Midazolam Hamelin (Midazolam-hameln)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceMidazolamMidazolam
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    • Dosage form: & nbspsolution for intravenous and intramuscular administration
    Composition:

    1 ml of solution for injection contains:

    Active substance: midazolam hydrochloride monohydrate 5.00 mg (in terms of midazolam).

    Excipients: sodium chloride 8.04 mg, hydrochloric acid solution 1M q.s., water for injection up to 1 ml.

    Description:A clear, colorless solution.
    Pharmacotherapeutic group:Sleeping Pills
    ATX: & nbsp

    N.05.C.D.08   Midazolam

    Pharmacodynamics:

    Midazolam is a hypnotic from a group of benzodiazepine derivatives. Has a sedative and hypnotic effect of pronounced intensity, as well as anxiolytic, anticonvulsant and central muscle relaxant action. Pharmacological action is characterized by short duration because of rapid degradation of midazolam. Quickly causes the onset of sleep (after 20 minutes), has little effect on the structure of sleep, almost does not have the effect of aftereffect.

    The onset of action: sedative - 15 min (IM),1,5-5 minutes (iv administration); introductory general anesthesia with intravenous administration - 0,75-1,5 min (with premedication of narcotic drugs), 1,5-3 min (without premedication with narcotic drugs). The duration of the amnestic effect is in direct proportion to the dose. Time to exit from the general anesthesia - an average of 2 hours. After an / m or IV application, anterograde amnesia of short duration occurs.

    Pharmacokinetics:

    Absorption

    With intramuscular administration, the absorption of midazolam from muscle tissue passes quickly and completely. The maximum concentration in plasma is reached within 30 minutes. Absolute bioavailability after intravenous injection is more than 90%.

    Distribution

    When administered intravenously, the distribution is biphasic. The equilibrium volume of distribution is 0.7-1.2 l / kg. The connection with plasma proteins is 96-98%. It binds mainly to albumin Midazolam penetrates through gistogematicheskie barriers, incl. hematoencephalic and placental barriers, as well as in breast milk. Small concentrations are found in the cerebrospinal fluid.

    Biotransformation

    Midazolam is almost completely excreted by biotransformation. The fraction of the dose excreted by the liver is 30-60%. Hydroxylated with the isoenzyme CYP3A4 to α-hydroxymidazolam (the main metabolite in plasma and urine). Plasma concentration of α-hydroxymidazolam reaches 12% of the starting material. Pharmacological activity is 10% of the activity of midazolam.

    Excretion

    In healthy volunteers, the elimination half-life (T1/2 ) of midazolam is 1.5-2.5 hours. The plasma clearance is 300-500 ml / min. It is excreted mainly by the kidneys (60-80% of the administered dose) mainly in the form of α-hydroximidazolamglucuronide. Less than 1% is excreted unchanged in the urine. T1/2 α-hydroxymidazolam is <1 h.

    Pharmacokinetics in specific patient groups

    Elderly patients. In persons over 60 years of age, T1/2 can be increased fourfold.

    Children. After intravenous administration to children 3-10 years of age, T1/2 in comparison with adults shorter (1-1.5 h), which is explained by the more intensive metabolism of midazolam.

    Newborns. In newborns, T1/2 an average of 6-12 hours.

    Patients with excessive body weight. In obese individuals, T1/2 is about 5.9 hours (in people with a normal body weight - 2.3 hours), which corresponds to a 50% increase (adjusted for the total volume of distribution). Differences in the rate of excretion are absent.

    Patients with hepatic insufficiency. In patients with liver cirrhosis T1/2 and excretion may extend.

    Patients with renal insufficiency. In patients with chronic renal failure T1/2 the same as in healthy volunteers.

    Severely ill patients. In seriously ill patients, T1/2 Midazolam is extended to six times.

    Patients with heart failure. In patients with chronic heart failure compared to healthy volunteers, T1/2 lengthens.

