Dormicum higher single and daily doses. Dormicum - instructions for use. Use during pregnancy

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

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 i/v 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.

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

V/m 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. Usually a total dose not exceeding 10 mg is sufficient.

I/V the initial dose of Dormicum is administered in 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 the administration of the drug to non-intubated children younger than 6 months 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 (but not more than 10 mg).

Doses for children aged 12 to 16 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 I or II, under 60 years of age) are given 0.07-0.1 mg/kg (about 5 mg).

Patients over 60 years of age, debilitated or chronic: the dose is individually reduced. If the patient is not simultaneously receiving drugs, the recommended dose of midazolam is 0.025-0.05 mg/kg, the usual dose is 2-3 mg. Patients over 70 years of age i / m administration of Dormicum should be carried out carefully, under continuous supervision, because of the possibility of too much drowsiness.

Children from 1 to 15 years old: 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 IV induction drugs, 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. It is administered intravenously for 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 dose. 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 the recovery of consciousness after such doses may be delayed.

Patients over 60 who have not received premedication smaller induction doses of Dormicum are required; 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

Maintenance of the desired level of unconsciousness can be achieved either by further fractional administration of small doses (0.03-0.1 mg/kg), or by continuous IV infusion at a dose of 0.03-0.1 mg/kg h, 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 smaller doses are required to maintain anesthesia.

Children receiving ketamine for the purpose of anesthesia (ataralgesia) it is recommended to administer a dose of 0.15 to 0.20 mg/kg IM. 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

I/V the 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 value of the / in the loading dose can vary between 0.03-0.3 mg / kg, and usually a total dose of not more than 15 mg is 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 may be 0.03-0.2 mg/(kg×h). 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 is impossible to administer intravenously quickly). After that, they switch to continuous IV infusion at a dose of 0.06-0.12 mg/kg (1-2 µg/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.

newborn (<32 нед) Dormicum should be given as a continuous IV infusion at an initial dose of 0.03 mg/kg×h (0.5 µg/kg/min) and in newborns (>32 weeks) at a dose of 0.06 mg/kg/h (1 µg/kg/min). In / in the loading dose of the newborn is not administered, instead, in the first few hours, the infusion is carried out somewhat faster 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.

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 Hartman's solution in the 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.

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.

F.HOFFMANN-La ROCHE LTD ROCHE Seneksi S.a.S. / F. Hoffmann-La Roche Ltd

Country of origin

France France/Switzerland Switzerland

Hypnotic and sedative drug for premedication and induction of anesthesia

Release forms

3 ml - colorless glass ampoules (5) - packs of cardboard. 3 ml - colorless glass ampoules (10) - packs of cardboard. 3 ml - colorless glass ampoules (25) - packs of cardboard.

Description of the dosage form

Solution for intravenous and intramuscular administration in the form of a clear, colorless or slightly yellowish liquid

pharmachologic effect

Short acting benzodiazepine. The active substance of the drug 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. 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. Mechanism of action Midazolam stimulates GABA ionotropic receptors located in the central nervous system. In the presence of GABA, midazolam binds to benzodiazepine receptors on chloride ion channels, which leads to activation of the GABA receptor and a decrease in the excitability of the subcortical brain structures. As a result, midazolam has a sedative and hypnotic effect, as well as anxiolytic, anticonvulsant and central muscle relaxant effects. Several subtypes of GABA receptors have been described. Sedation, anterograde amnesia, and anticonvulsant activity are mediated through the GABAA receptor, mainly containing the ?1 subunit, anxiolytic and muscle relaxant activity is associated with an effect on the GABAA receptor, mainly containing the ?2 subunit. Midazolam has a very rapid sedative and pronounced hypnotic effect. 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 i / m administration Midazolam is absorbed from muscle tissue quickly and completely. Cmax in plasma is achieved 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. Vd in the equilibrium state is 0.7-1.2 l / kg of body weight. The degree of binding to plasma proteins, mainly albumin, is 96-98%. 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. Midazolam is hydroxylated by the 3A4 isoenzyme of the cytochrome P450 system. The main metabolite in plasma and urine is a-hydroxymidazolam. The concentration of a-hydroxymidazolam in plasma is 12% of the concentration of midazolam. a-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. Withdrawal In healthy volunteers, T1 / 2 is 1.5-2.5 hours. Plasma clearance is 300-500 ml / min. Excretion of midazolam from the body occurs mainly by the kidneys: 60-80% of the dose received is excreted in the urine as a-hydroxymidazolam glucuronide. Less than 1% of the dose taken is found in the urine as unchanged drug. T1 / 2 metabolite is less than 1 hour. With intravenous drip administration of midazolam, 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, T1 / 2 may increase by 4 times. In children from 3 to 10 years, T1 / 2 after intravenous administration is shorter than in adults (1-1.5 hours), which corresponds to an increased metabolic clearance of the drug. In newborns - perhaps due to the immaturity of the liver - T1 / 2 is increased and averages 6-12 hours, and the clearance of the drug is slowed down. In obese people, T1 / 2 is greater (8.4 h) than in people with normal body weight, probably due to an increase in Vd, adjusted for total body weight, by about 50%. The clearance of the drug is not significantly changed. T1 / 2 of the drug in patients with cirrhosis of the liver may be lengthened, and clearance may decrease, compared with similar indicators in healthy volunteers. T1 / 2 of the drug in patients with chronic renal failure is similar to that in healthy volunteers. In patients who are in extremely serious condition, T1 / 2 midazolam increases. In chronic heart failure T1 / 2 midazolam is also higher than in healthy individuals.

