Dormicum solution: instructions for use. Medicinal reference book geotar Dormicum higher single and daily doses

Dormicum is a sedative that has an anxiolytic, hypnotic, anticonvulsant and muscle relaxant effect.

Release form and composition

Dormicum solution is produced in the form of a colorless transparent liquid, in colorless glass ampoules of 1 and 3 ml. The composition of one 1 ml ampoule includes 5 mg of midazolam and excipients - hydrochloric acid, sodium chloride, water for injection and sodium hydroxide.

Indications for use

Dormicum is used for premedication before induction anesthesia, conscious sedation before or during medical or diagnostic procedures performed under local anesthesia or without it.

For adults, Dormicum is prescribed as an induction anesthesia, as well as a sedative component in combined anesthesia, for children - for sedation in intensive care.

Contraindications

The use of Dormicum is contraindicated in case of hypersensitivity to the components that make up its composition, as well as in cases of:

• Acute respiratory failure;
• coma;
• Acute alcohol intoxication with suppression of vital functions;
• Shock;
• Angle-closure glaucoma;
• Acute pulmonary insufficiency;
• the period of childbirth;
• Chronic obstructive pulmonary disease.

With caution, Dormicum is prescribed to patients over 60 years of age, premature babies, newborns under six months, as well as heart and respiratory failure, extremely serious condition, myasthenia gravis, impaired liver and kidney function.

Method of application and dosage

The solution is administered intravenously slowly. The dosage of Dormicum is determined strictly on an individual basis. To safely achieve the desired sedative effect, corresponding to the age, physical condition and clinical needs of the patient, it is recommended to titrate the dose of the drug.

In cases of conscious sedation in adults, the drug is administered at a rate of 1 mg per half minute.

The initial dose of Dormicum for patients aged 13 to 60 years is 2-2.5 mg, with a possible repeated administration of 1 mg of the drug. Patients over 60 years of age are prescribed 0.5-1 mg of solution, children 6-12 years old - 0.025-0.05 mg / kg, children from six months to 5 years - 0.05-0.1 mg / kg. The agent is administered 5-10 minutes before the start of sedation.

For children aged 1 to 16 years, Dormicum is also administered intramuscularly at a dose determined on the basis of the calculation - 0.05-0.15 mg of solution per 1 kg of body weight.

Side effects

The instructions for Dormicum indicate that the drug can cause side effects from some body systems, namely:

• Headache, anterograde or retrograde amnesia, drowsiness, prolonged sedation, dizziness, paresthesia, ataxia, sleep disturbance, anxiety, decreased concentration, athetoid movements, delirium, slurred speech and dysphonia (central and peripheral nervous system);
• Anaphylactic shock and generalized hypersensitivity reactions (immune system);
• Hallucinations, confusion and euphoria (psychic);
• Tachycardia, hypotension, bigeminia, bradycardia, vasovagal crisis, vasodilation, premature ventricular contraction and rhythm from the atrioventricular junction (cardiovascular system);
• Nausea, constipation, vomiting, sour taste and dry mouth, belching and salivation (gastrointestinal tract);
• Urticaria, itching and skin rash (skin and subcutaneous fat).

Dormicum can cause pain and erythema at the injection site, thrombosis, thrombophlebitis, as well as adverse reactions from the respiratory and sensory organs, namely:

• Respiratory depression, hyperventilation, apnea, hiccups, laryngospasm, airway obstruction, bronchospasm, tachypnea, and respiratory arrest;
• Double vision, pupillary constriction, refractive error, nystagmus, impaired and worsening visual acuity, periodic twitching of the eyelids, loss of balance, fainting and congestion in the ears.

Symptoms of an overdose of Dormicum are a decrease in blood pressure, areflexia, depression of cardiorespiratory activity, apnea and coma.

In such cases, it is required to monitor vital signs and, if necessary, conduct maintenance therapy.

special instructions

It is important to bear in mind that with the parenteral use of Dormicum, inhibition of myocardial contractility and respiratory arrest may occur. In this regard, it is recommended to use the drug only in the presence of resuscitation equipment.

In cases of prolonged intravenous use of the drug, it is recommended to cancel Dormicum gradually. This is due to the fact that with a sharp withdrawal of the drug, the patient may develop withdrawal symptoms.

During the period of drug therapy, alcohol and drugs that depress the central nervous system should not be consumed.

Analogues

Synonyms of the drug are Fulsed and Midazolam-hameln. Dormicum's analogues include Flunitrazepam-Ferein and Nitrazepam.

Terms and conditions of storage

In accordance with the instructions, Dormicum should be stored in a place protected from light, dry and out of the reach of children, at a temperature not exceeding 30 ºС.

From pharmacies, the drug is dispensed by prescription. The shelf life of the solution, subject to the manufacturer's recommendations, is five years.

The instructions for use of the drug Dormicum indicate that it is a drug with a hypnotic and sedative effect. It is widely used in medical practice for premedication before surgery and for sedation during prolonged intensive care.

Composition and action of Dormicum

One milliliter of the solution contains 5 mg of the active substance midazolam. In tablets, there are 7.5 or 15 mg of midazolam. Hydrochloric acid and water are isolated as auxiliary components.

The drug is available as a solution, ampoules of 1 ml and 3 ml. The liquid has no color, is transparent without any inclusions. Ampoules Dormicum are packed in a cardboard box with contour cells. Tablets are issued in blisters.

The drug has anxiolytic, myoreoaxic, anticonvulsant and hypnotic effects. It belongs to the group of benzodiazepine drugs with a short mechanism of action. The imidobenzodiazepine group, which includes Dormicum, stimulates GABA receptors located in the brain.

Due to the connection with benzodiazepine receptors, the excitability of subcortical structures decreases. Due to this effect, its pharmacological effect on the body is achieved. Due to the reaction with different receptors, there is a difference in action: some are responsible for sedation and anticonvulsant effect, others for anxiolytic activity and muscle relaxation.

The drug, when administered intramuscularly, undergoes rapid absorption almost in full. In liver cells, it breaks down to form inactive substances. The drug is able to penetrate not only through the cerebrospinal fluid, but also through the placenta and breast milk.
Inactive metabolic products are excreted in bile or urine. In this case, it is necessary to take into account some features of the metabolism of Dormicum:

1. The elimination half-life increases in obese patients, liver and kidney diseases, as well as in older and pediatric patients.
2. With parenteral administration, anterograde amnesia may occur.
3. The fastest is the sedative and hypnotic effects.
4. The average elimination half-life in a healthy person is 2 hours.

Indications and contraindications for use

Among the main indications for the use of Dormicum are:

1. Achieving sedation of the patient in order to reduce arousal before conducting invasive diagnostics and surgical interventions.
2. Performing induction anesthesia, as well as an element of preliminary preparation for anesthesia.
3. Prolonged sedation for critically ill patients requiring intensive care.
4. For children, Dormicum is used as an element of sedation in preparation for anesthesia, as well as achieving a similar effect in a serious condition.