    Indications:

    Adults:

    sedation with preservation of consciousness before diagnostic or medical procedures, performed under local anesthesia or without it, and also during their conduct; premedication before introductory anesthesia; introductory anesthesia; in the quality of the sedative with combined anesthesia; long sedation in intensive care.

    Children:

    sedation with preservation of consciousness before diagnostic or medical procedures, performed under local anesthesia or without it, and also during their conduct; premedication before introductory anesthesia; long sedation in intensive care.

    Contraindications:

    Hypersensitivity to benzodiazepine derivatives or to any component of the drug.

    Sedation in patients with severe respiratory failure or with acute respiratory distress syndrome.

    Carefully:Chronic heart failure, respiratory insufficiency, liver failure, chronic renal failure, obesity, childhood (especially newborns and prematurity), organic brain damage, alcohol and drug intoxication with the suppression of vital functions, acute emergency (coma, shock).
    Pregnancy and lactation:

    Data for assessing the safety of the drug during pregnancy is not enough. Benzo diazepine derivatives should be used during pregnancy only if absolutely necessary. When using midazolam in the third trimester of pregnancy or during labor, it can lead to a violation of the heart rhythm in the fetus, muscle hypotension, impaired sucking, hypothermia and respiratory depression in the newborn. In addition, the use of the drug in later pregnancy can cause physical dependence in the newborn with the risk of developing the syndrome of "withdrawal".

    Midazolam penetrates into breast milk, so its use during breastfeeding is not recommended, the resumption of breastfeeding is allowed 24 hours after the last dose of midazolam.

    Dosing and Administration:

    Intravenous, intramuscular.

    The dose is selected individually, to achieve the desired severity of sedation, appropriate clinical needs, the physical condition and age of the patient, as well as concomitant drug therapy.

    For intravenous infusion, a solution is prepared in a ratio of 15 mg of midazolam to 100-1000 ml of one of the following solutions for injection: 0.9% sodium chloride solution, 5 or 10% dextrose solution, Ringer's solution.

    The standard dosage regimen is shown in the table:

    Indication

    Adults < 60 years

    Adults ≥ 60 years /

    depleted or chronically ill

    Children

    Sedative effect in a conscious state

    I / O slowly

    Initial dose: 2-2.5 mg

    Subsequent dose: 1 mg

    Total dose: 3.5-7.5 mg

    I / O slowly

    Initial dose: 0.5-1 mg

    Subsequent doses: 0.5-1 mg

    Total dose: <3.5 mg

    in / in patients 6 months - 5 years

    Initial dose: 0.05-0.1 mg / kg

    Total dose: <6 mg

    IV in patients 6-12 years old

    Initial dose: 0.025-0.05 mg / kg

    Total dose: <10 mg

    in / m 1-15 years

    0.05-0.15 mg / kg

    For premedication

    I / O slowly

    0.07-0.1 mg / kg

    I / O slowly

    0.025-0.05 mg / kg

    in / m 1-15 years

    0,08-0,2 mg / kg

    Introductory anesthesia

    I / O slowly

    0,15-0,2 mg / kg (0,3-0,35 mg / kg without premedication)

    I / O slowly

    0.1-0.2 mg / kg (0.15-0.3 mg / kg without premedication)


    Sedative component in combined anesthesia

    I / O slowly

    single doses of 0.03-0.1 mg / kg or continuous infusions of 0.03-0.1 mg / kg / h

    I / O slowly

    doses lower than those recommended for adults <60 years


    Sedation in intensive care

    I / O slowly

    Shock dose: 0.03-0.3 mg / kg with an increase of 1-2.5 mg

    Maintenance dose: 0.03-0.2 mg / kg / h

    in / in neonates <32 weeks of gestational age

    0.03 mg / kg / h

    in / in newborns> 32 weeks and children under 6 months

    0.06 mg / kg / h

    IV in patients> 6 months of age

    Shock dose: 0.05-0.2 mg / kg

    Maintenance dose: 0.06-0.12 mg / kg / h

    Sedation with preservation of consciousness before diagnostic or treatment procedures, performed under local anesthesia or without it, and also during their