Special conditions

Parenteral midazolam should only be used in the presence of resuscitation equipment, since its intravenous administration can inhibit myocardial contractility and cause respiratory arrest. In rare cases, severe cardiorespiratory adverse events have developed. They consisted of depression, respiratory arrest and / or cardiac arrest. The likelihood of such life-threatening reactions increases with too rapid administration of the drug or with the introduction of a large dose (see section "Side Effects"). When performing conscious sedation by a non-anaesthetist, current best practices should be followed. When using the drug Dormicum in a hospital for one day, the patient can be discharged only after an examination by an anesthetist. The patient can leave the clinic only if there is an accompanying person. When conducting premedication after the administration of midazolam, careful monitoring of the patient's condition is mandatory, since individual sensitivity to the drug may vary and overdose symptoms may develop. Particular care is needed when parenteral administration of midazolam to patients with a high degree of risk: over 60 years of age, in an extremely serious condition, suffering from impaired respiratory function, kidney function, liver function, and cardiac dysfunction. These patients require smaller doses (see section "Method of application and doses") and constant monitoring for the purpose of early detection of violations of vital functions. With prolonged use of the drug Dormicum for sedation in the intensive care unit, a slight decrease in the effect of the drug has been described. Since the abrupt withdrawal of Dormicum, especially after prolonged intravenous use (more than 2-3 days), may be accompanied by withdrawal symptoms, it is recommended to reduce its dose gradually. The following withdrawal symptoms may develop: headache, muscle pain, increased anxiety, tension, agitation, confusion, irritability, "rebound" insomnia, mood swings, hallucinations, convulsions. Dormicum causes anterograde amnesia. Prolonged amnesia can be a problem for patients about to be discharged after a surgical or diagnostic procedure. 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, and paroxysms of arousal. Similar reactions can develop in cases of administration of sufficiently large doses of midazolam, as well as with the rapid administration of the drug. Some increased susceptibility to such reactions has been described in children and elderly patients with intravenous administration of high doses of midazolam. Simultaneous administration of midazolam with drugs inhibitors / inducers of the CYP3A4 isoenzyme may lead to a change in its metabolism, as a result of which it may be necessary

Compound

midazolam 5 mg/ml Excipients: sodium chloride, hydrochloric acid, sodium hydroxide, water for injections.

Dormicum indications for use

For adults - conscious sedation before and during diagnostic or therapeutic procedures performed under local anesthesia or without it; - premedication before induction anesthesia; - induction anesthesia; - as a sedative component in combined anesthesia; - prolonged sedation in intensive care. Children - sedation with the preservation of consciousness before diagnostic or therapeutic procedures performed under local anesthesia or without it, as well as during their implementation; - premedication before induction anesthesia; - prolonged sedation in intensive care.

Dormicum contraindications

- hypersensitivity to benzodiazepines or to any component of the drug; - acute respiratory failure, acute pulmonary insufficiency; - shock, coma, acute alcohol intoxication with depression of vital functions; - angle-closure glaucoma; - COPD (severe); - the period of childbirth. With caution: age over 60 years, extremely serious condition, respiratory failure, impaired renal and hepatic function, heart failure, premature babies (due to the risk of apnea), newborns under 6 months old, miastenia gravis.

