Composition, form of production and packaging
A solution for intravenous and / or injections in the form of a transparent, colorless or slightly yellowish liquid.
1 ml
midazolam 5 mg
Auxiliary substances: sodium chloride, hydrochloric acid, sodium hydroxide, water d / u.
1 ml - ampoules of colorless glass (5) - packs cardboard.
1 ml - ampoules of colorless glass (10) - packs cardboard.
1 ml - ampoules of colorless glass (5) - packings of cellular contour (5) - cardboard boxes.
A solution for intravenous and / or injections in the form of a transparent, colorless or slightly yellowish liquid.
1 ml of 1 amp.
midazolam 5 mg 15 mg
Auxiliary substances: sodium chloride, hydrochloric acid, sodium hydroxide, water d / u.
3 ml - ampoules of colorless glass (5) - packs cardboard.
3 ml - ampoules of colorless glass (10) - packs cardboard.
3 ml - ampoules of colorless glass (25) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Benzodiazepine short-acting. The active substance of the drug Dormikum - midazolam - belongs to the group imidobenzodiazepines. The free base is a lipophilic substance that is poorly soluble in water.
The presence of the main nitrogen atom in position 2 of the imidobenzodiazepine ring allows midazolam to form water-soluble salts with acids. 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 range.
Mechanism of action
Midazolam stimulates ionotropic GABA A receptors located in the central nervous system. In the presence of GABA, midazolam binds to the benzodiazepine receptors on the channels for chloride ions, which leads to activation of the GABA receptor and a decrease in the excitability of the subcortical structures of the brain.As a result, midazolam has a sedative and hypnotic effect, as well as anxiolytic, anticonvulsant and central muscle relaxant action. Several subtypes of GABA Areceptors have been described. Sedation, anterograde amnesia and anticonvulsant activity are mediated through the GABA A receptor, mainly containing? 1 subunit, anxiolytic and miorelaksiruyuschaya activity associated with the effect on GABA A receptor, mainly containing? 2 subunit.
Midazolam has a very rapid sedative and pronounced sleeping pills.
After parenteral administration, there is a short anterograde amnesia (the patient does not remember the events that occurred during the most intensive action of the active substance).
PHARMACOKINETICS
Suction after the / m introduction
Midazolam is absorbed from the muscle tissue quickly and completely. C max in plasma is achieved within 30 min. Absolute bioavailability after intramuscular injection exceeds 90%.
Distribution
After intravenous administration, the midazolam concentration curve in plasma is characterized by one or two clearly expressed distribution phases. V d in the equilibrium state is 0.7-1.2 l / kg body weight. The degree of binding to plasma proteins, mainly with albumin, is 96-98%. In the cerebrospinal fluid midazolam passes slowly and in small amounts. Midazolam slowly passes through the placental barrier and enters the fetal bloodstream; small amounts are found in breast milk.
Metabolism
Midazolam is excreted almost exclusively by biotransformation. Midazolam is hydroxylated with the 3A4 isoenzyme of the cytochrome P450 system. The main metabolite in plasma and urine is a-hydroxymidazolam. The concentration of a-hydroxyimidazole in plasma is 12% of the concentration of midazolam. a-Hydroximidazolum has pharmacological activity, but only to a minimal extent (about 10%) causes the effects of intravenously administered midazolam. Data on the role of genetic polymorphism in the oxidative metabolism of midazolam are absent.
Excretion
In healthy volunteers, T 1/2 is 1.5-2.5 hours. The plasma clearance is 300-500 ml / min. Removal of midazolam from the body occurs mainly by the kidneys: 60-80% of the received dose is excreted in the urine in the form of glucuronide a-hydroximidazolam. In the form of unchanged drug in urine, less than 1% of the dose is detected. T 1/2 metabolite is less than 1 hour. With IV injection of midazolam, the kinetics of its excretion does not differ from that after the jet infusion.