    Adults

    The drug solution is administered intravenously slowly, at a rate of about 1 mg per 30 seconds. In adults younger than 60 years, the initial dose is 2-2.5 mg, the introduction is carried out 5-10 minutes before the procedure. Further doses of 1 mg can be administered as needed.The average total doses are in the range 3.5-7.5 mg. A total dose of more than 5 mg is usually not required. In adults over 60 years old, depleted or chronically ill patients, the application begins with a dose of 0.5-1 mg. Further doses of 0.5-1 mg can be administered as needed. A total dose greater than 3.5 mg is usually not required.

    Children

    Intravenous application: the initial dose of midazolam is administered for more than 2-3 minutes. Then wait 2-5 minutes to fully assess the sedation before starting the procedure or repeat the dose.

    Children from 6 months to 5 years: the initial dose of 0.05-0.1 mg / kg, to achieve the expected result, a total dose of up to 0.6 mg / kg is sometimes required, but the total dose should not exceed 6 mg.

    Children from 6 to 12 years: the initial dose of 0.025-0.05 mg / kg. The total dose to 0.4 mg / kg, the maximum -10 mg.

    Children from 12 to 16 years: the dosing regimen as in adults.

    Intramuscular application: the dose range is 0.05-0.15 mg / kg. The total dose is no more than 10 mg.

    Premedication before introductory anesthesia

    Adults

    The drug is administered intramuscularly for 20-60 minutes before the introduction of anesthesia: adults under 60 years - 0.07-0.1 mg / kg, patients older than 60 years, depleted, or chronically ill dose are individually selected (usually it is 0.025-0.05 mg / kg).The usual dose is 2-3 mg.

    Children over 6 months

    Intramuscularly (in exceptional cases, since the injection is painful) at a dose of 0.08-0.2 mg / kg.

    In children younger than 6 months, including newborns, the drug is not used for this indication.

    Introductory anesthesia

    The drug is administered intravenously, slowly, fractionally, every repeated dose (an increase of no more than 5 mg) is administered within 20-30 seconds, with an interval of 2 minutes. To complete the input to anesthesia, the initial dose is increased by approximately 25% or inhalation anesthetics are used. When used in combination with other preparations for introductory anesthesia, the initial dose of each drug should be significantly reduced. The desired level of anesthesia is achieved through a step-by-step introduction.

    Adults under the age of 60 years - 0,15-0,2 mg / kg (in non-premedicated adults under 60 years, the dose may be increased - 0,3-0,35 mg / kg). In non-treatable cases, the dose is increased to 0.6 mg / kg, but such large doses can increase the process of consciousness recovery. Adults over the age of 60 years, depleted or chronically ill patients - 0.1-0.2 mg / kg (not undergoing premedication to patients over 60 years of age usually require an increased dose of -0.15-0.3 mg / kg,not subjected to premedication to patients with serious systemic diseases or other problems, usually requires a smaller amount - 0,15-0,25 mg / kg).

    Sedative component with combined anesthesia

    When used as a sedative in combined anesthesia, small doses (0.03-0.1 mg / kg) or long-term infusion (0.03-0.1 mg / kg / h) are administered intravenously, usually in combination with analgesics . The dose and intervals between doses vary according to the patient's individual response. In people over 60 years old, depleted or chronically ill patients use lower maintenance doses.

    Long-term sedation in intensive care

    The desired level of sedation is achieved through the gradual administration of midazolam in accordance with clinical need, physical condition, age and concomitant therapy.

