Mizormic

Package Leaflet: Information for the Patient

Mizormic, 5 mg/ml, Solution for Injection

Midazolam Hydrochloride

Read the Package Leaflet Carefully Before Using the Medication, as it Contains Important Information for the Patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor, pharmacist, or nurse. See section 4.

Table of Contents of the Leaflet:

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

1. What is Mizormic and what is it used for

Mizormic (midazolam) is a short-acting sedative belonging to a group of medicines called benzodiazepines.

Mizormic is used:

• for inducing shallow sedation (a state of relaxation or drowsiness while maintaining consciousness) in adults and children,
• for inducing sedation in adults and children in intensive care units,
• for anesthesia in adults (premedication before induction of anesthesia, induction of anesthesia, as a sedative component with other medications used in anesthesia),
• for premedication before induction of anesthesia in children.

2. Important information before using Mizormic

When not to use Mizormic

• if the patient is allergic to midazolam, other benzodiazepines, or any of the other ingredients of Mizormic (listed in section 6),
• if the patient has severe respiratory failure or acute respiratory depression - in the case of shallow sedation.

Warnings and precautions

When using Mizormic for premedication, the patient's reactions will be closely monitored to ensure the administration of the appropriate dose of the medication due to the varying sensitivity of patients. When using Mizormic, paradoxical reactions and anterograde amnesia (forgetting recent events) have been reported (see section 4 "Possible side effects"). Particular caution should be exercised if:

• the patient is over 60 years old,
• the patient is chronically ill or debilitated (e.g., the patient has chronic respiratory failure, chronic renal failure, liver dysfunction, or heart disease),
• the patient has muscle weakness (severe neuromuscular disease characterized by muscle weakness),
• the patient has a history of alcohol or drug abuse,
• the patient is taking any other medications, including those available without a prescription (more information - see the section "Mizormic and other medications"),
• the patient is pregnant or suspects she may be pregnant.

Chronic treatment
In the event of chronic use of Mizormic in a patient, tolerance to the medication may develop (Mizormic becomes less effective) or dependence on the medication. After completing long-term treatment (such as in an intensive care unit), the patient may experience the following withdrawal symptoms: headaches, muscle pain, anxiety symptoms, tension, restlessness, psychomotor agitation, disorientation, irritability, insomnia, mood changes, hallucinations, and seizures. To prevent these symptoms, the doctor will gradually reduce the dose of the medication.

Children and adolescents

Particular caution should be exercised when using Mizormic in children, especially those under 6 months old (including newborns and premature babies). You should inform your doctor if your child has cardiovascular disease. In such cases, the child will be closely monitored, and the dose will be modified accordingly.

Mizormic and other medications

You should tell your doctor about all medications you are currently taking or have recently taken, as well as any medications you plan to take. This is very important because taking multiple medications at the same time can enhance or weaken the effects of the medications being taken. The effect of Mizormic may be enhanced by the following medications:

• neuroleptics, sedatives, tranquilizers,
• antidepressants,
• opioid analgesics (very strong painkillers),
• anesthetics,
• certain medications used to treat allergies (antihistamines),
• medications used to treat fungal infections (ketokonazole, voriconazole, fluconazole, itraconazole, posaconazole),
• antibiotics (erythromycin, clarithromycin),
• medications used to treat high blood pressure (diltiazem),
• medications used to treat HIV infection (saquinavir and other HIV protease inhibitors),
• medications used to lower cholesterol levels (atorvastatin).

Concomitant use of Mizormic and opioids (strong painkillers, medications used for substitution therapy for addiction, and some cough medications) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and can be life-threatening. For this reason, concomitant use should only be considered when other treatment options are not possible. If, however, the doctor prescribes Mizormic together with opioids, they should limit the dose and duration of concomitant treatment. You should inform your doctor about all opioids you are taking and strictly follow their instructions. It may be helpful to inform friends or relatives about these symptoms. In case of such symptoms, you should contact your doctor. The effect of Mizormic may be reduced by the following medications:

• medications used to treat tuberculosis, such as rifampicin,
• preparations of St. John's Wort (a herbal remedy used to treat depression).

Using Mizormic with food, drink, and alcohol

Alcohol may enhance the sedative effect of Mizormic and should therefore be avoided during treatment.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor or pharmacist for advice before taking this medication. Midazolam may pass into breast milk, so breastfeeding women should not breastfeed for 24 hours after taking Mizormic.

Driving and using machines

Mizormic may cause drowsiness, memory disturbances, reduced concentration, and coordination. These symptoms may adversely affect the ability to perform activities that require precision, such as driving or operating machinery. After taking Mizormic, the patient should not drive or operate machinery until the effects of the medication have completely worn off. The doctor will decide when the patient can resume these activities. After therapy, the patient should return home accompanied by another person.