Pharmacokinetics in special patient groups
In patients older than 60 years, T 1/2 may increase by 4 times.
In children from 3 to 10 years, T 1/2 after intravenous administration is shorter than in adults (1-1.5 h), which corresponds to an increased metabolic clearance of the drug.
In newborns - perhaps due to the immaturity of the liver - T 1/2 is increased and is, on average, 6-12 hours, and the clearance of the drug is slowed.
In humans, obesity T 1/2 is greater (8.4 h) than in people with normal body weight, probably due to an increase in V d , corrected for body weight, by approximately 50%. The clearance of the drug is not significantly changed.
T 1/2 of the drug in patients with cirrhosis of the liver may be prolonged, and the clearance - decrease, compared with similar indicators in healthy volunteers.
T 1/2 of the drug in patients with chronic renal failure is similar to that in healthy volunteers. In patients in extremely serious condition, T 1/2 midazolam increases.
In chronic heart failure, T 1/2 midazolam is also greater than in healthy individuals.
INDICATIONS
Adults
- sedation with preservation of consciousness before diagnostic or medical procedures, performed under local anesthesia or without it, and also during their carrying out;
- Premedication before introductory anesthesia;
- an introductory anesthesia;
- as a sedative for combined anesthesia;
- prolonged sedation in intensive care.
Children
- sedation with preservation of consciousness before diagnostic or medical procedures, performed under local anesthesia or without it, and also during their carrying out;
- Premedication before introductory anesthesia;
- prolonged sedation in intensive care.
DOSING MODE
Midazolam - a strong sedative, requiring slow administration and individual selection of a dose.
The dose should be selected individually, and titration of the dose is strongly recommended to safely achieve the desired sedative effect, which corresponds to the clinical need, the physical condition and age of the patient, and the medication he receives.
In patients older than 60 years, patients in extremely serious condition, as well as with a high degree of risk and in patients of childhood, the dose should be chosen carefully, taking into account individual risk factors.
The drug begins approximately 2 minutes after intravenous administration. The maximum effect is achieved within 5-10 minutes.
Sedation with Consciousness
For sedation with preservation of consciousness before a diagnostic or surgical procedure, the drug Dormikum enter in / in. The dose should be selected individually, carry out its titration; the drug can not be injected quickly or in jet. The onset of sedation varies individually, depending on the patient's condition and dosing regimen (rate of administration, dose size). If necessary, repeated administration is possible.
Dormicum for the purpose of conscious sedation should be used with caution in patients with impaired respiratory function (see section "Special instructions").
Adult Dormicum should be administered iv slowly, at a rate of approximately 1 mg per 30 seconds.
For patients <60 years of age, the initial dose is 2-2.5 mg, administered 5-10 minutes before the procedure. If necessary, repeated administration in a dose of 1 mg.The average total dose is in the range 3.5-7.5 mg. Usually there is enough of a total dose not exceeding 5 mg.
Patients aged ≥60 years; patients who are in extremely serious condition, and also with a high degree of risk, the initial dose is reduced to 0.5-1 mg and injected it 5-10 minutes before the procedure. If necessary, re-administered in a dose of 0.5-1 mg. Since in these patients the maximum effect can not be achieved so quickly, additional doses should be titrated slowly and cautiously. Usually there is enough of a total dose not exceeding 3.5 mg.
Children in / in the introduction of the drug Dormikum conducted slow titration until the effect. The initial dose of Dormikum is given within 2-3 minutes. Then, before proceeding with the procedure or introducing a second dose, it is recommended to wait another 2-5 minutes to assess the sedation effect. If sedation needs to be strengthened, the dose continues to be titrated with small "steps" until the necessary degree of sedation is reached. Infants and children younger than 5 years of age may require significantly higher doses than older children and adolescents.