Dormicum is prohibited to use if the patient has:

1. Sensitization to drugs belonging to the class of benzodiazepines.
2. Insufficiency of pulmonary ventilation, as well as severe diseases of the respiratory system.
3. Coma, shock or impaired consciousness on the background of alcohol intoxication with the manifestation of depression of vital functions.
4. Angle-closure glaucoma.
5. Obstruction of lung tissue.
6. During childbirth.

Particular care should be taken when:

• prematurity of the newborn;
• advanced age;
• severe insufficiency of vital systems;
• children up to six months.

The development of side effects is possible in case of violation of the dosing regimen, neglect of contraindications, as well as the presence of individual hypersensitivity of the organism. Among the most common negative actions are:

1. Allergic reaction with anaphylactic shock.
2. Malfunctions of the nervous system with euphoria, impaired consciousness, clonic-tonic convulsions and aggression.
3. If Dormicum is used for a long time, addiction may develop. More often it is faced by patients with addiction to alcohol or drugs. Abrupt discontinuation of the drug leads to the appearance of a withdrawal syndrome.
4. , the development of postoperative drowsiness, as well as anterograde and retrograde.
5. Patients with pathology of the heart and blood vessels are faced with hypotension, a decrease in heart rate up to complete cardiac arrest.

Instructions for use

The drug has features of use. It must be remembered that the introduction should be carried out slowly. The dosage is selected individually, taking into account the patient's condition, age, weight and other factors. When administered, the dosage is titrated to monitor the therapeutic effect. To achieve a long-term result, an additional administration of a maintenance dose is carried out.

The development of an overdose is possible against the background of a slight excess of the therapeutic amount. Among the symptoms of intoxication, the appearance of hypotension, areflexia, apnea, and violations of vital functions with a possible one are noted.

In this case, blood pressure and respiration are controlled. If necessary, symptomatic treatment is prescribed. Emergency assistance consists in the use of adsorbents. The therapeutic effect is possible if the drug was taken orally no earlier than 2 hours. Anexat is shown as a drug that exhibits antagonistic properties.

Read: varieties of remedies, their benefits and harms, withdrawal syndrome.

Learn on the human body.

All sleeping pills and contraindications to the appointment.

Terms of sale and cost of Dormicum

The price of the drug Dormicum averages 550-700 rubles. It is dispensed by prescription, but it is difficult to get it in the pharmacy network, since the medicine is delivered mainly to medical institutions. The tool does not require special conditions for storage, it is not recommended only to allow temperature differences, as well as exposure to direct sunlight. The drug is allowed to use 5 years from the date of manufacture.

Dormicum received good reviews from doctors, as did its counterparts Nitrazepam and Rohypnol. However, due to the high risk of side effects and overdose, strict medical control of the condition is provided when prescribing the drug. Do not use on your own at home.

Catad_pgroup Anxiolytics (tranquilizers)

Dormicum - instructions for use

INSTRUCTIONS
on the medical use of the drug

Registration number: P No. 016119/01

Trade name of the drug
DORMIKUM (DORMICUM ®)

International non-proprietary name
Midazolam (Midazolam)

chemical name
8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo benzodiazepine

Dosage form
Solution for intravenous and intramuscular administration

Compound
1 ml (1 ampoule) contains: midazolam 5 mg
3 ml (1 ampoule) of the drug contains: midazolam 15 mg
Excipients: sodium chloride, hydrochloric acid, sodium hydroxide, water for injection

Description
Clear colorless or slightly yellowish liquid.

Pharmacotherapeutic group
sleeping pill

ATX code

Pharmacological properties
Short-acting benzodiazepine for premedication, sedation, induction and main anesthesia
The active substance Dormicum - midazolam - belongs to the group of imidobenzodiazepines. The free base is a lipophilic substance, poorly soluble in water.
The presence of a basic nitrogen atom in position 2 of the imidobenzodiazepine ring allows midazolam to form water-soluble salts with acids, which give stable and well-tolerated injection solutions.
The pharmacological action of the drug is characterized by a rapid onset and - due to rapid biotransformation - a short duration. Due to its low toxicity, midazolam has a large therapeutic window.
Dormicum has a very fast sedative and pronounced hypnotic effect. It also has anxiolytic, anticonvulsant and muscle relaxant effects.
After parenteral administration, a short anterograde amnesia occurs (the patient does not remember the events that occurred during the period of the most intense action of the active substance).

Pharmacokinetics
Absorption after intramuscular injection
Midazolam is absorbed from muscle tissue quickly and completely. The maximum plasma concentration is reached within 30 minutes. Absolute bioavailability after intramuscular injection exceeds 90%.
Distribution
After intravenous administration, the midazolam plasma concentration curve is characterized by one or two well-defined distribution phases. The volume of distribution in the equilibrium state is 0.7-1.2 l / kg of body weight. The degree of binding to plasma proteins is 96-98%, mainly to albumin. Midazolam passes into the cerebrospinal fluid slowly and in small amounts. Midazolam slowly crosses the placental barrier and enters the fetal circulation; small amounts are found in breast milk.
Metabolism
Midazolam is eliminated almost exclusively by biotransformation. Less than 1% of the dose taken is found in the urine as unchanged drug. Midazolam is hydroxylated by the 3A4 isoenzyme of the cytochrome P450 system. The main metabolite in plasma and urine is a-hydroxymidazolam. 60-80% of the dose received is excreted in the urine as a-hydroxymidazolam glucuronide. Plasma concentrations of a-hydroxymidazolam are 12% of those of the parent substance. The effect of the first passage through the liver reaches 30-60%. The half-life of the metabolite is less than 1 hour. α-Hydroxymidazolam has pharmacological activity, but only to a minimal extent (about 10%) causes the effects of intravenously administered midazolam. There are no data on the role of genetic polymorphism in the oxidative metabolism of midazolam.
breeding
In healthy volunteers, the half-life is 1.5-2.5 hours. Plasma clearance is 500 ml / min. If midazolam is administered intravenously by drip, the kinetics of its excretion does not differ from that after a jet injection.
Pharmacokinetics in special groups of patients
In patients older than 60 years, the half-life can increase up to 4 times.
In children aged 3 to 10 years, the half-life after intravenous administration is shorter than in adults, which corresponds to an increased metabolic clearance of the drug.
In newborns - possibly due to the immaturity of the liver - the half-life is increased and averages 6-12 hours, and the clearance of the drug is slowed down.
The half-life of the drug in patients with cirrhosis of the liver may be prolonged, and the clearance may decrease, compared with similar indicators in healthy volunteers.
The half-life of the drug in patients with chronic renal failure is similar to that in healthy volunteers.
In critically ill patients, the half-life of midazolam is increased.
In congestive heart failure, the half-life of midazolam is also longer than in healthy individuals.

