Midanium

Package leaflet: Information for the patient

MIDANIUM, 1 mg/ml, solution for injection
MIDANIUM, 5 mg/ml, solution for injection
Midazolam
Please read the entire leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any further questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

1. What Midanium is and what it is used for
2. Important information before using Midanium
3. How to use Midanium
4. Possible side effects
5. How to store Midanium
6. Contents of the pack and other information

1. What Midanium is and what it is used for

Midanium contains midazolam as the active substance. Midazolam belongs to a group of medicines called benzodiazepines. It has a short-acting, potent calming and sleep-inducing effect.

Midanium is used in adults:

• for sedation (calming, reducing anxiety and agitation) while maintaining consciousness, before and during short diagnostic and therapeutic procedures;
• for patient preparation (premedication) before various procedures, e.g. before surgery or endoscopy;
• as a sedative component prior to induction of general anaesthesia, before administration of another anaesthetic agent;
• for sedation in intensive care units.

Midanium is used in children:

• for sedation (calming, reducing anxiety and agitation) while maintaining consciousness, before and during short diagnostic and therapeutic procedures;
• for patient preparation (premedication) before various procedures, e.g. before surgery or endoscopy;
• for sedation in intensive care units.

2. Important information before using Midanium

When not to use Midanium:

• if the patient is allergic to midazolam (or other benzodiazepines) or any of the other ingredients of this medicine (listed in section 6);
• if the patient has severe respiratory insufficiency or acute respiratory depression (very serious breathing difficulties).

Warnings and precautions
Before starting treatment with Midanium, discuss this with your doctor or nurse.
Consult your doctor if the patient:

• is over 60 years old or is weakened;
• has impaired liver function, chronic liver or kidney failure;
• has chronic respiratory insufficiency;
• is in a serious condition, especially with heart disease and breathing difficulties;
• has myasthenia gravis (a chronic disease characterized by muscle weakness). Patients with any of the above conditions should inform their doctor.

After receiving Midanium, the patient should be discharged from hospital or an outpatient clinic only with the doctor's approval. A caregiver should accompany the patient after discharge.
Do not use this medicine for prolonged periods, as this may increase the risk of dependence and development of tolerance to the medicine. Tolerance means progressively reduced effectiveness of the medicine with continued use, requiring higher doses to achieve the same effect.

Children

• Midanium should be used in infants under 6 months of age only in intensive care units.
• Paradoxical reactions (symptoms listed in section 4, "Possible side effects") may occur in children during treatment with Midanium. If such symptoms occur, stop using the medicine immediately.
• Particular caution is required in children with heart disease (especially with unstable circulation).

Midanium and other medicines
Inform your doctor about all medicines currently used or recently used, as well as any medicines the patient plans to use.
Midanium and other concomitantly used medicines may interact and affect each other's actions. This is particularly true for the following medicines:

• antifungal medicines (ketoconazole, voriconazole, fluconazole, itraconazole, posaconazole);
• macrolide antibiotics (erythromycin, clarithromycin);
• HIV protease inhibitors (medicines used in HIV infection – saquinavir);
• verapamil and diltiazem (calcium channel blockers used mainly in cardiovascular diseases);
• atorvastatin (a medicine that lowers blood cholesterol);
• aprepitant (an antiemetic medicine);
• rifampicin (an antibiotic);
• phenytoin (an anticonvulsant medicine);
• efavirenz (a medicine used in HIV infection);
• strong painkillers (called opioid analgesics, e.g. morphine, buprenorphine);
• medicines used in psychiatric disorders (e.g. haloperidol, carbamazepine);
• sedatives, anxiolytics, and hypnotics;
• medicines used to treat depression (fluoxetine, fluvoxamine);
• medicines used to treat allergies (with sedative effects);
• hydralazine (a medicine for hypertension);
• inhaled anaesthetics used for general anaesthesia;
• herbal mixtures containing St. John's wort extract (Hypericum perforatum).

Concomitant use of Midanium and opioids (strong painkillers, substitution therapy drugs for addiction, and some cough medicines) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and potentially life-threatening effects. Therefore, concomitant use of these medicines should only be considered if no alternative treatment options are available.
If your doctor prescribes Midanium together with opioid medicines, the treating physician should reduce the dose and recommend the shortest possible treatment duration.
Inform your doctor about all opioid medicines you are taking and strictly follow the doctor's dosing instructions. It may be helpful to inform friends or family members about the risks so they are aware of the symptoms listed above. If such symptoms occur, contact your doctor immediately.

