid muscle - adsorption is fast and complete. The maximum therapeutic concentration is achieved with a / m injection after 0.5-1.5 hours and with / in the introduction within 0.25 hours. Equilibrium concentration is achieved with constant intake after 1-2 weeks. Diazepam and its metabolites penetrate the blood-brain barrier 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%. Metabolized in the liver 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 mildew. The excretion has a two-phase character: behind the initial phase of rapid and extensive distribution (period half-life (T_1/2) - 3 hours) follows a prolonged phase (T_1/2-20-70 h). T_1/2desmethyldiazepam - 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) 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 a long half-life, elimination after cessation of treatment is slow, because metabolites persist in the blood for several days or even weeks.

Indications:

- Anxiety disorders.

- Spasm of skeletal muscles with local trauma; spastic conditions associated with the defeat of the brain or spinal cord (cerebral palsy, athetosis, tetanus); myositis, bursitis, arthritis, rheumatic pelviscandiloarthritis, progressive chronic polyarthritis; Arthrosis, accompanied by the tension of skeletal muscles; vertebral syndrome, angina, tension headache.

- An abstinent alcoholic syndrome: anxiety, tension, agitation, tremor, transient reactive conditions.

- As part of complex therapy: hypertension, psychosomatic disorders in obstetrics and gynecology: menopausal and menstrual disorders, relief of labor, premature detachment of the placenta, gestosis (preeclampsia and eclampsia); status epilepticus, tetanus.

- Premedication before surgical interventions and endoscopic manipulation, general anesthesia, as a component of combined general anesthesia.

Contraindications:

Hypersensitivity to diazepam and derivatives of benzodiazepine and other components of the drug; coma, shock, myasthenia gravis; suicidal tendencies; alcohol dependence, acute alcohol intoxication, with the weakening of vital functions (in history, except acute withdrawal), acute intoxication with drugs depressing the central nervous system (including narcotic analgesics, sleeping pills, psychotropic drugs), drug dependence; hypercapnia; lactation period, acute attack of glaucoma, closed angle glaucoma, cerebral and spinal ataxia, hepatitis, nocturnal apnea, pregnancy (I trimester), severe chronic obstructive pulmonary disease (risk of progression of respiratory failure), acute respiratory failure, children up to 30 days inclusive.

Carefully:Chronic lung diseases due to a possible increase in respiratory failure, severe renal and hepatic insufficiency, severe heart failure,epilepsy or epileptic seizures in the anamnesis (initiation of diazepam treatment or its abrupt reversal may accelerate the development of seizures or epileptic status), absence of symptoms or Lennox-Gastaut syndrome (with iv introduction contributes to the development of tonic epileptic status), hyperkinesis, drug dependence in history, addiction to abuse of psychoactive drugs, organic brain diseases, hypoproteinemia, old age.

Pregnancy and lactation:

Apaurin is not recommended during pregnancy. It can be prescribed only for vital indications, when the expected favorable effect justifies the risk to the fetus. Apaurin is excreted in breast milk, therefore it is not recommended during lactation, except for vital indications, in this case, breast-feeding should be interrupted.

Dosing and Administration:

Intramuscular or intravenous administration. The dose of the drug is selected individually, depending on the severity of the symptoms, age and condition of the patient.

In acute conditions, the drug can be administered every hour, in other cases, the interval between admission is usually 4 hours.Elderly and weakened patients, it is recommended that minimal doses (2 to 5 mg) be prescribed, if necessary with their subsequent gradual increase, and also when combined with other sedatives.

Mode of application:

Intramuscular administration:

The drug should be injected deep into the muscle.

Intravenous administration:

The drug should be administered strictly intravenously (into a large vein), very slowly, at a rate not higher than 5 mg (1 ml) per minute.

Drip intravenous infusion:

Solution for infusion (5 or 10% glucose or 0.9% solution NaCl) must be prepared immediately before use. The contents of the ampoule (no more than 2 ampoules at a time) are added to the infusion solution (at least 250 ml) which must be thoroughly mixed and immediately used.

The solution of Apaurin should not be mixed with solutions of other drugs in a syringe or other injection tanks. Pharmaceutically incompatible in one syringe with other drugs.

Alarm states: from 5 to 10 mg intravenously or intramuscularly. If necessary, the administration can be repeated after 4 hours.

Alcohol withdrawal syndrome: from 10 to 20 mg intravenously or intramuscularly. If necessary, the dose can be repeated every 4 hours.

Epileptic status:

Adults: from 0,15 to 0,25 mg / kg of body weight of the patient intravenously slowly or intramuscularly. If necessary, repeat the dose every _1/2 - 1 hour or intravenously administered drip administration (maximum dose of 3 mg / kg body weight per day).