Indications
Conscious sedation before diagnostic or therapeutic procedures, performed under local anesthesia or without it (intravenous administration).
Premedication before induction anesthesia (intramuscularly in children).
Introductory and maintenance anesthesia. As an induction agent for inhalation anesthesia or as a sedative component for combined anesthesia, including total intravenous anesthesia (intravenous bolus and drip).
Ataralgesia in combination with ketamine in children (intramuscularly).
Long-term sedation in intensive care (intravenous stream or drip).

Contraindications
Hypersensitivity to benzodiazepines or to any component of the drug.

Pregnancy and lactation
There are insufficient data to assess the safety of midazolam in pregnancy.
Benzodiazepines should not be used during pregnancy unless there is a safer alternative. The administration of the drug in the last trimester of pregnancy or in high doses during the first stage of labor leads to cardiac arrhythmias in the fetus, hypotension, impaired sucking, hypothermia and mild respiratory depression in the newborn. Moreover, children whose mothers received long-term benzodiazepines in the later stages of pregnancy may develop physical dependence with a certain risk of withdrawal syndrome in the postnatal period.
Since midazolam passes into breast milk, Dormicum should not be used in nursing mothers.

Mode of application
Midazolam is a strong sedative that requires slow administration and individual dose selection.
The dose should be titrated until the desired sedative effect is achieved, which corresponds to the clinical need, the physical condition and age of the patient, as well as the drug therapy received by him.
In patients over 60 years of age, debilitated or chronic patients, the dose should be selected carefully, taking into account the special factors inherent in each patient.
Conscious intravenous sedation
The dose of Dormicum is selected individually; the drug should not be administered quickly or in a stream. The onset of sedation varies individually, depending on the patient's condition and dosing regimen (rate of administration, dose size). If necessary, the dose is selected individually. The effect occurs approximately 2 minutes after administration, the maximum - on average, after 2.4 minutes.
adults
Dormicum should be administered intravenously slowly, at a rate of approximately 1 mg per 30 seconds. For adult patients under the age of 60, the initial dose is 2.5 mg 5-10 minutes before the start of the procedure. If necessary, enter subsequent doses of 1 mg. Average total doses range from 3.5 to 7.5 mg. Usually a total dose not exceeding 5 mg is sufficient.
For patients over 60 years of age, debilitated or chronically ill, the initial dose is reduced to approximately 1 mg and administered 5-10 minutes before the start of the procedure. If necessary, enter subsequent doses of 0.5-1 mg. Since in these patients the maximum effect may not be achieved so quickly, subsequent doses should be titrated very slowly and carefully. Usually a total dose not exceeding 3.5 mg is sufficient.
Children
Intramuscularly, the drug is administered at a dose of 0.1-0.15 mg/kg 5-10 minutes before the procedure. Patients in a state of more pronounced excitation can be administered up to 0.5 mg / kg of body weight. Usually a total dose not exceeding 10 mg is sufficient.
Intravenously, the initial dose of Dormicum is administered over 2-3 minutes, after which, before proceeding with the procedure or administering a second dose, you need to wait another 2-3 minutes to assess the sedative effect. If sedation needs to be increased, continue to carefully titrate the dose until the desired degree of sedation is achieved. Infants and children under 5 years of age may require much larger doses than older children and adolescents.
Data on non-intubated children under 6 months of age are limited. These children are particularly prone to airway obstruction and hypoventilation, so it is essential to titrate the dose in small increments until clinical benefit is achieved, and to closely monitor patients.
The initial dose in children from 6 months to 5 years is 0.05 - 0.1 mg / kg. To achieve the desired effect, a total dose of up to 0.6 mg / kg may be required, but it should not exceed 6 mg.
The initial dose in children from 6 to 12 years old is 0.025 - 0.05 mg / kg, the total dose is up to 0.4 mg / kg (no more than 10 mg).
Doses for children 12 to 16 years of age are the same as for adults.
anesthesia
Premedication
Premedication with Dormicum shortly before the procedure has a sedative effect (the onset of drowsiness and the elimination of emotional stress), and also causes preoperative amnesia. Premedication is usually performed by injecting the drug deep into the muscle 20-60 minutes before induction of anesthesia.
Dormicum can be used in combination with anticholinergics.
Intramuscular administration
Adults: For preoperative sedation and memory elimination of preoperative events, patients who are not at high risk (ASA class 1 or II, under 60 years of age) are administered 0.07-0.1 mg/kg body weight (about 5 mg).
Patients over 60 years of age, debilitated or chronic: the dose is individually reduced. If the patient is not simultaneously taking drugs, the recommended dose of midazolam is 0.025 - 0.05 mg / kg, the usual dose is 2-3 mg. In patients over 70 years of age, intramuscular administration of Dormicum should be carried out carefully, under continuous supervision, because of the possibility of excessive drowsiness.
Children from 1 to 15 years: relatively higher doses (per kg of body weight) than adults. Doses in the range of 0.08-0.2 mg/kg have proven to be effective and safe.
Induction anesthesia (adults)
If Dormicum is administered for induction anesthesia before other anesthetics, then the individual response of patients varies greatly. The dose should be titrated to the desired effect in accordance with the age and clinical condition of the patient. If Dormicum is administered before other intravenous induction drugs, then the initial doses of each of these drugs can be significantly reduced, sometimes up to 25% of the standard initial dose.
The desired level of anesthesia is achieved by dose titration. The induction dose of Dormicum is administered intravenously slowly, fractionally. Each repeated dose not exceeding 5 mg should be administered within 20-30 seconds, with intervals of 2 minutes between injections.
Adult patients under 60 years of age: a dose of 0.15-0.2 mg / kg is administered intravenously over 20-30 seconds, after which you should wait 2 minutes to evaluate the effect. For surgical patients of senile age who do not belong to the high-risk group (ASA class I and II), an initial dose of 0.2 mg / kg is recommended. In some debilitated patients or patients with severe comorbidities, a lower dose may be sufficient.
Adult patients under 60 years of age who have not received premedication: the dose may be higher, up to 0.3-0.35 mg / kg body weight. It is administered intravenously over 20-30 seconds, after which you should wait 2 minutes to evaluate the effect. If necessary, to complete the induction, the drug is administered additionally in doses of about 25% of the initial one. Alternatively, liquid inhalational anesthetics can be used to complete the induction. In refractory cases, the induction dose of Dormicum may reach 0.6 mg/kg, but recovery of consciousness after such doses may be delayed.
Patients over 60 years of age who have not received premedication require smaller induction doses of Dormicum; the recommended initial dose is 0.3 mg/kg, for patients with severe comorbidities and debilitated patients, an induction dose of 0.2-0.25 mg/kg is sufficient, sometimes only 0.15 mg/kg.
For induction anesthesia in children, Dormicum is not recommended, since the experience of its use is limited.
Maintenance anesthesia
Maintaining the desired level of consciousness off can be achieved either by further fractional administration of small doses (0.03-0.1 mg / kg), or by continuous intravenous infusion at a dose of 0.03 - 0.1 mg / kg x hour, usually in combination with analgesics. Doses and intervals between injections depend on the individual response of the patient.
Patients over 60 years of age, debilitated or chronically ill require smaller doses to maintain anesthesia.
Children receiving ketamine for the purpose of anesthesia (ataralgesia) are recommended to administer a dose of 0.15 to 0.20 mg / kg intramuscularly. Sufficiently deep sleep is usually achieved in 2-3 minutes.
Intravenous sedation in intensive care
The desired sedative effect is achieved by gradual dose selection, followed by either continuous infusion or fractional jet administration of the drug, depending on the clinical need, the patient's condition, age and simultaneously administered drugs.
adults
An intravenous loading dose is administered fractionally, slowly. Each repeated dose of 1-2.5 mg is administered over 20-30 seconds, observing 2-minute intervals between injections.
The intravenous loading dose can range from 0.03-0.3 mg/kg, with a total dose of no more than 15 mg usually sufficient.
In patients with hypovolemia, vasoconstriction or hypothermia, the loading dose is reduced or not administered at all.
If Dormicum is used simultaneously with strong analgesics, the latter should be administered before it, so that the dose of Dormicum can be safely titrated at the height of sedation caused by the analgesic.
The maintenance dose can be 0.03-0.2 mg / (kg x hour). In patients with hypovolemia, vasoconstriction or hypothermia, the maintenance dose is reduced. If the patient's condition allows, the degree of sedation should be regularly assessed.
Children
To achieve the desired clinical effect, the drug is administered intravenously at a dose of 0.05-0.2 mg / kg for at least 2-3 minutes (it should not be administered intravenously quickly). After that, they switch to continuous intravenous infusion at a dose of 0.06-0.12 mg / kg (1-2 mcg / kg / min). If necessary, to enhance or maintain the desired effect, the infusion rate can be increased or decreased (usually by 25% of the initial or subsequent rate) or additional doses of Dormicum can be administered.
If Dormicum infusion is started in patients with hemodynamic disturbances, the usual loading dose should be titrated in small "steps", monitoring hemodynamic parameters (hypotension). These patients have a tendency to respiratory depression with Dormicum and require careful monitoring of respiratory rate and oxygen saturation.
Newborns (32 weeks) - at a dose of 0.06 mg / kg / hour (1 mcg / kg / min). An intravenous loading dose is not administered to newborns, instead, the infusion is carried out somewhat faster in the first few hours to achieve therapeutic plasma concentrations of the drug. The infusion rate should be reviewed frequently and carefully, especially during the first 24 hours, to ensure that the lowest effective dose is administered and to reduce the possibility of drug accumulation.
Special, dosing instructions
Dormicum solution in ampoules can be diluted with 0.9% sodium chloride solution, 5% and 10% glucose solution, 5% fructose solution, Ringer's solution and Hartmann's solution in a ratio of 15 mg of midazolam per 100-1000 ml of infusion solution. These solutions remain physically and chemically stable for 24 hours at room temperature or 3 days at 5°C (see also "Special Notes").
Dormicum should not be diluted with a 6% solution of Macrodex in glucose or mixed with alkaline solutions.
In addition, a precipitate may form, which dissolves on shaking at room temperature.