Midanium and alcohol
Alcohol (ethanol) significantly enhances the sedative effect of midazolam. Consumption of alcohol during treatment with Midanium is contraindicated.

Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine.
Midazolam may be used during pregnancy only if clearly necessary.
The use of midazolam during caesarean section is not recommended.
Midazolam passes into human milk in small amounts. If use of the medicine is necessary, the patient should stop breastfeeding and may resume 24 hours after administration of midazolam.

Driving and operating machinery
After administration of the medicine, the following may occur: sedation, amnesia, concentration disturbances, and impaired muscle function, which may negatively affect performance of tasks requiring heightened attention.
Do not drive or operate machinery until full recovery of function.
Your doctor will decide when the patient may resume these activities.

Midanium contains sodium
This medicine contains 3.16 mg of sodium (the main component of table salt) in each ml. This corresponds to 0.16% of the maximum recommended daily intake of sodium in the adult diet.
The medicine may be diluted – see section below, "Instructions for preparation and administration of Midanium". When calculating the total sodium content in the prepared diluted solution, include the sodium originating from the diluent. For accurate information on the sodium content in the solution used for dilution, refer to the patient leaflet of the diluent used.

3. How to use Midanium

This medicine should always be used as directed by the physician. If in doubt, consult your doctor.

• Midanium is administered by medical personnel.
• The medicine is given intramuscularly, intravenously, and rectally.
• The doctor will determine the dosage and duration of treatment individually for each patient.

Detailed dosage information is contained in the section "Information intended

exclusively for healthcare professionals."
Administration of a higher than recommended dose of Midanium
The medicine is administered by healthcare personnel, therefore it is highly unlikely that a patient will receive more medicine than should be given. After an overdose of midazolam, the following may occur: drowsiness, lack of motor coordination, speech disturbances or slurred speech, and nystagmus. In more severe cases, loss of reflexes, apnea, low blood pressure, serious breathing difficulties, and in rare cases – coma, may occur.
If a patient suspects having received a higher dose than recommended, medical advice should be sought immediately, so that appropriate treatment can be administered.

If a dose of Midanium is missed
Do not administer a double dose to make up for a missed dose.

Discontinuation of Midanium treatment
In cases of prolonged midazolam use in intensive care units, abrupt discontinuation of the medicine may lead to symptoms of so-called withdrawal syndrome. These symptoms include: headache, muscle pain, anxiety, tension, restlessness, confusion, irritability, recurring insomnia, mood changes, hallucinations, and seizures.
The physician will appropriately adjust the dose and duration of treatment to minimize the risk of these symptoms occurring.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
The following side effects may occur during treatment with this medicine. Their frequency is unknown and cannot be determined from the available data.
Discontinue use of Midanium and seek immediate medical attention if any of the following side effects occur. These may be life-threatening and may require immediate treatment:

• Anaphylactic shock (a life-threatening allergic reaction). Symptoms may include sudden rash, itching, or raised, itchy rash (urticaria), and swelling of the face, lips, tongue, or other parts of the body. The patient may also experience shortness of breath, wheezing or difficulty breathing, or pale skin, weak and rapid pulse, or feeling faint. Additionally, chest pain may occur, which could be a symptom of a serious allergic reaction known as Kounis syndrome.
• Shortness of breath and difficulty breathing (sometimes leading to respiratory arrest), apnea;
• Laryngeal muscle spasm causing choking;
• Heart disorders such as slowed heart function (bradycardia), vasodilation, cardiac arrest.

Other side effects, frequency unknown (frequency cannot be determined from available data):

• Confusion, euphoria, hallucinations;
• Agitation, feelings of hostility and rage, aggression, episodes of excitement, involuntary movements (including clonic-tonic seizures and muscle tremors), excessive activity, acts of violence (so-called paradoxical reactions, particularly reported in children and elderly patients); physical dependence and withdrawal symptoms, drug abuse, seizures (in preterm infants and newborns, also as withdrawal symptoms);
• Sedation (excessive calming) prolonged and postoperative, reduced level of consciousness, drowsiness, dizziness; lack of motor coordination (ataxia); anterograde amnesia (the patient does not remember events that occurred shortly after administration of the medicine) – the duration of these side effects depends on the dose administered;
• Hiccups;
• Vasodilation;
• Hypotension;
• Dryness of the oral mucosa, nausea, vomiting, constipation;
• Skin rash, urticaria, itching;
• Severe venous disorders (thrombophlebitis and venous thrombosis);
• Pain and redness at the injection site;
• Fatigue;
• Increased risk of falls and fractures has been reported in elderly patients and patients concurrently taking sedative medicines.