Children from 30 days to 5 years: from 0.2 to 0.5 mg intravenously slowly every 2-5 minutes, but not more than 5 mg.

Children from 5 years and older: 1 mg every 2-5 minutes intravenously slowly, to a maximum dose of 10 mg. If necessary, repeat the dose after 4-6 hours.

Tetanus:

Adults: from 0.1 to 0.3 mg / kg body weight intravenously slowly with 1 - 4 hour intervals, or from 3 to 4 mg / kg body weight per day intravenously drip.

Children from 6 months to 5 years: from 1 to 2 mg intravenously or intramuscularly, if necessary, repeat the dose every 4 hours.

Children from 5 years and older: from 5 to 10 mg intravenously or intramuscularly, if necessary, repeat the dose every 4 hours.

Muscle spasms: from 10 to 20 mg intravenously or intramuscularly, 1 or 2 times a day (children from 2 to 10 mg).

Psychosomatic disorders in obstetrics and gynecology:

Preeclampsia: Initially, prescribe 10 to 20 mg intravenously slowly, then switch to taking the drug inside 5 to 10 mg 3 times a day.

Eclampsia: Initially, prescribe 10 mg intravenously slowly, then intravenously drip (up to 100 mg per day).

Premature detachment of the placenta: from 10 to 20 mg intravenously slowly or intramuscularly. If necessary, the dose can be repeated.

Childbirth: from 10 to 20 mg iv or in / m with the opening of the cervix for 2 - 3 fingers.

Premedication before surgical interventions and endoscopic manipulation, general anesthesia, as a component of combined general anesthesia: from 10 to 20 mg (children from 2 to 10 mg) 1 hour before the proposed intervention.

Introductory anesthesia: from 0.2 to 0.5 mg / kg body weight intravenously slowly.

Cardioversion, endoscopy, radiological studies and small surgical procedures: from 10 to 30 mg intravenously slowly (children from 0.1 to 0.2 mg / kg body weight). A sharp discontinuation of the drug may cause withdrawal symptoms, so the drug should be withdrawn gradually.

Side effects:

From the nervous system: increased fatigue, disorientation, slowing of mental and motor reactions, anterograde amnesia, lethargy, drowsiness, muscle weakness; dulling of emotions, loss of attention,ataxia; confusion, rarely - euphoria, catalepsy, dystonic extrapyramidal reactions (uncontrolled body movements, including the eyes), hyporeflexia; acute agitation, anxiety, sleep disturbance - paradoxical reactions, headache, dizziness, tremor, memory impairment, vertigo, gait instability and poor coordination of movements, dysarthria.

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

From the digestive system: heartburn, hiccough, gastralgia, vomiting, decreased appetite; impaired liver function, increased activity of "liver" transaminases and alkaline phosphatase (APF), jaundice, constipation, dry mouth or hypersalivation, nausea.

From the CAS side: fainting, bradycardia, palpitations, tachycardia, cardiovascular collapse, lowering of blood pressure (BP), conduction disturbance.

From the genitourinary system: urinary incontinence, urinary retention, impaired renal function, increased or decreased libido, dysmenorrhea, menstrual irregularities.

From the sense organs: blurred vision, diplopia, nystagmus.

Influence on the fetus: teratogenicity (especially I trimester), central nervous system (CNS) depression, respiratory failure and suppression of sucking reflex in newborns whose mothers used the drug.

Allergic reactions: urticaria, rash, itchy skin.

Local reactions: phlebitis or venous thrombosis (redness, swelling, or pain at the injection site).

Other: addiction, drug dependence, rarely - respiratory center depression, disturbance of external respiration function, apnea, bulimia, weight loss, muscle weakness, general weakness.

With a sharp reduction in dose or discontinuation - withdrawal syndrome (irritability, headache, anxiety, agitation, agitation, a sense of fear, nervousness, sleep disturbances, dysphoria, spasm of smooth muscles of internal organs and skeletal muscles, depersonalization, increased sweating, depression, nausea, vomiting, tremor, perceptual disorders, h. hyperakkuziya, parestezii, photophobia, tachycardia, convulsions, hallucinations, rarely - acute psychosis). When applying IV or IM in obstetrics - in term and premature babies - muscle hypotension, hypothermia, dyspnea.

Overdose:

Symptoms: drowsiness, confusion, paradoxical agitation, deafness, decreased reaction to painful irritations, areflexia, deep sleep, dysarthria, ataxia, visual disturbances (nystagmus), tremor, bradycardia, shortness of breath or shortness of breath, apnea, severe weakness, decreased blood pressure, collapse, oppression of cardiac and respiratory activity, apnea, coma.