Interaction with other drugs
The metabolism of midazolam is mediated mainly by the isoenzyme of the cytochrome P4503A4 (CYP3A4) system. About 25% of the total activity of the cytochrome 450 system in the liver of adults falls on the CYP3A4 subclass. Inhibitors and inducers of this isoenzyme may interact with midazolam.
Interaction studies conducted with Dormicum solution
Itraconazole and fluconazole. Co-administration of midazolam and itraconazole or fluconazole prolongs the half-life of midazolam from 2.9 to 7.0 hours (itraconazole) or to 4.4 hours (fluconazole). When midazolam is given as a bolus for short-term sedation, itraconazole and fluconazole do not enhance its effects to a clinically significant extent, so dose adjustment is not required. However, when prescribing midazolam in high doses, dose adjustment may become necessary. Long-term infusion of midazolam in patients receiving systemic antimycotics (eg, in intensive care) may prolong the hypnotic effect of the drug if the dose is not titrated according to the effect.
Erythromycin. The simultaneous appointment of Dormicum and erythromycin lengthens the half-life of midazolam from 3.5 to 6.2 hours. Although the observed changes in pharmacodynamics were relatively small, it is recommended to adjust the dose of intravenously administered midazolam, especially when prescribing large doses.
Cimetidine and ranitidine. Cimetidine increases the equilibrium plasma concentrations of midazolam by 26%, while ranitidine does not affect them. The simultaneous administration of midazolam and cimetidine or ranitidine does not have a clinically significant effect on the pharmacokinetics and pharmacodynamics of midazolam. Midazolam can be administered intravenously at normal doses simultaneously with cimetidine and ranitidine.
Cyclosporine. There is no pharmacokinetic and pharmacodynamic interaction between cyclosporine and midazolam; dose adjustment of midazolam when used simultaneously with cyclosporine is not required.
Nitrendipine does not affect the pharmacokinetics and pharmacodynamics of midazolam. Both drugs can be administered simultaneously; dose adjustment of midazolam is not required.
Saquinavir. In 12 healthy volunteers, a single intravenous administration of midazolam at a dose of 0.05 mg/kg after 3-5 days of taking saquinavir at a dose of 1200 mg 3 times a day reduced the clearance of midazolam by 56% and increased its half-life from 4.1 to 9.5 hours. Saquinavir only enhanced the subjective sensation of the effect of midazolam (as measured by the visual analogue scale, the item "total effect of the drug"), so patients taking saquinavir can be given intravenous bolus doses of midazolam. With prolonged infusion of midazolam, it is recommended to reduce the initial dose by 50%.
Oral contraceptives did not affect the pharmacokinetics of intramuscularly administered midazolam; these drugs can be used simultaneously without dose adjustment of midazolam.
Other interactions
Sodium valproate displaces midazolam from protein binding, which may enhance the effects of midazolam. Patients with epilepsy receiving sodium valproate may require dose adjustment of midazolam.
In patients receiving antiarrhythmic therapy or regional anesthesia with lidocaine, midazolam does not affect the binding of lidocaine to plasma proteins.
Alcohol may increase the sedative effect of midazolam.
Intravenous administration of Dormicum reduces the minimum alveolar concentrations of halothane required for general anesthesia.
Incompatibility
Dormicum solution in ampoules cannot be diluted with 6% Macrodex solution in glucose solution. Do not mix Dormicum with alkaline solutions, as midazolam precipitates with sodium bicarbonate