Prolonged intravenous administration of midazolam, even at therapeutic doses, may lead to physical dependence, and abrupt discontinuation of the medicine may be accompanied by withdrawal symptoms, including seizures – see section "Discontinuation of Midanium treatment".
In elderly and weakened patients, especially those with heart disease and breathing difficulties, more pronounced side effects may occur, particularly after too rapid injection of the medicine or after administration of large doses.

Reporting of side effects
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181 C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Midanium

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and ampoule. The expiry date refers to the last day of the stated month.
The label on the packaging: EXP indicates the expiry date, and Lot indicates the batch number.
Store below 25°C. Do not freeze.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Midanium contains

• The active substance is midazolam. 1 ml of solution contains 1 mg or 5 mg of midazolam, respectively.
• Other ingredients: sodium chloride, disodium edetate, hydrochloric acid 10%, sodium hydroxide 10% or hydrochloric acid 10% (for pH adjustment), water for injections.

What Midanium looks like and contents of the pack
Midanium 1 mg/ml, solution for injection is a colorless, clear liquid.
The cardboard pack contains 10 ampoules of colorless glass, each containing 5 ml.
Midanium 5 mg/ml, solution for injection is a colorless or pale yellow, clear liquid.
The cardboard pack contains 10 ampoules of colorless glass, each containing 1 ml, or 5 ampoules of colorless glass, each containing 3 ml, or 5 ampoules of colorless glass, each containing 10 ml.

Marketing authorization holder and manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. +48 22 364 61 01

Information intended exclusively for healthcare professionals

MIDANIUM, 1 mg/ml, solution for injection
MIDANIUM, 5 mg/ml, solution for injection
Midazolam
Preparation and administration instructions for Midanium

• Midanium is administered intramuscularly, intravenously, and rectally.
• Midazolam should be administered only by experienced physicians in a fully equipped facility with monitoring and life-support equipment for respiratory and cardiovascular systems, and by personnel adequately trained in recognizing and managing expected adverse reactions, including cardiopulmonary resuscitation.
• Midanium may be mixed with 500 ml of the following infusion solutions:
  • 5% glucose solution;
  • 0.9% NaCl solution;
  • 4% glucose solution with 0.18% NaCl solution.
    The prepared solution maintains physicochemical stability when stored at room temperature for 24 hours. From a microbiological standpoint, the solution should be used immediately after preparation. If not used immediately, the user is responsible for storage conditions and duration prior to use. There is no evidence that midazolam undergoes adsorption onto plastic components of infusion sets or syringes.
• Midanium 5 mg/ml may be mixed with morphine sulfate (Morphini sulfas WZF 20 mg/ml) (see also "Warnings and precautions" below) within the following active substance ratios: 10 mg morphine sulfate with midazolam in doses ranging from 1.66 mg to 10 mg.
  To prepare a mixture of 10 mg morphine sulfate : 1.66 mg midazolam, mix 2.1 ml of Morphini sulfas WZF 20 mg/ml with 1.4 ml of Midanium 5 mg/ml.
  To prepare a mixture of 10 mg morphine sulfate : 10 mg midazolam, mix 1.0 ml of Morphini sulfas WZF 20 mg/ml with 4.0 ml of Midanium 5 mg/ml.
  The shelf life of the mixture of Morphini sulfas WZF 20 mg/ml and Midanium 5 mg/ml is 24 hours. Chemical and physical stability has been demonstrated for 24 hours at 25°C. The mixture should be prepared immediately before administration. From a microbiological standpoint, the prepared mixture should be used immediately. If not used immediately, the user is responsible for storage conditions and duration. If necessary, the prepared mixture may be stored for up to 24 hours at 25°C, provided it is prepared under controlled and validated aseptic conditions. Any unused mixture remaining after 24 hours must be discarded. The prepared mixture does not require protection from light.

Instructions for opening ampoules
Before opening the ampoule, ensure that all the solution is in the lower part of the ampoule. Gently shake the ampoule or tap it with your finger to help the solution flow down. Each ampoule has a colored dot (see Figure 1) indicating the score line underneath.