    Adults

    Shock dose: intravenously, 0.03-0.3 mg / kg, administered fractional (each increase of 1-2.5 mg administered for 20-30 seconds, with an interval of 2 minutes). In patients with hypovolemia, vasoconstriction, or hypothermia, the shock dose is reduced or eliminated.

    When the drug is administered together with strong analgesics,the latter are administered first, so that the sedative effects of midazolam can safely be superimposed on any sedative effect caused by the analgesic.

    Supportive dose: intravenously, 0.03-0.2 mg / kg / h. Patients with hypovolemia, vasoconstriction or hypothermia dose are reduced.

    Children

    Children older than 6 months undergoing intubation and ventilation of the lung, the impact dose of 0.05-0.2 mg / kg administered intravenously slowly, at least for 2-3 minutes, until the desired clinical effect is established or by intravenous infusion of 0.06- 0.12 mg / kg / h (1-2 μg / kg / min). Newborns and children up to 6 months of age - by continuous intravenous infusion, starting at 0.03 mg / kg / h (0.5 μg / kg / min) for infants with gestational ages less than 32 weeks or 0.06 mg / kg / hour (1 mkg / kg / min) for newborns with a gestational age of more than 32 weeks and children up to 6 months. The introduction of a shock dose is not recommended, you can increase the infusion rate for the first few hours to achieve a therapeutic concentration in the plasma.

    Special patient groups

    Renal failure. In patients with renal insufficiency (creatinine clearance <10 ml / min), the pharmacokinetics of midazolam after a single intravenous administration is comparable to that of healthy volunteers.After a prolonged infusion in the intensive care unit, the average duration of sedation in patients with renal insufficiency, however, was significantly higher, probably due to the accumulation of α-hydroxymidazolamglucuronide.

    Data on the use of midazolam in patients with severe renal insufficiency (creatinine clearance <30 ml / min) are absent.

    Liver failure. In patients with hepatic insufficiency, the hepatic clearance of midazolam decreases (with subsequent increase in its T1/2), in connection with which its clinical effect can be more pronounced and prolonged. Therefore, a reduction in the dose of midazolam and monitoring of vital body functions is required.

    Side effects:

    The frequency of adverse reactions was determined in accordance with the recommendations of the World Health Organization: very often (≥ 1:10), often (≥1: 100, <1:10), infrequently (≥ 1: 1000, <1: 100), rarely (≥ 1: 10000, <1: 1000), very rarely (<1: 10000), the frequency is unknown (can not be estimated from the available data).

    Allergic reactions (frequency unknown): generalized hypersensitivity reactions (skin, cardiovascular, bronchospasm), anaphylactic shock.

    Mental disorders (frequency unknown): confusion, euphoria, hallucinations, delirium; paradoxical reactions - agitation, involuntary movements (including tonic-clonic movements, tremor), hyperactivity, hostility, aggressiveness, paroxysmal anxiety (especially in children and the elderly); development of mental dependence; syndrome "cancellation" with a sharp withdrawal of the drug.

    From the nervous system (frequency unknown): drowsiness and prolonged sedation, decreased concentration of attention, headache, dizziness, ataxia, anterograde amnesia, seizures (in premature infants and newborns).

    From the side of the cardiovascular system (frequency unknown): cardiac arrest, lowering of blood pressure, bradycardia, vasodilation (the probability of life-threatening conditions is higher in people over 60 years old and in patients with concomitant diseases of the cardiovascular and respiratory system, especially against the background of rapid administration of the drug or the use of high doses).

    From the respiratory system (frequency unknown): respiratory depression, apnea, respiratory arrest, shortness of breath,laryngospasm (the probability of life-threatening conditions is higher in people over 60 years old and in patients with concomitant diseases of the cardiovascular and respiratory systems, especially against the background of rapid administration of the drug or the use of high doses).

    From the gastrointestinal tract (frequency unknown): nausea, vomiting, hiccough, constipation, dry mouth.