Side effects
Central and peripheral nervous system and mental sphere: drowsiness, prolonged sedation, confusion, euphoria, hallucinations, weakness, headache, dizziness, ataxia, anterograde amnesia, the duration of which is directly dependent on the dose. Anterograde amnesia may occur at the end of the procedure, in some cases it lasts longer.
Cases of paradoxical reactions are described, such as agitation, involuntary motor activity (including tonic-clonic convulsions and muscle tremor), hyperactivity, hostile mood, anger and aggressiveness, excitation paroxysms, especially in children and senile patients.
Seizures have been described in premature infants and neonates.
The use of Dormicum, even in therapeutic doses, can lead to the formation of physical dependence. Withdrawal of the drug, especially abruptly after prolonged intravenous use, may be accompanied by withdrawal symptoms, including convulsions.
Gastrointestinal tract: nausea, vomiting, hiccups, constipation, dry mouth.
Cardiovascular system and respiratory organs: in rare cases, severe cardiorespiratory adverse events have developed. They consisted of depression and respiratory arrest and/or cardiac arrest. The likelihood of such life-threatening reactions is higher in adults over 60 years of age and in those with concomitant respiratory failure or heart failure, especially if the drug is administered too quickly or in large doses. In addition, hypotension, slight tachycardia, vasodilation, shortness of breath, and in some cases laryngospasm have been described.
Skin and its appendages: skin rash, urticaria, itching.
Body as a whole: in some cases - reactions of generalized hypersensitivity, from skin to anaphylactoid.
Local reactions: erythema and pain at the injection site, thrombophlebitis, thrombosis.
In elderly patients, after the use of benzodiazepines, the risk of falls and fractures increases.

Overdose
Symptoms of an overdose of Dormicum are expressed mainly in an increase in its pharmacological effects: drowsiness, confusion, lethargy and muscle weakness or paradoxical arousal. As in the case of an overdose of other benzodiazepines, this is not life-threatening, unless the patient has simultaneously received other drugs that depress the central nervous system, including alcohol. More serious symptoms include areflexia, hypotension, cardiovascular and respiratory depression, respiratory arrest, and, rarely, coma.
In most cases, only vital functions need to be monitored. In the treatment of overdose, special attention is occupied by intensive care aimed at maintaining cardiovascular and respiratory activity. Overdose phenomena can be stopped with a benzodiazepine antagonist - Anexat (active substance - flumazenil). Care must be taken when using flumazenil in case); mixed overdose of drugs, as well as in patients with epilepsy treated with benzodiazepines

special instructions
Dormicum for injection should be used only in the presence of resuscitation equipment, since its intravenous administration can inhibit myocardial contractility and cause respiratory arrest.
Particular care is needed for parenteral administration of Dormicum in the high-risk group: over 60 years of age, debilitated and chronic patients suffering from chronic respiratory failure, chronic renal failure, impaired liver function and congestive heart failure, pediatric patients with cardiovascular instability. These high-risk patients require lower doses (see "Method of application") and constant monitoring for the purpose of early detection of violations of vital functions. In elderly patients, after the use of benzodiazepines, the risk of falls and fractures increases.
With extreme caution, benzodiazepines are used in patients who abuse alcohol and drug addicts.
As with any drug that depresses the central nervous system and has a muscle relaxant effect, special care must be taken when administering Dormicum to patients with myasthenia gravis, since they already have muscle weakness.
When using Dormicum for long-term sedation in the intensive care unit, a slight decrease in the effect of the drug has been described. In addition, in such a situation, one should be aware of the possibility of developing physical dependence, the risk of which depends on the dose and duration of use.
Since abrupt withdrawal of Dormicum after prolonged intravenous use may be accompanied by withdrawal symptoms, it is recommended to reduce its dose gradually.
Dormicum causes anterograde amnesia, which is often desirable before and during surgical and diagnostic procedures. Its duration directly depends on the administered dose. Prolonged amnesia can be a problem for patients about to be discharged after a surgical or diagnostic procedure. After parenteral administration of the drug, patients can be released from the hospital or clinic no earlier than 3 hours later and only with accompaniment.
If symptoms appear that suggest a paradoxical reaction, the effect of Dormicum should be evaluated before continuing its administration.
In children with an unstable state of the cardiovascular system and in newborns, rapid intravenous administration of the drug should be avoided. Special care is needed when sedating preterm infants unless they are intubated because of the risk of apnea. In addition, newborns have a tendency to a prolonged and pronounced inhibitory effect of Dormicum on breathing, which is due to their functional immaturity.

Influence on the ability to drive vehicles and work with machines and mechanisms
Sedation, amnesia, impaired concentration and muscle function may adversely affect the ability to drive or use machines. You should not drive vehicles or work with machines or mechanisms until the effect of the drug has completely ceased.

Release form and packaging
1 ml and 3 ml of the drug in colorless glass ampoules (hydrolytic class 1 according to EP). 5, 10 ampoules (1 ml each) or 5, 10, 25 ampoules (3 ml each), together with instructions for use, are placed in a cardboard box.

Storage conditions
Store at a temperature not exceeding 30°C, protected from light. Do not freeze.

Best before date
5 years.
The drug should not be used after the expiration date indicated on the package.

Terms of dispensing from pharmacies
On prescription.

Manufacturer
F. Hoffmann-La Roche Ltd, produced by Seneksi SAS, France
Manufacturer's registered address:
Seneksi CAC, 52, ru Marcel et Jacquies Gaucherbes 94120 Fontenay-sues-Bois, France
Cenexi SAS, 52, rue Marcel et Jacques Gaucher, 94120 Fontenay-sous-Bois, France
Claims of consumers should be sent to the address of the representative office in Moscow:
125445, st. Smolnaya, 24D

Dormicum is a synthetic drug with a pronounced hypnotic and rapid sedative effect.

Pharmacological action of Dormicum

Dormicum is a drug that has a hypnotic, sedative, anticonvulsant, anxiolytic and central muscle relaxant effect.

The active component of Dormicum - midazolam, being a lipophilic substance, has a stimulating effect on GABA ionotropic receptors, which are located in the central nervous system.

Due to the low toxicity, the drug has a large therapeutic interval. The action of Dormicum is characterized by a rapid onset and a short duration.

After the introduction of the drug, a short-term anterograde amnesia is observed, during which the patient does not remember the events occurring during the action of the active substance.

Composition, release form and analogues of Dormicum

Dormicum is produced as a clear solution for injection (intravenous and intramuscular) containing 1 ml of 5 mg of midazolam in 1 ml and 3 ml ampoules.

It is possible to use an analogue of Dormicum for the active substance (Fulsed) or mode of action (Nitrazepam, Flunitrazepam-Fereina).

Indications for use Dormicum

According to the instructions, Dormicum is prescribed for adults for:

• Conscious sedation before and during diagnostic or therapeutic procedures, performed under local anesthesia or without it;
• Introductory anesthesia and premedication before it;
• Long-term sedation in intensive care, as well as a sedative component in combined anesthesia.