Children younger than 6 months are particularly prone to airway obstruction and hypoventilation, so the use of Dormikum with a view to sedation with preservation of consciousness in children under 6 months is not recommended, except when the possible benefits exceed potential risks. In these cases, it is extremely important to titrate the dose in small "steps" to achieve a clinical effect, and also carefully monitor patients. The initial dose should be minimally possible with the available technical characteristics of the equipment used
For children aged 6 months to 5 years, the initial dose is 0.05-0.1 mg / kg. To achieve the desired effect, the total dose can be increased to 0.6 mg / kg, but it should not exceed 6 mg. With the introduction of higher doses, it is possible to develop prolonged sedation and the risk of hypoventilation (see section "Special instructions").
For children aged 6 to 12 years, the initial dose is 0.025-0.05 mg / kg, the total dose can be increased to 0.4 mg / kg, but it should not exceed 10 mg. With the introduction of higher doses, it is possible to develop prolonged sedation and the risk of hypoventilation (see section "Special instructions").
Doses for children from 13 to 16 years old are the same as for adults.
In / m administration (for children from 1 year to 16 years of age) the recommended dose of 0.05-0.15 mg / kg, is administered 5-10 minutes before the procedure.Usually there is enough of a total dose not exceeding 10 mg.
At a body weight of less than 15 kg, the administration of solutions of midazolam with a concentration of more than 1 mg / ml is not recommended. Solutions with a higher concentration should be diluted to a concentration of 1 mg / ml.
Anesthetic
Premedication
Premedication drug Dormikum shortly before the procedure has a sedative effect (the occurrence of drowsiness, and the elimination of emotional stress), and also causes preoperative amnesia. For premedication, the drug is administered IV or IM (deep into the muscle 20-60 minutes before the anesthesia).
After the administration of Dormikum to detect symptoms of overdose, it is necessary to observe the patient, since the individual sensitivity to the drug can vary.
Dormicum can be used in combination with anticholinergics.
Adults <60 years of age and classified in Class I and II by the classification system of physical status assessment, adopted by the American Society of Anesthesiologists
For preoperative sedation and removal of memory for preoperative events, the drug is administered in a dose of 1-2 mg IV, if necessary, repeating the introduction, or IM in a dose of 0.07-0.1 mg / kg body weight.
Adults-60 years, patients in extremely serious condition, patients with a high degree of risk require reduction and individual dose selection.
The recommended initial dose for intravenous administration is 0.5 mg, if necessary, increase the dose by slow titration. Before introducing a second dose, wait 2-3 minutes to assess the effect.
The recommended dose for intravenous administration is 0.025-0.05 mg / kg (usually 2-3 mg), provided that the patient does not receive drugs at the same time.
The dose of Dormikum should be reduced with its simultaneous administration with narcotic analgesics.
Children from 1 to 15 years old relatively higher doses are required (per kg body weight) than for adults.
Doses in the range of 0.08-0.2 mg / kg with the / m administration are effective and safe. The drug must be injected deep into the large muscle 30-60 minutes before the anesthesia.
Children with body weight less than 15 kg are not recommended to administer midazolam solutions with a concentration of more than 1 mg / ml. Solutions with a higher concentration should be diluted to a concentration of 1 mg / ml.
Introductory anesthesia
If Dormikum is used for introductory anesthesia before the introduction of other anesthetics, the individual reaction of patients may be different. The dose should be titrated until the desired effect is achieved in accordance with the age and clinical condition of the patient. When Dormikum is administered before or in combination with other intravenous or inhaled preparations for anesthesia, the initial doses of each drug can be significantly reduced, sometimes up to 25% of the initial dose set.
The desired level of sedation is achieved by stepwise titration of the dose. Induction dose of Dormikum should be administered intravenously slowly, fractional. Each subsequent administration of the drug in an amount of not more than 5 mg, should be done within 20-30 seconds, making 2-minute intervals between the administrations.
For adults <60 years, a dose of 0.2 mg / kg is administered iv in 20-30 seconds, waiting for 2 minutes to evaluate the effect. Usually this dose is sufficient to achieve a satisfactory effect.