    Overdose:

    Symptoms: dizziness, ataxia, dysarthria, nystagmus. Overdose rarely leads to life-threatening conditions, but there may be areflexia, dyspnea, muscle hypotension, oppression of cardiovascular and respiratory activity, coma. Symptoms of overdose usually last for several hours, but may be longer, especially in the elderly, in whom they can be cyclical. In patients with concomitant diseases of the respiratory system, respiratory disorders occur in a more severe form.

    Benzodiazepine derivatives can enhance the effect of other drugs that depress the central nervous system, including alcohol.

    Treatment: artificial lung ventilation, measures aimed at maintaining the activity of the cardiovascular system.

    In case of severe intoxication accompanied by coma or respiratory depression, a benzodiazepine receptor antagonist is prescribed - flumazenil. It should be used with caution in case of mixed overdose, in patients with epilepsy who have already taken benzodiazepine derivatives; with extreme caution in patients who previously received therapy with drugs that reduce the threshold of convulsive readiness (eg, tricyclic antidepressants) or in patients with abnormalities on the ECG (QRS complex extension and QT interval prolongation).

    For more details, refer to the instructions for using flumazenil.

    Interaction:

    Pharmacokinetic interactions

    Midazolam is metabolized by the isoenzyme CYP3A4, so inductors and inhibitors of the latter can reduce or increase the concentration of midazolam in the plasma. With parenteral administration, the effect of the CYP3A4 isoenzyme on the midazolam concentration in the plasma is lower (due to the absence of the "first pass" effect through the liver) and is due only to the systemic clearance of the latter.

    With a single application of midazolam and an inhibitor of the isoenzyme CYP3A4, the duration of midazolam does not change in practice,However, with long-term administration of midazolam, this effect manifests itself in full and causes an increase in the magnitude and duration of midazolam.

    Therefore, it is recommended to monitor the clinical effect and vital functions while using midazolam and inhibitors of the isoenzyme CYP3A4. Administration of midazolam at higher doses or as a prolonged infusion in intensive care units against the background of inhibitors of the isoenzyme CYP3A4 can lead to a prolonged sedation effect and a prolonged recovery of the depressed breathing, and therefore a dose adjustment of midazolam is required. To maximize the induction of CYP3A4 isoenzyme activity, several days of continuous use of its inducers are required, the activity of the induced isoenzyme CYP3A4 decreases for several days. It is believed that the short-term use of CYP3A4 isoenzyme inducers practically does not affect the pharmacokinetics of midazolam.

    Interaction with inhibitors of the isoenzyme CYP3A4

    Antifungal drugs - derivatives of azole. With the simultaneous use of ketoconazole, the concentration of midazolam in plasma increases fivefold, T1/2 - 3 times, so you should take extra care with the simultaneous use of ketoconazole and midazolam and apply this combination only in settings in which a patient can establish a vigilant control. Voriconazole increases the concentration in the plasma and T1/2 midazolam in 3 times. Itraconazole and fluconazole increase the concentration of midazolam in plasma by 2-3 times, itraconazole increases T1/2 midazolam 2.4 times, fluconazole - in 1,5 times. Posaconazole increases the concentration of midazolam in plasma by 2 times.

    Antibiotics-macrolides. Erythromycin increases the concentration of midazolam in plasma 1.6-2 times, T1/2 - in 1,5-1,8 times. Clarithromycin increases the concentration of midazolam in plasma by 2.5 times, T1/2 - 1,5-2 times.

    HIV protease inhibitors. HIV protease inhibitors (including saquinavir, ritonavir, lopinavir) significantly increase the concentration of midazolam in plasma (up to 5.4 times) and its T1/2. When these medications are used together with midazolam, the recommendations described for antifungal agents - azole derivatives - should be followed.

    Blockers of "slow" calcium channels. A single dose of diltiazem increases the concentration of midazolam in plasma by 25% and its T1/2 on 43%.

    Interaction with other drugs. At simultaneous application with atorvastatinum concentration of midazolam in plasma increases in 1,4 times.