Dormicum side effects

From the immune system: generalized hypersensitivity reactions (skin, cardiovascular reactions, bronchospasm), anaphylactic shock. From the mental sphere: confusion, euphoria, hallucinations. 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. The use of the drug Dormicum, even in therapeutic doses, especially with prolonged sedation, can lead to the formation of physical dependence. The risk of addiction increases with an increase in the dose of the drug and the duration of its use, as well as in patients suffering from alcoholism and / or having a history of drug dependence. Withdrawal of the drug, especially abruptly after prolonged intravenous use, may be accompanied by withdrawal symptoms, including convulsions. From the side of the central and peripheral nervous system: prolonged sedation, decreased concentration, headache, dizziness, ataxia, postoperative drowsiness, anterograde amnesia, the duration of which directly depends on the dose. Anterograde amnesia may occur at the end of the procedure, in some cases it lasts longer. Retrograde amnesia, anxiety, drowsiness and delirium upon recovery from anesthesia, athetoid movements

drug interaction

Pharmacokinetic interactions Metabolism of midazolam is mediated almost exclusively by the cytochrome P4503A4 system (CYP3A4 isoform). Substances, inhibitors and inducers of the CYP3A4 isoenzyme, have the potential to increase and decrease the plasma concentration, and hence the pharmacodynamic effects of midazolam. In addition to the effect on the activity of the CYP3A4 isoenzyme, no other mechanism has been found that causes clinically significant changes as a result of interdrug interactions of midazolam with other substances. However, there is a theoretical possibility of displacing the drug from its association with plasma proteins (albumin) while using it with drugs with sufficiently high therapeutic concentrations in blood plasma. For example, such a mechanism of drug-drug interaction is proposed for midazolam and valproic acid. No cases of the influence of midazolam on the pharmacokinetics of other drugs have been identified.

Storage conditions

keep away from children

Information provided

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.

Latin name: Dormicum
ATX code: N05C D08
Active substance: midazolam
Manufacturer: Cenexi (France)
Vacation from the pharmacy: On prescription
Storage conditions: at t-re up to 30°C
Best before date: 5 l.

Dormicum is an injectable solution with a hypnotic and sedative effect.

Indicated for use with:

Premedication before surgery or diagnostic measures
Introduction to general anesthesia with or without consciousness
Providing prolonged sedation in complex anesthesia or prolonged sedation in intensive care
In pediatrics: administration and maintenance of general anesthesia
Short-term treatment of insomnia.

The composition of the drug

Active - 5 or 15 mg of midazolam
Inactive - sodium chloride, hydrochloric acid, sodium hydroxide, water for injections.

Drugs in the form of an injection solution for parenteral use (in / in, in / m). The liquid is translucent, uncolored or slightly creamy. The 1% medication is placed in ampoules of 1 ml, folded into packs or contour packs of 5 or 10 pieces. LS 5 mg is packaged in ampoules of 3 ml, enclosed in packs of 5 or 10 pieces. In the box - 1 or 2 sets of ampoules, description of Dormicum.

Medicinal properties

The active ingredient in midazolam is a short-acting benzodiazepine. The substance has a very fast action due to the high metabolic rate with a short duration of effect. Differs in low toxicity.

Midazolam activates GABA nerve endings in the CNS and binds to benzodiazepine-sensitive receptors. Due to their activation, the degree of excitability of the subcortical structures of the GM decreases. As a result, hypnotic and sedative effects are achieved. In addition, the substance has anticonvulsant, antiphobic and muscle relaxant central actions.

After parenteral administration, the patient may develop short-term anterograde-type amnesia (forgetting events after starting the medication).

Pharmacokinetics

The substance is absorbed from muscle tissues in full (more than 90%) and at a high rate. Peak concentrations are formed half an hour after administration.

Distributed in the body in stages. Almost completely associated with plasma proteins (mostly with albumin). Penetrates slowly and in small quantities into the spinal cord, through the placenta into the body of the fetus, women's milk.

Biotransformation of midazolam occurs with the participation of cytochrome P450 with the formation of a metabolite with low activity (approximately 10%).

It is excreted from the body in the form of metabolites through the kidneys. The half-life depends on the state of the organ, the method of administration (in / in or / m), age and comorbidities of the patient.