In the absence of premedication, the dose may be increased to 0.3-0.35 mg / kg body weight. It is administered intravenously for 20-30 seconds, waiting for 2 minutes to assess the effect. If necessary, to complete the induction, the drug is administered additionally in amounts equal to approximately 25% of the initial dose.Alternatively, liquid inhalation anesthetics may be used to complete the induction. In cases of immunity, the induction dose of Dormikum can reach 0.6 mg / kg, however, restoration of consciousness after such doses may be slowed down.
Adults? 60 years, patients in extremely serious condition, as well as with a high degree of risk in the absence of premedication, require the smallest induction doses of Dormikum, equal to 0.15-0.2 mg / kg. In the presence of premedication, an administration of 0.05-0.15 mg / kg is recommended for 20-30 seconds, waiting for 2 minutes to evaluate the effect. Usually this dose is enough.
Dormicum В® is not recommended for introductory anesthesia in children , since the experience of its use in this age group is limited.
As a sedative for combined anesthesia
Adults <60 years of age use Dormikum as a sedative in combined anesthesia is carried out either by fractional iv 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 per hour, usually in combination with analgesics. Doses and intervals between administrations depend on the individual reaction of the patient.
Adults-60 years old, patients in extremely serious condition, as well as a high risk for maintenance of anesthesia, require smaller doses.
The use of Dormikum В® as a sedative for combined anesthesia in children is not recommended, as the experience of its use is limited.
Long-term sedation in intensive care
The desired sedative effect is achieved by stepwise titration of the dose, followed by either continuous infusion or fractional fluid administration of the drug, depending on the clinical need, the patient's condition, age and concomitantly administered drugs.
Adults with an IV loading dose 0.03-0.3 mg / kg is administered fractional, slowly. Each repeated dose of 1-2.5 mg is administered for 20-30 seconds, observing the 2-minute intervals between the administrations.
Patients with hypovolemia, vasoconstriction or hypothermia exercise dose are reduced or not administered at all.
If Dormikum is used simultaneously with strong analgesics (in particular, morphine, methadone, pethidine, fentanyl, alfentanil, buprenorphine, pentazocine and derivatives of each subgroup), the latter should be administered before it so that the dose of Dormikum can be safely titrated at the height of sedation , caused by an analgesic.
IV dose maintenance dose can vary within the range of 0.03-0.2 mg / kg per hour. Patients with hypovolemia, vasoconstriction or hypothermia maintain a dose that is reduced. If the condition of the patient allows, the degree of sedation should be regularly assessed. In the case of prolonged sedation, the development of tolerance is possible, as a result of which the dose will need to be increased.
Preterm and premature neonates , as well as children weighing less than 15 kg, do not recommend the administration of solutions of midazolam with a concentration of more than 1 mg / ml. Solutions with a higher concentration should be diluted to a concentration of 1 mg / ml.
Children younger than 6 months of the drug should be administered by continuous intravenous infusion .
Newborns with gestational age <32 weeks Dormikum should be administered at an initial dose of 0.03 mg / kg / h (0.5 Ојg / kg / min).
Newborns with gestational age> 32 weeks and children younger than 6 months - at a dose of 0.06 mg / kg / h (1 Ојg / kg / min).
B / in a loading dose is not administered, instead for the first few hours of infusion is carried out somewhat faster to achieve therapeutic plasma concentrations. The rate of infusion must be frequently and thoroughly reviewed, especially in the first 24 hours to enter the lowest effective dose and reduce the potential for drug accumulation. It is necessary to carefully monitor the respiratory rate and oxygen saturation.