Children Dormicum is usually used:

• When conducting sedation with the preservation of consciousness for diagnostic or therapeutic procedures;
• For premedication before induction anesthesia and long-term sedation in intensive care.

Contraindications

Dormicum is not used against the background of:

• Acute respiratory failure;
• Hypersensitivity to the active substance (midazolam) or auxiliary components;
• Acute pulmonary insufficiency;
• Angle-closure glaucoma;
• Shock, coma, acute alcohol and drug intoxication, accompanied by depression of vital functions;
• Chronic obstructive pulmonary disease.

The drug is not used as part of therapy during childbirth. Caution requires the use of Dormicum:

• Elderly people over 60;
• Patients in extremely serious conditions;
• Against the background of respiratory failure;
• Against the background of dysfunction of the kidneys and liver;
• With heart failure;
• Against the background of myasthenia gravis;
• Premature babies (due to the risk of developing sleep apnea);
• Newborn babies under 6 months old.

How to use Dormicum

Dormicum according to the instructions is a strong sedative medication that requires individual dose selection and slow administration. To achieve the desired sedative effect, appropriate for age, physical condition and clinical need, dose titration is recommended. Elderly people in serious condition and children should be approached with the selection of dosage taking into account individual risk factors.

After intravenous administration, the action of Dormicum according to the instructions develops within two minutes, the maximum effect is observed after 5-10 minutes.

Before a surgical or diagnostic procedure for conscious sedation, the drug is administered intravenously. The average adult dosage is 2-2.5 mg administered 5-10 minutes before the procedure. As a rule, no more than 5 mg of the drug is administered per day. For the elderly, a total of no more than 2-3.5 mg of Dormicum is used.

Children are administered Dormicum intravenously by slow titration until the desired effect is achieved. Children under five years of age may require larger doses of medication than adolescents.

For premedication, Dormicum must be administered intramuscularly (20-60 minutes before induction of anesthesia deep into the muscle) or intravenously. After administration, to detect symptoms of an overdose, it is imperative to monitor the patient's condition, since individual sensitivity to the drug may vary. Children 1-15 years of age usually require higher doses of Dormicum than adults.

In children, the use of Dormicum as a sedative in combined anesthesia is not recommended due to the lack of necessary data.

Side effects

Dormicum, according to reviews, even when used in therapeutic dosages, especially with prolonged sedation, can cause the formation of physical dependence. The risk of its occurrence depends on the doses used and the duration of therapy, as well as on the presence of alcohol or drug dependence. Abrupt discontinuation of long-term therapy may cause withdrawal symptoms, including seizures.

Also, the use of Dormicum, according to reviews, can lead to the development of disorders from various body systems in the form of:

• Generalized hypersensitivity reactions (including cardiovascular and skin reactions, bronchospasm), anaphylactic shock (immune system);
• Confusion of consciousness, euphoria, hallucinations (mental sphere);
• Severe cardiorespiratory adverse events - respiratory depression or cessation, development of apnea, dyspnea, laryngospasm (respiratory organs);
• Skin rash, urticaria and itching (skin and subcutaneous fat);
• Severe cardiorespiratory adverse events (cardiovascular system);
• Violations and deterioration of visual acuity, double vision, nystagmus, periodic twitching of the eyelids, pre-syncope, refractive disorders, congestion in the ears, loss of balance (sense organs);
• Erythema and pain at the injection site, thrombophlebitis, thrombosis, hypersensitivity (local and general reactions).

In some cases (especially in children and the elderly), when using Dormicum, according to reviews, paradoxical reactions are observed - agitation, hostile mood, involuntary motor activity, hyperactivity, excitation paroxysms, aggressiveness and anger. Newborns and premature babies may develop convulsions, and in the elderly, after the use of Dormicum, the likelihood of falls and fractures increases.

Disturbances from the peripheral and central nervous system most often manifest themselves as a decrease in concentration, headache, dizziness, ataxia, postoperative drowsiness, anterograde amnesia. Also, according to the instructions, Dormicum can cause retrograde amnesia, athetoid movements, anxiety, delirium and drowsiness upon exiting anesthesia, sleep disturbances, dysphonia, speech illegibility, paresthesia. In some cases, after therapy, digestive disorders are observed in the form of a sour taste in the mouth, constipation, nausea, salivation, belching, and vomiting.

Storage conditions

Dormicum is a prescription sedative drug. The shelf life of the solution is five years, provided that it is stored under the conditions recommended by the instructions (at temperatures up to 30 ° C).

Dosage form:  solution for intravenous and intramuscular administration Compound:

1 ml of solution contains:

Active substance:

midazolam - 5.00000 mg.

Excipients:

sodium chloride - 5.00000 mg,

hydrochloric acid - 0.00234 ml,

1 M sodium hydroxide solution - up to pH 3.3,

water for injection - up to 1 ml.

Description: Transparent colorless liquid. Pharmacotherapeutic group:Sleeping pills ATX:  

N.05.C.D.08 Midazolam

Pharmacodynamics:

Mechanism of action

Midazolam is a short-acting benzodiazepine belonging to the group of imidobenzodiazepines. These compounds stimulate benzodiazepine receptors in the membranes of neurons of the central nervous system (CNS), which are allosterically associated with gamma-aminobutyric acid receptors (GABAd receptors). With stimulation of benzodiazepine receptors, the sensitivity of GABA receptors to GABA (inhibitory mediator) increases. When GABAA receptors are excited, C1 channels open; Cl ions - enter the nerve cells, this leads to hyperpolarization of the cell membrane. Under the action of benzodiazepines, the frequency of opening of Cl-channels increases. Thus, benzodiazepines enhance the processes of inhibition in the central nervous system.

Pharmacological effects of benzodiazepines:

1) anxiolytic (elimination of feelings of anxiety, fear, tension);

2) sedative;

3) sleeping pills;

4) muscle relaxant;

5) anticonvulsant;

6) amnestic (in high doses, benzodiazepines cause anterograde amnesia for about 6 hours, which can be used for premedication before surgical operations).

The pharmacological action is characterized by a short duration due to the rapid degradation of midazolam. It quickly causes the onset of sleep (after 20 minutes), has little effect on the structure of sleep, and has practically no aftereffect.

Onset of action: sedative - 15 minutes (intramuscular (i / m) administration), 1.5-5 minutes (intravenous (i / v) administration); introductory general anesthesia with intravenous administration - 0.75-1.5 minutes (with premedication with narcotic drugs), 1.5-3 minutes (without premedication with narcotic drugs). The duration of the amnestic action is directly dependent on the dose. The recovery time from general anesthesia is 2 hours on average. After intramuscular or intravenous use, anterograde amnesia of short duration is observed.