Mode of application

Price: 3 ml (5 amp.) - from 800 rubles.

The medication is distinguished by a strong sedative effect, therefore, in order to avoid undesirable effects after incorrect administration, negative reactions of the body are possible. To prevent this from happening, Dormicum, according to the instructions for use, must be administered at a low speed. The dosage and duration of injection therapy is determined by the attending doctor. During the treatment course, it is recommended to constantly titrate the dosage according to the patient's condition and the response of his body to the therapy.

Particular care in the selection of the dose of Dormicum should be carried out in patients at risk (the elderly, the elderly, children, debilitated or seriously ill people with dysfunction of the heart and respiratory organs).

The effect of Dormicum will dry very quickly - within 2 minutes. after injection, reaching its peak after 5-10 minutes.

Conscious patient sedation

adults

Preparation of the patient before surgery or diagnostic procedures is carried out by intravenous infusion of drugs at a slow speed. It is strictly forbidden to enter too quickly or pour in a jet. The development of sedation in all patients proceeds differently in accordance with the rate of administration and the magnitude of the applied dosage.

Manufacturers recommend administering to adults at a rate of about 1 mg over 30 seconds. At the beginning of the course, the recommended dose is from 2 to 2.5 mg, which should be administered 5-10 minutes before. before the scheduled procedure. If the medicine did not work enough, then it is allowed to repeat the injection. In this case, the total amount of Dormicum should vary from 3.5 to 7.5 mg.

For elderly, malnourished or seriously ill patients, a reduced dosage is used at the beginning of the course - from 1⁄2 to 1 mg. In this category of patients, the drug usually begins to act much later, so if you need to make a second injection, then the drug must be administered with extreme caution, after a longer period of time. The total amount of administered drugs should be about 3.5 mg.

Children

Intravenous infusion of Dormicum should be carried out with gradual titration until the onset of sedation. It is recommended to administer drugs for 2-3 minutes. After that, you need to wait up to 5 minutes to evaluate the effect of the medication and only then decide whether or not to repeat the injection. If it is necessary to repeat the procedure, then an additional amount is also administered with constant titration until the desired result is achieved.

The recommended dosage for babies aged six months to 5 years is from 0.05 to 0.1 mg per 1 kg of body weight. the maximum allowable amount is not more than 6 mg. In case of excess, persistent sedation and the threat of insufficient ventilation of the lungs (shallow and weak breathing) are possible.
Children 6-12 years old: at the beginning - the introduction of 0.025 to 0.05 mg per 1 kg, if necessary, the administration of drugs is repeated, while the total amount of Dormicum is allowed to be increased to 0.4 mg per 1 kg. The highest allowable dosage is 10 mg.
Adolescents 13-16 years old: Adult dosage applies.

anesthesia

The use of Dormicum for premedication is indicated to achieve drowsiness and neutralize emotional overstrain with the simultaneous provocation of preoperative memory loss. The drug is approved for use in conjunction with anticholinergic drugs.

Preoperative sedation, achievement of forgetting what happened before the operation: the recommended dosage of the drug is intravenously from 1 to 2 mg, if necessary, the introduction is repeated. If the drug is used in / m, then the dosage is calculated according to the ratio of 0.07-0.1 mg per 1 kg of weight.

For adult patients (over 60 years of age, seriously ill, at risk), the dosage is set with extreme caution. At the beginning of therapy, 1⁄2 mg is administered, if necessary, repeat the dosage by slow titration after 2-3 minutes. after the first injection.

The dosage of the drug should be reduced if the drug is used simultaneously with narcotic painkillers.

Anesthesia induction

Dormicum for anesthesia is used before the introduction of other anesthetics in an individual dosage. During the procedure, it must be titrated until the desired result is obtained in accordance with the patient's condition and the body's response. If the drug is used simultaneously with other (inhalation, intravenous) drugs, then the dosage of each of them should be reduced.

Target sedation is achieved by stepwise dosage titration. The first introduction is carried out slowly in / in parts. Each subsequent introduction is carried out for 20-30 seconds at 2-minute intervals.

adults

Up to 60 years: the dosage can be up to 0.3-0.35 mg per 1 kg of body weight.
Over 60 years old, seriously ill patients, patients at risk: use a reduced amount - about 1.5-2 mg per 1 kg.
Children: it is undesirable to administer the drug, as there is not enough experience of use.