Children older than 6 monthsLocated on the ventilator, intubated and also to establish the desired clinical effect of loading dose of 0.05-0.2 mg / kg administered in / slow not less than (i.v. administered can not rapidly) for 2-3 minutes. Thereafter, switching to the continuous on / in infusion at a dose of 0.06-0.12 mg / kg / hr (1-2 ug / kg / min). If necessary, to increase or maintain the desired effect, the rate of infusion can be increased or reduced (typically 25% of the initial or subsequent speed) or dormicum administered additional doses of the drug.
If the drug infusion dormicum begin in patients with impaired hemodynamics and normal loading dose must be titrated in small "steps" by controlling the hemodynamic parameters (blood pressure lowering). These patients have a tendency to respiratory depression in the application preparation dormicum В® , therefore, careful monitoring of respiratory rate and oxygen saturation.
Special dosage
term and preterm infants, and children weighing less than 15 kg are not recommended administration of midazolam solutions with concentration higher than 1 mg / ml. Solutions with higher concentrations must be diluted to a concentration of 1 mg / ml.
Children under 6 monthsnot recommended in / with the introduction of midazolam, as they are particularly prone airway obstruction and hypoventilation, except in cases of sedation in intensive care units.
Dormicum not indicated for use in children for induction of anesthesia and as a sedative component in combined anesthesia, as there are only limited data on the data reading in children.
Patients older than 60 years of age usually require lower doses of midazolam. There should be continuous monitoring of vital signs.
In patients with impaired renal functionFree pharmacokinetics of midazolam is similar to that in healthy volunteers. However, it was shown that patients with chronic kidney disease accumulation a-gidroksimidazolama, which may lead to an increase in the duration of the clinical effects of the drug and to prolong sedation.
In patients with impaired liver function , a decrease in clearance of midazolam after / in the introduction, and hence increase the final T 1/2 , which can lead to amplification and prolongation of its clinical effects. Such patients may require lower doses of midazolam, as well as appropriate monitoring of vital signs.
Specific guidance on dosing
Dormicum solution formulation in ampoules can be diluted with 0.9% sodium chloride, 5% and 10% glucose solution (5% and 10% dextrose and levulose 5% solution), Ringer's solution, Hartmann solution and in the ratio of 15 mg midazolam in 100-1000 ml infusion solution. These solutions remain physically and chemically stable for 24 hours at room temperature and 3 days at 5 В° C.
It should not be diluted dormicum 6% dextran solution to Wed they say. weight 50000-70000 Da in dextrose. Dormicum not be mixed with alkaline solutions, as midazolam gives a precipitate of sodium bicarbonate.
The use of other solvents in addition to the above should be avoided.
From the microbiological point of view, the prepared solution should be used immediately. If the preparation is not used immediately, the time and conditions of storage of the prepared solution are the responsibility of the user and should not exceed 24 hours at a temperature of from 2 В° C to 8 В° C and only if the preparation of the solution was carried out under controlled aseptic and validiruemyh usloviyah.Ampuly dormicum drug intended for single ispolzovaniya.Neispolzovanny solution should be discarded.
Before the introduction must be viewed rastvor.Tolko clear solution free from visible foreign particles suitable for use.
After freezing may precipitate which is dissolved by shaking at room temperature.
SIDE EFFECT
Immune system: reaction generalized hypersensitivity (skin, cardiovascular reactions, bronchospasm), anaphylactic shock.
On the part of the psychic sphere: confusion, euphoria, hallucinations.
There are cases paradoxical reactions such as agitation, involuntary motor activity (including tonic-clonic convulsions and muscle tremor), hyperactivity, spirits hostility, anger, aggression, excitation paroxysms, especially among children and senile patients.
Application dormicum preparation, even at therapeutic doses, especially in prolonged sedation can lead to the formation of physical dependence. The risk of dependence increases with the dose and duration of its application, and in patients suffering from alcoholism and / or having a history of drug dependence. Removal of the drug, especially sharp after his prolonged intravenous administration, it may be accompanied by withdrawal symptoms, including convulsions.