Pharmacokinetics:

Absorption

When administered intramuscularly, absorption of midazolam from muscle tissue is rapid and complete. The maximum plasma concentration is reached within 30 minutes. Absolute bioavailability after intramuscular injection is more than 90%.

Distribution

The pharmacokinetic profile of midazolam is linear. With intravenous administration, the distribution is biphasic. The equilibrium volume of distribution is 0.7-1.2 l / kg. Communication with plasma proteins - 96-98%. Contacting mainly with albumin, it penetrates through histohematic barriers, incl. blood-brain and placental barriers, as well as in breast milk. Small concentrations are found in the cerebrospinal fluid.

Metabolism

Midazolam is almost completely biotransformed, excreted mainly as metabolites. Hydroxylated by the CYP3A4 isoenzyme to a-hydroxymidazolam (the main metabolite in plasma and urine). Plasma concentration of a-hydroxymidazolam reaches 12% of the starting substance. Pharmacological activity is 10% of the activity of midazolam.

breeding

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

Pharmacokinetics with intravenous drip administration: in some intensive care patients, and in some elderly patients receiving drip for prolonged sedation, the elimination half-life was increased up to six times. Specific risk factors include older age, abdominal pathology, sepsis, and reduced kidney function. In these patients, infusion of midazolam at a constant rate resulted in an increase in plasma concentrations of the drug at steady state. Therefore, the infusion rate should be reduced as soon as a satisfactory clinical effect is obtained.

Pharmacokinetics in special groups of patients

Elderly patients.

In persons older than 60 years, T 1/2 can be increased four times.

Children.

After intravenous administration to children aged 3-10 years, T 1/2 is shorter than adults (1-1.5 hours), which is explained by a more intensive metabolism of midazolam.

Newborns.

In newborns, the half-life (T 1/2) is increased and averages 6-12 hours, and the clearance of the drug is slowed down.

Overweight patients.

In overweight individuals, clearance is slowed down, T 1/2 is 8.4 hours. Patients with liver failure.

The half-life of midazolam in patients with cirrhosis of the liver may be prolonged, and clearance reduced, compared with similar indicators in healthy volunteers.

Patients with renal insufficiency.

In patients with chronic renal failure, T 1/2 is the same as in healthy volunteers.

Seriously ill patients.

In critically ill patients, the half-life (T 1/2) of midazolam is increased.

Patients with heart failure.

In patients with chronic heart failure, compared with healthy volunteers, T 1/2 increases.

Indications:

adults

Introductory anesthesia.

As a sedative component in combined anesthesia.

Children

Conscious sedation before and during diagnostic or therapeutic procedures, performed under local anesthesia or without it.

Premedication before induction anesthesia.

Prolonged sedation in intensive care.

Contraindications:

Hypersensitivity to benzodiazepines or other components of the drug.

Acute respiratory failure, acute respiratory distress syndrome.

Shock, coma, acute alcohol intoxication with depression of vital functions.

Angle-closure glaucoma.

The period of childbirth (see the section "Use during pregnancy and during breastfeeding").

Carefully:

Chronic heart failure, chronic respiratory failure, liver failure, chronic renal failure, obesity, old age, children under 6 months of age (especially newborns and premature babies), organic brain damage, alcohol and drug intoxication with depression of vital functions, Myasthenia gravis.

If you have one of the listed diseases, be sure to consult your doctor before taking the drug.

Pregnancy and lactation:

There are insufficient data to assess the safety of midazolam in pregnancy. The use of benzodiazepines is possible only in the absence of other alternative methods of treatment.

Voriconazole increases the plasma concentration and half-life of midazolam by 3 times.

macrolides

Erythromycin. Increases by 1.6-2 times the plasma concentration of intravenously administered midazolam, approximately 1.5-1.8 times increases the final half-life. Although the observed changes in pharmacodynamics were relatively small, it is recommended to adjust the dose of intravenously administered midazolam, especially when prescribing large doses.

Clarithromycin. Increases by 2.5 times the plasma concentration of intravenously administered midazolam, approximately 1.5-2 times increases the final half-life.

HIV protease inhibitors

Saquinavir and other HIV protease inhibitors. With the combined use of midazolam with lopinavir and ritonavir (booster combination), the plasma concentration of intravenously administered midazolam increases by 5.4 times, which is combined with the same increase in the terminal elimination half-life.

Saquinavir only increased the subjective sensation of the effect of midazolam, so patients taking intravenous bolus doses of midazolam can be administered. With prolonged infusion of midazolam, it is recommended to reduce the initial dose by 50%. Parenteral administration of midazolam in conjunction with HIV protease inhibitors requires compliance with the conditions of hospitalization (see).

H2-histamine receptor blockers

Cimetidine and Raitidine. increases equilibrium concentrations of midazolam in plasma by 26%, but does not affect them. The simultaneous administration of midazolam and cimetidine or ranitidine does not have a clinically significant effect on the pharmacokinetics and pharmacodynamics of midazolam. can be administered intravenously in usual doses simultaneously with cimetidine and ranitidine.

Blockers of slow calcium channels

Diltiazem. A single dose of diltiazem increases the plasma concentration of intravenous midazolam by approximately 25% and lengthens the terminal half-life by 43%.

Other medicines.

Atorvastatin. Increases the plasma concentration of intravenously administered midazolam by 1.4 times.

CYP3A4 inducers

Rifampicin. After taking rifampicin for 7 days at a dose of 600 mg per day, the concentration of midazolam in the blood plasma after intravenous administration decreases by approximately 60%. The terminal half-life is reduced by approximately 5-60%.

Herbal medicines and food

Echinacea purpurea root extract. Reduces the plasma concentration of intravenously administered midazolam by 20%. The terminal half-life is reduced by approximately 42%.

St. John's wort (perforated). Reduces the plasma concentration of intravenously administered midazolam by approximately 20-40%.

The terminal half-life is reduced by approximately 15-17%.

Other interactions

Cyclosporine. There is no pharmacokinetic and pharmacodynamic interaction between cyclosporine and midazolam; no dose adjustment of midazolam is required when co-administered with cyclosporine.

Nitrendipine does not affect the pharmacokinetics and pharmacodynamics of the drug. Both drugs can be administered simultaneously; dose adjustment of midazolam is not required.

Oral contraceptives do not affect the pharmacokinetics of intramuscularly administered midazolam; these drugs can be used simultaneously without dose adjustment of midazolam.

Valproic acid. Due to the high therapeutic concentration in the blood serum, it can displace from the connection with plasma proteins (albumin), which can lead to an increase in the clinical effect of midazolam administered under emergency sedation. Against the background of the use of valproic acid, CNS depression is enhanced.

Pharmacodynamic Interactions

The co-administration of midazolam with other sedatives and hypnotics, as well as in combination with alcohol, may lead to increased sedative and hypnotic effects.