• To open the ampoule, hold it vertically in both hands with the colored dot facing toward you (see Figure 2). The upper part of the ampoule should be gripped so that the thumb is positioned above the colored dot.
• Press as indicated by the arrow in Figure 3. Ampoules are intended for single use only and should be opened immediately before use. Any unused portion of the medicinal product must be discarded according to applicable regulations.

Figure 1.

Figure 2.

Figure 3.

Warnings and precautions
Exercise particular caution when administering the medicinal product to the following patients:

• with respiratory disorders;
• children under 6 months of age and children with unstable cardiovascular systems;
• patients over 60 years of age;
• chronically ill or debilitated patients, e.g., with chronic respiratory insufficiency, chronic renal insufficiency, hepatic function disorders, or cardiac dysfunction;
• patients with renal impairment (creatinine clearance <10 ml/min). The pharmacokinetics of unbound midazolam after intravenous administration are similar to those observed in healthy volunteers. However, during prolonged infusion, the mean duration of sedative effect in patients with renal impairment was significantly longer, most likely due to accumulation of α-hydroxymidazolam glucuronide. There are no data available on patients with severe renal impairment (creatinine clearance below 30 ml/min) receiving midazolam for induction of general anesthesia.
• patients with impaired hepatic function – intravenous midazolam clearance is reduced with prolonged elimination half-life. Therefore, the clinical effect may be stronger and prolonged. In such cases, the midazolam dose should be reduced and the patient's condition closely monitored. Patients at high risk should receive lower doses and be observed for early signs of vital function changes.

Serious adverse reactions affecting the cardiovascular and respiratory systems have been reported: respiratory depression, apnea, respiratory arrest, and (or) cardiac arrest. These events are more likely to occur following too rapid injection or administration of a high dose of the drug.
When midazolam is used for premedication, patients should be observed after administration, as overdosage symptoms may occur due to individual sensitivity differences.
As with other agents that depress the central nervous system and (or) cause muscle relaxation, particular caution is required in patients with myasthenia gravis.
When midazolam and opioids are used concomitantly, the risk of respiratory depression increases; therefore, such cases require close monitoring.

Dosage
Standard dosage
Midazolam is a potent sedative agent that should be administered slowly and incrementally. Gradual administration of midazolam allows safe achievement of the desired level of sedation according to clinical needs, the patient's health status and age, and other concurrently administered drugs. Dosing in patients aged 60 years and older, debilitated or chronically ill patients, and children should be carefully determined, taking into account patient-specific risk factors. Standard dosage recommendations are provided in the table below. Additional information is provided beneath the table.

• CONSCIOUS SEDATION

For diagnostic or therapeutic procedures, midazolam should be administered intravenously. The dose should be individually adjusted and administered gradually. It must not be injected rapidly or given as a single bolus injection. The onset of sedative effect may vary among individual patients depending on the patient's condition and the method of drug administration (e.g., rate of administration, dose size). If necessary and clinically indicated, additional doses may be administered. The drug’s effect begins approximately 2 minutes after administration, with peak effect observed within 5–10 minutes.

Adults: Midazolam should be administered intravenously slowly, at a rate of approximately 1 mg per 30 seconds. In patients under 60 years of age, the initial dose is 2 mg to 2.5 mg, given 5 to 10 minutes before the procedure. If needed, additional doses of 1 mg may be administered. The average total dose ranges from 3.5 mg to 7.5 mg. Usually, a total dose exceeding 5 mg is not necessary. In patients over 60 years of age, debilitated or chronically ill patients, the initial dose given 5 to 10 minutes before the procedure should be reduced to 0.5–1 mg. If necessary, additional doses of 0.5 mg to 1 mg may be administered. In these patients, peak effects are achieved more slowly, and additional doses of midazolam should be administered very slowly and with caution. Usually, a total dose exceeding 3.5 mg is not necessary.

Children: Intravenous route: Midazolam doses should be increased gradually until the desired clinical effect is achieved. The initial dose should be administered over 2 to 3 minutes. Before starting the procedure or repeating the dose, wait 2 to 5 minutes to assess the sedative effect. If deeper sedation is required, continue administering small incremental doses until the appropriate level of sedation is reached.

Infants and young children under 5 years of age may require significantly higher doses (in mg/kg body weight) than older children and adolescents.

Children below 6 months of age – are particularly susceptible to airway obstruction and hypoventilation. Therefore, midazolam is not recommended for sedation in children under 6 months of age.