On the part of the central and peripheral nervous system:prolonged sedation, decreased concentration, headache, dizziness, ataxia, somnolence postoperative, 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. Retrograde amnesia, anxiety, drowsiness and delirium during recovery from anesthesia, athetoid movements, sleep disorders, dysphonia, indistinct speech, paresthesia.
Premature babies and newborns seizures are described.
Cardio-vascular system:in rare cases develop severe cardiorespiratory adverse events. They were to cardiac arrest, lowering blood pressure, bradycardia, vasodilation. The probability of such life-threatening reactions is higher in adults older than 60 years and in patients with concomitant respiratory failure or heart failure, especially if the drug is administered too quickly or in large doses (see. "Special Instructions" section). Tachycardia, bigemini, premature ventricular contractions, vasovagal crisis, rhythm atrioventricular connection.
On the part of the respiratory system:in rare cases develop severe cardiorespiratory adverse events. They were to oppression, respiratory arrest, the development of apnea, dyspnea, laryngospasm. The probability of such life-threatening reactions is higher in adults older than 60 years and in patients with concomitant respiratory failure or heart failure, especially if the drug is administered too quickly or in large doses (see. "Special Instructions" section). Hiccups, bronchospasm, hyperventilation, wheezing, shortness of breath, airway obstruction, tachypnea.
On the part of the gastrointestinal tract: nausea, vomiting, constipation, dry mouth, a sour taste in the mouth, salivation, belching.
Skin and subcutaneous tissue: skin rash, urticaria, pruritus.
General and local reactions:erythema and pain at the injection site, thrombophlebitis, thrombosis, hypersensitivity.
From the senses: the violation and the deterioration of visual acuity, diplopia, nystagmus, pinpoint pupils, periodic twitching eyelids, lightheadedness, refractive error, congestion in the ears, loss of balance.
In elderly patients, after administration of benzodiazepines increases the risk of falls and fractures.
CONTRAINDICATIONS
- kbenzodiazepinam or hypersensitivity to any component of the formulation;
- acute respiratory distress, acute pulmonary insufficiency;
- shock, coma, acute alcohol intoxication with depression of vital functions;
- an angle-closure glaucoma;
- COPD (Severe);
- childbirth.
Precautions: age over 60 years, it is a serious condition, respiratory failure, impaired kidney and liver function, heart failure, premature babies (because of the risk of apnea), infants younger than 6 months, miastenia gravis.
PREGNANCY AND LACTATION
Data to assess the safety of midazolam in pregnancy is not enough.
Benzodiazepines should not be used during pregnancy unless it is not a safer alternative. Use of the drug in the last trimester of pregnancy or at high doses during the first stage of labor leads to heart rhythm abnormalities in the fetus, hypotension, a violation of sucking, hypothermia and moderate respiratory depression in the neonate. Moreover, in children whose mothers were in the late stages of pregnancy is long received benzodiazepines, can form a physical relationship with a certain risk of abstinence syndrome in the postnatal period.
Since midazolam in small quantities into breast milk, nursing mothers recommended to interrupt breastfeeding for 24 h after administration of midazolam.
APPLICATION FOR FUNCTIONS OF THE LIVER
Special care is needed when parenterally administered midazolam in patients suffering from renal dysfunction. These patients require lower dosages (see. "Dosage and Administration" section), and continuous monitoring for early detection of disorders of vital functions.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Special caution is necessary when parenterally administered midazolam to patients with impaired liver function .. These patients require lower dosages (see. "Dosage and Administration" section), and continuous monitoring for early detection of disorders of vital functions.
APPLICATION FOR CHILDREN
Perhaps the use of indications and at the recommended doses with all the precautions.
APPLICATION IN ELDERLY PATIENTS
Special caution is necessary when parenterally administered midazolam in patients older than 60 years. These patients require lower dosages (see. "Dosage and Administration" section), and continuous monitoring for early detection of disorders of vital functions.