Such an interaction is possible when taking opiates and opioids (when taken as analgesics and antitussives, substitution therapy), antipsychotics (neuroleptics), various benzodiazepines used as anxiolytics or hypnotics, barbiturates, propofol, ketamine, etomidate, also while taking midazolam with antidepressants with a sedative effect, antihistamines and centrally acting antihypertensives. reduces the minimum alveolar concentration of inhalation anesthetics. With such a joint use of drugs, adequate monitoring of vital signs is necessary. Concomitant use of midazolam and alcohol should be avoided.

Spinal anesthesia may increase the sedative effect of intravenous midazolam. In this case, it is necessary to reduce the dose of midazolam.

Also, a dose reduction of intravenously administered midazolam is necessary in cases of its simultaneous use with lidocaine or bupivacaine when they are administered intramuscularly.

Drugs that activate brain activity, improve memory, attention, such as an acetylcholinesterase inhibitor - physostigmine, can reduce the hypnotic effect of midazolam. Similarly, 250 mg of caffeine partially reduces the sedative effect of midazolam.

Ginkgo biloba leaf extract

In clinical studies with ginkgo biloba leaf extract, both inhibition and induction of cytochrome P450 isoenzymes were revealed. When ginkgo biloba leaf extract was co-administered with midazolam, the concentration of the latter changed, presumably due to the effect on the CYP3A4 isoenzyme.

Special instructions:

Midazolam should only be used by professionals trained in the methods of its administration, as well as capable of providing resuscitation assistance, the need for which may arise as a result of the development of adverse reactions. Serious adverse drug reactions have been reported with midazolam, including respiratory depression, apnea, respiratory arrest, and 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 in patients with impaired respiratory function.

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

Use of midazolam in children

The use of midazolam requires special caution in children.

In children with concomitant cardiovascular diseases, the dose should be reduced, constant monitoring of vital functions is necessary. do not use in children for induction anesthesia, as well as a sedative component in combined anesthesia.

Children require relatively higher doses of midazolam (per kilogram of body weight) than adults. The drug is injected deep intramuscularly into a large muscle 30-60 minutes before induction of anesthesia.

The half-life of midazolam may be prolonged in neonates.

Special care is needed when sedating preterm infants (born less than 36 weeks' gestation) because of the risk of apnea. Rapid administration of the drug should be avoided in this group of patients.

Premature and term newborns

Due to the increased risk of apnea, special caution is recommended when used in non-intubated premature or full-term neonates. In these cases, careful monitoring of respiratory rate and blood oxygen saturation is necessary. Rapid administration of the drug is not recommended. Due to the immaturity of metabolic functions, newborns are susceptible to respiratory depression. In children with cardiovascular diseases, in order to prevent respiratory disorders, the drug should be administered slowly.

Children under 6 months old

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

In children younger than 6 months, as well as weighing less than 15 kg, the use of a solution with a concentration above 1 mg / ml is not recommended. The drug in a higher concentration is pre-diluted to 1 mg / ml. When used in pediatric practice, it must be remembered that intramuscular injection is painful. Also, special care should be taken when prescribing midazolam to the following groups of patients:

Patients over 60 years of age;

Patients with a severe general condition or chronic diseases (for example, with chronic respiratory failure, chronic renal failure, liver or heart failure);

Patients with myasthenia gravis, due to the muscle relaxant properties of midazolam, as with other CNS depressants;

Patients with alcoholism or drug addiction (including history);

Patients with organic brain damage, hospitalized in a state of shock, coma.

addictive

There are reports of some decrease in efficacy with chronic administration of midazolam for sedation in intensive care units.

Addiction

With long-term use of midazolam (long-term sedation in intensive care units), physical dependence may develop. Its risk increases with increasing dose and duration of treatment, it is also higher in patients with a history of alcoholism and (or) drug addiction.

Syndrome "cancellation"

During long-term treatment with midazolam in the intensive care unit, the development of mental and physical dependence is possible. With the sudden cancellation of midazolam, a "withdrawal" syndrome may develop, which can manifest itself with the following symptoms: headache, muscle pain, anxiety, tension, agitation, confusion, irritability, "rebound" insomnia, mood swings, hallucinations and convulsions. In order to avoid the "withdrawal" syndrome, it is recommended to gradually reduce the dose of the drug until it is canceled.

Amnesia

Midazolam can 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 outpatients discharged immediately after surgery, prolonged amnesia can be inconvenient, therefore, after parenteral administration of midazolam, the patient should be discharged only accompanied by medical personnel or persons close to him.

Paradoxical reactions

Paradoxical reactions have been reported with midazolam: 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 introduction 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.

Change in therapeutic efficacy of midazolam

In patients using inducers or inhibitors of the CYP3A4 isoenzyme, the therapeutic efficacy of midazolam may change, so it may be necessary to adjust the dose of midazolam (see section "Interaction with other drugs").

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

Concurrent use of alcohol and/or CNS depressants Concomitant use of midazolam with alcohol or CNS depressants should be avoided. Such use may increase the clinical effects of midazolam and lead to severe sedation or clinically significant respiratory depression (see section "Interaction with other medicinal products").

Alcoholism or drug addiction

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

Extract from a medical institution

After completing the necessary procedures, the patient should be observed until the full recovery of consciousness and motor abilities, the patient should be discharged, accompanied by persons close to him.

The drug contains sodium, which may be important for patients on a low-salt diet.

During the period of treatment should not be taken, especially in the first 6 hours after taking the drug.

Influence on the ability to drive transport. cf. and fur.:Sedation, amnesia, decreased concentration, impaired muscle function have a negative impact on the ability to drive a car or work with mechanisms. You should not drive vehicles or work with machines and mechanisms until the effect of the drug has completely ceased. The resumption of such activities should occur with the permission of the attending physician. Release form / dosage:Solution for intravenous and intramuscular administration 5 mg/ml. Package:

1 ml or 3 ml in ampoules. 5 ampoules in a blister pack.

1,2 or 5 blister packs with instructions for the use of the drug, a knife or an ampoule scarifier in a pack of cardboard.

20, 50 or 100 blister packs together with an equal number of instructions for the use of the drug, knives or ampoule scarifiers in a cardboard box or in a corrugated cardboard box (for a hospital).

When packing ampoules with rings and break points, knives or ampoule scarifiers are not inserted.

Storage conditions:

In accordance with the rules for the storage of psychotropic substances included in List III of the List of Narcotic Drugs, Psychotropic Substances and Their Precursors Subject to Control in the Russian Federation.

In a place protected from light at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Best before date:

Do not use after the expiry date stated on the packaging.

Conditions for dispensing from pharmacies: On prescription Registration number: LP-003720 Date of registration: 12.07.2016 / 21.08.2017 Expiration date: 12.07.2021 Registration certificate holder:MOSCOW ENDOCRINE PLANT, FSUE Russia Manufacturer:   Information update date:   24.04.2018 Illustrated Instructions