    Interaction with inducers of isoenzyme CYP3A4

    Rifampcin. The seven-day course of rifampicin at a dose of 600 mg / day reduces the concentration of midazolam in plasma by 40% and its T1 / 2 by 50-60%.

    Saint John's wort. With the simultaneous application of St. John's wort, the concentration of midazolam in the plasma is reduced by 20-40%, and its T1/2 by 15-17%, which depends on the concentration of St. John's wort extract.

    Pharmacodynamic interactions

    With the simultaneous use of midazolam with other drugs that depress the central nervous system, including alcohol, narcotic analgesics, neuroleptics, other benzodiazepine derivatives, barbiturates, propofol, ketamine, etomidate, antidepressants with sedative effect, H blockers1 -gistaminovyh receptors of the first generation, central hypotensive agents, etc., CNS depression is intensified.

    The simultaneous use of midazolam and the use of alcohol should be avoided.

    Midazolam reduces the minimum alveolar concentration of inhaled anesthetics.

    Special instructions:

    Midazolam should be used only by specialists trained in the method of its administration, and also capable of providing resuscitative care, the necessity of which can arise when some unwanted drug drug reactions occur. With the use of midazolam, serious adverse drug reactions have been reported, including respiratory depression, apnea, respiratory arrest, and / or cardiac arrest. The likelihood of such life-threatening conditions is higher with a high rate of administration or a high dose of the drug. Particular caution should be exercised when used as sedation in patients with impaired breathing function.

    Children under the age of 6 months are particularly susceptible to airway obstruction and hypoventilation, so in these cases, the dose is increased gradually until the clinical effect is achieved, carefully monitoring the respiratory rate and oxygen saturation of the blood.

    When using midazolam for premedication, the patient should be under constant monitoring, as there is a risk of overdose with other drugs.

    Particular caution should be exercised when assigning midazolam to specific patient groups:

    - Patients over 60 years of age;

    - Patients with severe general condition or chronic diseases (eg, chronic respiratory failure, chronic renal failure, hepatic or heart failure);

    - Children, especially with concomitant cardiovascular diseases. The dose in such patients should be reduced, and they should be under constant monitoring for deterioration of vital functions. Caution should be exercised when benzodiazepines are prescribed to patients with alcoholism or drug addiction (including history).

    As with other drugs, depressing the central nervous system and (or) possessing muscle relaxant properties, caution should be exercised when using midazolam in patients with myasthenia gravis.

    Addiction

    There are reports of some loss of efficiency when midazolam was administered for prolonged sedation in intensive care units.

    Addiction

    With long-term use of midazolam (long-term sedation in intensive care units), a physical

    addiction. Its risk increases with increasing dose and duration of treatment, it is also higher in patients with alcoholism and (or) drug addiction in the history.

    Withdrawal of symptoms

    During long-term treatment with midazolam in the intensive care unit, the development of psychophysical dependence is possible. Thus, with the sudden cancellation of treatment, withdrawal may develop, which can be manifested by the following symptoms: headache, muscle pain, anxiety, tension, agitation, confusion, irritability, "ricochet" insomnia, mood swings, hallucinations and convulsions. To avoid the syndrome of "cancellation," it is recommended that the dose be gradually reduced until it is discontinued.

    Amnesia

    Midazolam may cause anterograde amnesia (often a desirable effect, for example, before and during surgical and diagnostic procedures), the duration of which is directly proportional to the dose administered. For ambulatory patients discharged immediately after the operation, prolonged amnesia can cause inconvenience, so after parenteral administration of midazolam, the patient should be discharged only accompanied by medical personnel or persons close to him. Paradoxical reactions

    When using midazolam, paradoxical reactions were recorded: agitation,involuntary movements (including tonic-clonic convulsions and muscle tremors), hyperactivity, hostility, outbursts of anger, aggressiveness, paroxysmal anxiety and attacks. These reactions occur with the administration of high doses and (or) with the rapid administration of the drug. The highest frequency of these reactions is observed in children and the elderly.