Treatment: artificial lung ventilation, gastric lavage, forced diuresis. Symptomatic therapy. A specific antidote, a benzodiazepine antagonist - flumazenil, intravenously. However, its action is much shorter than the action of diazepam, so the patient should be observed for several hours after awakening. The use of flumazenil is not indicated in patients with epilepsy who have been treated with benzodiazepines, since its antagonistic effect may provoke the development of epileptic seizures. Control of the functions of breathing and cardiovascular system. Hemodialysis is ineffective.

Interaction:

Simultaneous administration of Apaurin and inhibitors of microsomal oxidation (incl.cimetidine, oral contraceptives, erythromycin, disulfiram, fluoxetine, isoniazid, itraconazole, fluconazole, ketoconazole, metoprolol, propranolol, valproic acid) prolongs the half-life of diazepam and enhances its effect. Inducers of microsomal liver enzymes reduce the effectiveness of diazepam. Increases the inhibitory effect on the CNS ethanol. Antacid drugs reduce the rate of absorption of diazepam from the gastrointestinal tract (GI tract), but not its completeness.

Diazepam reduces the effect of levodopa in patients with Parkinsonism.

Hypotensive drugs increase the severity of blood pressure lowering with a simultaneous appointment with diazepam.

Against the background of simultaneous administration of clozapine, an increase in respiratory depression is possible.

With simultaneous use 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 for the connection with plasma proteins).

Omeprazole prolongs diazepam clearance time.

Inhibitors of monoamine oxidase (MAO), analeptics, psychostimulants - reduce activity.

Diazepam may increase the toxicity of zidovudine.

Rifampicin can increase the excretion of diazepam and lower its concentration in the plasma. Theophylline (used in low doses) can reduce or even pervert the sedative effect.

Pharmaceutically incompatible in one syringe with other medicines.

Special instructions:

With the development of paradoxical reactions (acute agitation, anxiety, sleep disturbances, hallucinations), the drug should be discarded. Apaurin can affect the psychomotor abilities of the patient, especially if taken concomitantly with alcohol or drugs depressing the central nervous system. In the process of treatment, patients are strictly prohibited from drinking ethanol. The risk of forming drug dependence increases with the use of large doses, the duration of treatment, in patients who previously abused alcohol and drugs. In the case of a relationship, abrupt abolition of Apaurin is accompanied by withdrawal syndrome (headaches and muscle pains, anxiety, confusion, irritability, in severe cases - hyperacusia, paresthesia in the extremities, light and tactile hypersensitivity, hallucinations and epileptic seizures).

Strict monitoring of patients with severe kidney and liver diseases, heart failure, mental disorders, as well as patients with drug, alcohol and drug dependence is necessary.

Children, especially at a young age, are very sensitive to the CNS depressing action of benzodiazepines. 1 ampoule (2 ml) contains 31.4 mg of benzyl alcohol, which can cause a toxic reaction in newborns, manifested by metabolic acidosis, CNS depression, difficulty breathing, kidney failure, lower blood pressure and possibly epileptic seizures, as well as intracranial hemorrhages.

As with intramuscular administration of other drugs, intramuscular administration of diazepam (but not oral or intravenous) may lead to an increase in serum creatinine phosphokinase, the amount of which reaches a peak 12-24 hours after administration. This must be remembered for a differential diagnosis with myocardial infarction.

Diazepam should be avoided in the arterial bed due to the risk of necrotic complications. Intravenous administration may be accompanied by prolonged sedation or development and anterogradeTherefore, outpatients who are prescribed parenteral (especially intravenous) administration of Apaurin should be monitored for at least 1 hour and leave the facility with the accompanying person in charge.

Use (especially in / m or / in) at doses above 30 mg and for 15 hours before delivery or during labor 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 (syndrome of "flaccid child") and metabolic disorders in response to cold stress.

Effect on the ability to drive transp. cf. and fur:During drug treatment, it is recommended to refrain from managing motor vehicles, special equipment or engage in potentially dangerous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:Solution for intravenous and intramuscular injection, 5 mg / ml.

Packaging:

2 ml of the preparation in a glass ampoule of amber color (glass type I). The ampoule contains a colored dot indicating the line of the broken ampoule, and a color coding ring.

5 ampoules per blister.2 blisters in a cardboard pack together with instructions for use.

Storage conditions:

The drug belongs to the list of 1 potent substances of the Standing Committee on Drug Control M3 RF.

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

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N014583 / 01

Date of registration:02.06.2008

Expiration Date:Unlimited

Date of cancellation:2018-04-28

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp28.04.2018

Illustrated instructions

Instructions

Apaurin (Apaurin)