During pregnancy and breastfeeding

While there is not enough convincing information about the safety of the drug for use during pregnancy, therefore, the drug is highly undesirable to use during this period. The only exceptions are cases when Dormicum cannot be replaced by another medication, and its use is vital.

It is known that the use of the drug in high doses in the early stages of gestation or use in the last stages of pregnancy can contribute to cardiac arrhythmias in the fetus, in the newborn - the development of hypotension, impaired sucking reflex, and increased body temperature. In addition, children whose mothers were treated with benzodiazepines in the last stages of pregnancy may be born with dependence on the drug, which will manifest itself after the birth of the baby with a withdrawal syndrome.

Nursing women should be aware that the active substance is able to pass into breast milk. Therefore, after the use of Dormicum, lactation should be abandoned for 1-2 days.

Contraindications and precautions

Individual hypersensitivity to the contained components
Acute forms of respiratory and / or pulmonary insufficiency
Coma, shock
Acute form of alcohol poisoning with concomitant inhibition of life-supporting functions
Angle-closure glaucoma
Severe COPD
Pregnancy, childbirth, lactation.

Relative contraindications (appointment is possible with caution):

Old age (60+)
Extremely difficult patient condition
Heart failure, respiratory failure
Liver and/or kidney dysfunction
Prematurity (there is a high chance of sleep apnea)
Age less than 6 months
Myasthenia gravis.

Directions for use

Dormicum should not be prescribed for the primary treatment of insomnia in patients suffering from psychosis or severe depression.

It is forbidden to take ethyl alcohol during therapy. It is especially dangerous to drink alcohol or take drugs with ethanol in the first 6 hours after the administration of Dormicum.

You should refrain from driving transport or complex mechanisms, any activities with a high risk to health and life.

Cross-drug interactions

Metabolic transformation of midazolam occurs with the participation of cytochrome P4503A4. The components of this system affect the concentration of the substance, and hence the intensity of the effect. It is believed that no other mechanisms that could affect the mutual reactions of midazolam with other medicinal compounds exist. But there is an assumption that the substance is able to be displaced from plasma proteins by other substances of the drug, if they are present in high concentrations. An example of this is the interaction of a component with valproic acid.

Therefore, caution should be exercised when administering Dormicum to patients taking medications that induce or inhibit P4503A4. Otherwise, the effect of the anesthetic will be distorted, which will cause undesirable reactions of the body.

Possible effects when interacting with inhibitors of the isoenzyme CYP3A4

Ketocanazole, when used together with Dormicum (with intravenous administration), increases its plasma content by five times and increases the half-life by 3 times. Therefore, combined therapy of midazolam with ketoconazole is allowed only in a hospital clinic or other institution where there is equipment to eliminate possible respiratory complications and prolonged sedation. In addition, a detailed determination of the dosage and the phased administration of Dormicum are required, observing the interval between infusions.

The same effect is observed with the simultaneous use of other inhibitors (Fluconazole, Iraconazole, Posaconazal, Erythromycin, Clarithromycin): drugs increase the concentration of the anesthetic by 1.5-3 times and prolong the elimination period. Other drugs that can increase the content of Dormicum: HIV protease inhibitors, Cimetidine, Diltiazem.

With the simultaneous use of Dormicum with other hypnotics, sedatives and alcohol-containing drugs, the inhibitory effect on the central nervous system is enhanced. The same effect is expected when the drug is combined with barbiturates, opiates or opioids, antipsychotics, other benzodiazepines, antidepressants with sedative properties, antihistamines and central antihypertensive drugs. If possible, such combinations should be avoided, and if they cannot be canceled, then therapy should be accompanied by detailed monitoring of the functions of the respiratory system and cardiovascular system.

Spinal anesthesia is able to potentiate the sedative effect of Dormicum after its intravenous administration. To avoid unwanted reactions, the dosage of the last medication should be reduced. The same should be done when combined with lidocaine, bupivacaine.

Medications that stimulate the functions of GM, improve cognitive functions, can weaken the hypnotic effect of Dormicum.

When using Dormicum, it must be taken into account that it cannot be mixed with certain intravenous agents (6% dextran in dextrose). When combined with alkaline preparations, a precipitate forms.