    Modified Midazolam Activity

    The activity of midazolam may be altered in patients using inducers or inhibitors of the CYP3A4 isoenzyme, so there may be a need for correcting the dose of midazolam (see "Interaction with other drugs").

    Metabolism of midazolam may be slowed in patients with hepatic insufficiency, low cardiac output, and in newborns (see the section "Pharmacokinetics"),

    Preterm and term infants

    Because of the increased risk of developing apnea, it is advisable to exercise extreme caution when used in non-intubated premature or full-term newborns. In these cases, careful monitoring of respiratory rate and oxygen saturation of blood is necessary. Rapid administration of the drug is not recommended.Due to underdevelopment of metabolic functions of newborns, they are also susceptible to respiratory depression. In children with cardiovascular diseases to prevent the worsening of the condition, the drug should be administered slowly.

    Children under 6 months of age

    It is not recommended to use the drug to achieve sedation and premedication in children younger than 6 months.

    Children under the age of 6 months are particularly susceptible to airway obstruction and hypoventilation, so increase the dose in small steps. In addition, careful monitoring of the respiratory rate and oxygen saturation of blood is necessary (see also subsection "Premature and full-term newborns").

    In children younger than 6 months, as well as with a body weight of less than 15 kg, the use of a solution with a concentration above 1 mg / ml is not recommended. Higher concentrations should be diluted to 1 mg / ml.

    When used in children's practice, it must be remembered that intramuscular injection is painful.

    Simultaneous use of alcohol and (or) drugs that oppress the central nervous system. It is necessary to avoid the simultaneous use of midazolam with alcohol or drugs that depress the central nervous system.Such use may increase the clinical effects of midazolam and lead to severe sedation or clinically significant respiratory depression (see "Interactions with Other Drugs" section).

    Alcoholism or drug addiction

    In patients with alcoholism or drug addiction, a history of midazolam and other benzodiazepine derivatives should be avoided.

    Extract from the treatment and prophylactic institution

    After the completion of the necessary procedures the patient should be observed until the full restoration of consciousness and motor abilities, the patient must be discharged in the company of persons close to him.

    The drug contains 3.16 mg / ml sodium, which may be important for patients on a hyponatrial diet.

    During the treatment period, you can not take ethanol, especially in the first 6 hours after taking the drug.

    Effect on the ability to drive transp. cf. and fur:Sedation, amnesia, reduced concentration of attention, impaired muscle function have a negative effect on the ability to drive a car or work with mechanisms. Do not drive vehicles or work with machines and mechanisms until the effect of the drug is completely eliminated.The resumption of such activities should take place with the permission of the attending physician.
    Form release / dosage:Solution for intravenous and intramuscular injection 5 mg / ml.
    Packaging:

    1 ml of the drug in a vial of colorless glass, hydrolytic type 1 with a blue break point. For 5 or 10 ampoules (in plastic pallets of 5 pieces) with instructions for use in a cardboard bundle.

    For 3 ml of the drug in a vial of colorless glass, hydrolytic type 1 with a blue break point. For 5 or 10 ampoules (in plastic pallets of 5 pieces) with instructions for use in a cardboard bundle.

    Storage conditions:

    In accordance with the rules for storage of psychotropic substances listed in List III of the "List of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation".

    In the dark place at a temperature of no higher than 25 ° C.

    Do not freeze.

    In a place inaccessible to children.

    Shelf life:

    3 years.

    Do not use after the expiration date printed on the package. The contents of the ampoule are used immediately after opening, the unused portion is not subject to storage.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-002437
    Date of registration:22.04.2014
    Expiration Date:22.04.2019
    Manufacturer: & nbsp
    Information update date: & nbsp24.04.2018
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