Children aged 6 months to 5 years: initial dose 0.05 mg/kg to 0.1 mg/kg body weight. Up to 0.6 mg/kg body weight may be required to achieve the desired effect; however, the total dose should not exceed 6 mg. After administration of higher midazolam doses, the risk of hypoventilation and prolonged sedation increases.

Children aged 6 to 12 years: initial dose 0.025 mg/kg to 0.05 mg/kg body weight. A total dose of up to 0.4 mg/kg body weight may be required; maximum dose of 10 mg. After administration of higher midazolam doses, the risk of hypoventilation and prolonged sedation increases.

Children aged 12 to 16 years: dosing as in adults.

Rectal administration: The total dose of midazolam is usually between 0.3 mg/kg and 0.5 mg/kg body weight, administered as a single dose. Rectal administration should be performed using a syringe with a plastic applicator attached. If the volume of solution to be administered is too small, add water to a maximum volume of 10 ml. Repeat rectal dosing is not recommended. Rectal administration of midazolam is not recommended in children below 6 months of age due to limited available data in this patient group.

Intramuscular administration: Doses range from 0.05 mg/kg to 0.15 mg/kg body weight. A total dose greater than 10 mg is usually not necessary. Intramuscular administration should be limited to exceptional circumstances because it is painful. Rectal administration is preferred. In children with body weight below 15 kg, midazolam solution with concentration higher than 1 mg/ml should not be administered. Higher concentrations should be diluted to 1 mg/ml.

• ANESTHESIA

  • Premedication prior to general anesthesia
    Premedication with midazolam administered shortly before the procedure induces sedation (causing drowsiness or sleep and reducing anxiety) and anterograde amnesia in the preoperative period. Midazolam may also be administered together with anticholinergic drugs. In such cases, midazolam should be given intravenously or deep intramuscularly into large muscle groups, 20 to 60 minutes before induction of anesthesia, with rectal administration being the preferred route in children (see below). After administration, continuous and close monitoring of the patient is essential, as sensitivity to the drug varies individually and symptoms of overdose may occur.

Adults: To achieve preoperative sedation and anterograde amnesia, in patients classified as ASA I and II and in patients under 60 years of age, an intravenous dose of 1–2 mg is recommended, which may be repeated as needed, or intramuscular dose of 0.07 mg/kg to 0.1 mg/kg body weight of midazolam. In patients over 60 years of age, debilitated or chronically ill patients, the dose should be reduced and adjusted according to the individual patient's condition.

• Intravenous injection: recommended initial dose is 0.5 mg; if necessary, the dose may be slowly increased.
• Intramuscular injection: 0.025 mg/kg to 0.05 mg/kg body weight.
• When administered concomitantly with narcotic drugs, the dose of midazolam should be reduced. The usual dose is 2 to 3 mg.

Children
Newborns and children below 6 months of age
The use of midazolam is not recommended in children below 6 months of age due to limited data on use.

Children above 6 months of age
Rectal administration: The total dose of midazolam, usually ranging from 0.3 mg/kg to 0.5 mg/kg body weight, should be administered 15 to 30 minutes before induction of anesthesia. Rectal administration should be performed using a syringe with a plastic applicator attached. If the volume to be administered is small, water may be added to a total volume of 10 ml.

Intramuscular administration: Because this route is painful, it should be limited to exceptional circumstances. Rectal administration is recommended. Intramuscular doses that are effective and safe range from 0.08 mg/kg to 0.2 mg/kg body weight.

Children aged 1–15 years require proportionally higher doses compared to adults, relative to body weight.

In children with body weight below 15 kg, midazolam solution with concentration higher than 1 mg/ml should not be administered. Higher concentrations should be diluted to 1 mg/ml.

• Induction of General Anesthesia

Adults: When midazolam is used for induction of anesthesia, individual patient responses may vary. The dose should be administered gradually until the desired effect is achieved, taking into account the patient's age and clinical condition. If midazolam is administered before or simultaneously with other intravenous anesthetic agents or inhaled anesthetics used for induction, the usual initial dose of each agent should be significantly reduced, sometimes down to 25% of the usual initial dose. The desired anesthetic effect is achieved by gradual administration of the drug. The intravenous dose of midazolam used for induction of general anesthesia should be administered slowly and fractionally. Each dose, not exceeding 5 mg, should be injected over 20–30 seconds, with a 2-minute interval between doses.

Patients under 60 years of age who have received premedication: the usual intravenous dose is 0.15 mg/kg to 0.2 mg/kg body weight.