Side effects

The use of Dormicum can cause a negative reaction of the body. side effects are manifested in the form of various disorders from many internal systems:

Immune system: generalized manifestations of hypersensitivity (skin rash, CVS disorders, bronchospasm), Quincke's edema, anaphylactic shock.
Mind: confusion, hallucinations, manifestations of euphoria. Paradoxical reactions (including convulsions, muscle tremors), increased activity, marked anxiety, aggression, anger, nervous excitement (especially evident in children, elderly patients) may also develop.
In some patients, the use of Dormicum, even at therapeutic dosages, can form a physical dependence on the active substance. The threat of pathology increases as the dosages increase, the duration of the course increases, the patient has other forms of dependence (on alcohol or drugs) at the time of prescribing the drug (or in history). Cancellation of Dormicum, especially sudden, is perceived by the body as a shock and causes a withdrawal syndrome, including convulsions.

CNS and PNS: prolonged state of sedation, impaired alertness, absent-mindedness, headache, dizziness, impaired motor coordination of muscles, postoperative drowsiness, dose-dependent anterograde amnesia (memory loss may occur after the procedure is completed, in some patients it is prolonged), retrograde memory loss, delirium during recovery from anesthesia, sleep disturbances, slurred speech, loss of sensation. In children (more often in premature babies), whose mothers used Dormikum, convulsions are possible after birth.
CCC: in some patients, cardiorespiratory complications (decrease in blood pressure, bradycardia, cardiac arrest, vasodilation) are possible. The likelihood of such side effects is especially high in elderly patients, as well as in patients suffering from respiratory and cardiac dysfunctions; at too high a rate of administration of the drug or after the use of strong dosages. It is also possible the occurrence of ventricular extrasystole, vasovagal crisis (hyperactivity of the vagus nerve).
Respiratory system: respiratory depression followed by cessation, apnea, shortness of breath, laryngospasm. Patients over 60 years of age and people with existing dysfunctions of the respiratory system are especially susceptible to pathology. Side effects occur when high doses of Dormicum are used or the injection is given too quickly. Also, in patients, the drug can provoke hiccups, bronchospasm, shallow breathing, tachypnea.
Gastrointestinal: nausea, bouts of vomiting, dry mouth, sour aftertaste, increased salivation, constipation, belching.
Skin and s / c fiber: rash, itching, urticaria.
Reactions at the injection site: erythema, pain at the injection site, thrombophlebitis, manifestations of hypersensitivity.
Organs of vision and hearing: decreased vigilance, double vision, arbitrary twitching of the eyelids and / or eyes, miosis, fainting, stuffy ears. In addition, the patient may lose balance, which increases the risk of injury, falls, and fractures. At risk are patients taking sedative medications, elderly and senile people.

Overdose

Benzodiazepines mainly provoke drowsiness, disorders of the speech apparatus, nystagmus, ataxia. The use of high doses of Dormicum alone generally does not pose a threat to vital functions, but can cause the development of areflexia, shortness of breath, lower blood pressure, depression of the cardiorespiratory system, and in some patients, cause the development of a coma. If the patient falls into a coma, then its duration is usually several hours. But in some patients (especially the elderly), the pathological condition may become recurrent. The overwhelming effect of Dormicum on the respiratory system is more pronounced in people with respiratory diseases.

Benzodiazepines potentiate the effects of drugs that depress the central nervous system, including ethyl alcohol.

Treatment

When carrying out measures to eliminate an overdose, it is necessary to simultaneously monitor the state of life-supporting functions. If necessary, supportive treatment is used to stabilize them. For example, it may be necessary to provide SS and respiratory functions, the CNS.

With the oppression of the central NS in severe form, Flumazenil, which is a benzodiazepine antagonist, is used. The introduction of an antidote should be carried out with appropriate monitoring of the patient's condition after the use of this medication, as well as after stopping its action. High precautions are required if the drug is to be used with drugs that lower the threshold for seizures (such as TCAs).

Analogues

Grindeks (Latvia)

Price:(10 tablets) - 112 rubles, (20 pcs.) - 189 rubles.

Drugs with zopiclone for the treatment of sleep disorders: difficulty falling asleep, temporary, situational or frequent insomnia. Produced in tablets under the shell with an active substance content of 7.5 mg.

Can only be used by adults.

Pros:

Good quality
Helps with insomnia.

Flaws:

May have the opposite effect.