SPECIAL INSTRUCTIONS
Midazolam for parenteral administration should be used only if the saving equipment since its on / in the introduction may depress myocardial contractility and cause respiratory arrest. In rare cases develop severe cardiorespiratory adverse events. They were to oppression, respiratory arrest and / or cardiac arrest. The probability of such life-threatening reactions increased at too rapid administration of the drug or when administered in high dose ( "Side effects" refer. Section).
In conducting conscious sedation physician anesthesiologist should not stick to the existing practical recommendations.
When using the drug dormicum in the hospital one day a patient may be discharged only after examining the anesthetist. The patient can leave the hospital only if the accompanying person.
When conducting sedation after administration of midazolam is required careful monitoring of the patient, since individual sensitivity to the drug can vary and may develop the symptoms of an overdose.
Special caution is necessary when parenterally administered midazolam in patients with high-risk: older than 60 years who are in critical condition, suffering from a violation of the respiratory function, kidney function, liver, cardiac abnormalities. These patients require lower dosages (see. "Dosage and Administration" section), and continuous monitoring for early detection of disorders of vital functions. With prolonged use, the drug dormicum for sedation in the intensive care unit described some reduction effect of the drug.
Since the abrupt withdrawal of the drug dormicum, especially after prolonged / in use (2-3 days), can be accompanied by withdrawal symptoms, it is recommended to reduce the dose gradually. The following withdrawal symptoms may develop headache, muscle aches, increased anxiety, stress, a state of excitement, confusion, irritability, "rebound" insomnia, mood swings, hallucinations, seizures.
Dormicum cause anterograde amnesia. Prolonged amnesia can be a problem for patients who are going to write after a surgical or diagnostic procedure.
There are cases paradoxical reactions such as agitation, involuntary motor activity (including tonic-clonic convulsions and muscle tremor), hyperactivity, spirits hostility, anger, aggression, excitation paroxysms. Such reactions can develop in cases of administration of fairly large doses of midazolam as well as the rapid introduction of the drug. Some increased susceptibility to similar reactions described in children and elderly patients with / in the introduction of high doses of midazolam.
Simultaneous treatment with drugs midazolam inhibitors / inducers of CYP3A4 isoenzyme may alter its metabolism, whereby it may be necessary to change the corresponding doses of midazolam (cm. 'Interaction with other drugs "section).
T 1/2the drug can be prolonged in patients with impaired liver function, low cardiac output and in neonates (see. "Dosage and Administration" section, subsection "Special dosage").
Particular caution is needed during sedation in premature infants (born at gestational age less than 36 weeks), if they are not intubated, because of the risk of apnea. It is required to avoid the rapid introduction of the drug in this patient group. Careful monitoring of respiratory rate and oxygen saturation.
Children younger than 6 months are particularly prone to airway obstruction and hypoventilation, therefore, in these cases, it is imperative to titrate the dose, increasing its smaller "steps" to achieve the clinical effect, as well as carefully monitor respiratory rate and oxygen saturation.
Sharing dormicum the drug should be avoided with alcohol and / or drugs depressing the central nervous system. In such cases may increase the clinical effects dormicum drug development marked sedation and clinically significant inhibition of the respiratory and cardiovascular activity (see. "Interaction with other medicinal products" section).
Should be avoided dormicum drug in patients suffering from alcoholism, as well as having a history of drug addiction.
As with any drug, and CNS depressant having myorelaxant action, particular care should be observed when midazolam is administered to patients with myastenia gravis.
Impact on the ability to drive vehicles and manage mechanisms
Sedation, amnesia, decreased concentration, impaired muscle function have a negative impact on the ability to drive a car or operate machinery. You should not drive vehicles or operate machinery or to complete cessation of the effect of the drug. The resumption of these activities should take place with the approval of the treating physician.
OVERDOSE
Simtpomy: benzodiazepines is often the cause of drowsiness, ataxia, dysarthria and nystagmus. Dormicum overdose of the drug in it and