Unpremedicated patients under 60 years of age: a higher dose is required (intravenously 0.3 mg/kg to 0.35 mg/kg body weight). If necessary for complete induction, additional injections of approximately 25% of the initial dose may be administered. Induction may also be completed using inhalational anesthetics. In resistant cases, up to 0.6 mg/kg body weight of midazolam may be administered to achieve induction; however, emergence after such high doses may be prolonged.

Patients over 60 years of age who have received premedication, debilitated or chronically ill patients: the dose should be significantly reduced, e.g., to 0.05–0.15 mg/kg body weight, administered intravenously over 20–30 seconds, with a 2-minute wait for effect.

Unpremedicated patients over 60 years of age: usually require a higher dose of midazolam for induction – an initial dose of 0.15 mg/kg to 0.3 mg/kg body weight is recommended. Patients with severe systemic disease or debilitated patients who have not received premedication usually require a lower dose of midazolam – typically 0.15 mg/kg to 0.25 mg/kg body weight is sufficient.

• Balanced Anesthesia (midazolam as a sedative component)

Adults: Midazolam may be used as a sedative component in balanced anesthesia, administered as repeated small intravenous doses (0.03 mg/kg to 0.1 mg/kg body weight) or by continuous intravenous infusion (0.03 mg/kg/h to 0.1 mg/kg/h), usually in combination with analgesic drugs. Doses and intervals between doses depend on the individual patient response. Lower maintenance doses should be used in patients over 60 years of age, debilitated or chronically ill patients.

• SEDATION IN INTENSIVE CARE UNITS

The desired level of sedation is achieved by gradually increasing the midazolam dose, followed by continuous intravenous infusion or repeated injections, depending on clinical needs, patient condition, age, and concomitant medications.

Adults:
Intravenous loading dose: 0.03 mg/kg to 0.3 mg/kg body weight of midazolam, administered slowly in successive injections. Each single injection of 1 mg to 2.5 mg should be administered over 20 to 30 seconds, with a 2-minute interval between injections. In patients with hypovolemia, vasoconstriction, or hypothermia, the loading dose should be reduced or omitted.

If midazolam is administered together with potent analgesic drugs, these should be given first to safely adjust the sedative effect of midazolam according to the level of sedation induced by the analgesic.

Intravenous maintenance dose: 0.03 mg/kg/h to 0.2 mg/kg/h.
In patients with hypovolemia, vasoconstriction, or hypothermia, the maintenance dose should be reduced. The level of sedation should be regularly assessed. During prolonged sedation, tolerance may develop, requiring an increase in dose.

Children
Newborns and infants up to 6 months of age
Midazolam should be administered as a continuous intravenous infusion, starting at 0.03 mg/kg/h (0.5 μg/kg/min) in newborns with a gestational age below 32 weeks, or 0.06 mg/kg/h (1 μg/kg/min) in newborns with a gestational age above 32 weeks and infants up to 6 months of age.

Loading doses are not recommended in preterm infants, newborns, and infants under 6 months of age. The drug should be administered by infusion, initially at a faster rate during the first few hours to achieve therapeutic plasma concentrations. The infusion rate should be carefully and frequently monitored, especially during the first 24 hours, to administer the lowest effective dose and prevent potential drug accumulation. Close observation of respiratory function and monitoring of blood oxygen saturation are recommended.

Children above 6 months of age
In children above 6 months of age who are intubated and mechanically ventilated, a loading dose of 0.05 mg/kg to 0.2 mg/kg body weight should be administered intravenously slowly over 2 to 3 minutes until the desired clinical effect is achieved.

Midazolam should not be administered as a rapid intravenous bolus. After the loading dose, a continuous intravenous infusion of 0.06 mg/kg/h to 0.12 mg/kg/h (1 to 2 μg/kg/min) should be initiated. The infusion rate may be increased or decreased as needed (usually by 25% of the initial or subsequent rate), or additional intravenous doses of midazolam may be administered to increase or maintain the drug effect at the desired level.

When initiating midazolam administration in patients with impaired cardiovascular function, the drug should be administered in small incremental injections, with careful observation for signs of hemodynamic instability, such as arterial hypotension.

Such patients are also susceptible to the respiratory depressant effects of midazolam and require particularly careful monitoring of respiratory function and blood oxygen saturation.

Midazolam solution with a concentration greater than 1 mg/ml should not be used in preterm infants, newborns, and children with body weight below 15 kg. Higher concentrations should be diluted to 1 mg/ml.