Mizormic contains sodium

Mizormic contains less than 1 mmol of sodium (23 mg) per dose, which means the medication is considered "sodium-free".

3. How to use Mizormic

Mizormic should only be administered by experienced doctors and by persons with appropriate training in recognizing and treating expected adverse reactions in a fully equipped facility with equipment for monitoring and supporting respiratory and cardiovascular functions.

Dosage and administration

The appropriate dose for a given patient is determined by the doctor. Doses vary and depend on the planned treatment and desired level of sedation. The dose that the patient receives also depends on body weight, age, overall health, response to the medication, and the need for concomitant use of other medications. If the patient will require strong painkillers, they will be administered first, and then Mizormic will be administered in an appropriately adjusted dose. Mizormic is administered slowly - by injection into a vein (intravenous administration), by infusion (intravenous infusion), by intramuscular injection (intramuscular administration), or by rectal administration.

Overdose of Mizormic

This medication will be administered by a doctor. If the patient accidentally overdoses, it may lead to drowsiness, clumsiness (problems with coordination and balance), speech disturbances, and involuntary eye movements, loss of reflexes, apnea, low blood pressure, respiratory and cardiovascular depression (slowing and shallowing of breathing and slowing of heart rate), and coma. Overdose may require close monitoring of vital signs and treatment of symptoms of respiratory and cardiovascular disturbances, as well as the use of a medication with antagonistic effects to benzodiazepines (a medication that reduces the effect of midazolam). In case of any further doubts about the use of this medication, you should consult a doctor or pharmacist.

4. Possible side effects

Like all medications, Mizormic can cause side effects, although not everybody gets them. You should stop using Mizormic and immediately inform your doctor if you experience any of the following side effects, which may be life-threatening and may require immediate treatment:

• anaphylactic shock (a life-threatening allergic reaction). Symptoms may include sudden rash, itching, or hives and swelling of the face, lips, tongue, or other parts of the body. The patient may also experience shortness of breath, wheezing, or breathing difficulties, or pallor, weak and rapid pulse, or feeling of loss of consciousness. Additionally, there may be chest pain, which can be a sign of a serious allergic reaction called Kounis syndrome.
• generalized allergic reactions (skin reactions, reactions affecting the heart and circulatory system, such as low blood pressure, wheezing)
• shortness of breath and breathing difficulties (sometimes leading to respiratory arrest), apnea.
• laryngospasm causing choking.
• cardiac arrest (the heart stops beating). Symptoms include loss of consciousness associated with lack of pulse.

The following side effects have also been reported in connection with the use of this medication:

• disorientation, euphoria, hallucinations
• paradoxical reactions (opposite of expected) occurring mainly in children and the elderly: excitement, involuntary movements of the body, including muscle tension and tremors, excessive activity, hostility, anger, aggression, seizures, and physical aggression
• physical dependence on the medication, withdrawal symptoms, including seizures
• prolonged sedation, reduced alertness, drowsiness, headache, dizziness, coordination and balance problems
• transient amnesia (the patient does not remember events that occurred shortly after administration of the medication, the duration of amnesia depends on the dose of the medication)
• seizures in premature infants and newborns
• low blood pressure, slow heart rate, vasodilation (manifested as flushing, fainting, and headache)
• hiccups
• nausea, vomiting, constipation, dry mouth
• skin rash, hives, itching
• fatigue
• redness and pain at the injection site, thrombophlebitis, thrombosis (blood clots in the veins)
• falls, fractures.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, you should inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of the medication.

5. How to store Mizormic

Keep out of sight and reach of children. Do not use this medication after the expiry date stated on the carton and label after EXP. The expiry date refers to the last day of the month stated. The abbreviation "Lot" means batch number. Do not store above 25°C. Do not freeze. Store in the original packaging to protect from light. Medications should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medications that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Mizormic contains

• The active substance of Mizormic is midazolam. 1 ml of the solution contains 5 mg of midazolam (in the form of hydrochloride).
• The other ingredients are sodium chloride, hydrochloric acid, sodium hydroxide, and water for injections.

What Mizormic looks like and contents of the pack

Clear, colorless solution, without visible particles. Colorless ampoules made of neutral glass type I, packed in cardboard boxes. Pack sizes: 10 ampoules of 1 ml, 3 ml, or 10 ml.

Marketing authorization holder and manufacturer

Marketing authorization holder

Bausch Health Ireland Limited, 3013 Lake Drive, Citywest Business Campus, Dublin 24, D24PPT3, Ireland, Tel: +48 17 865 51 00

Manufacturer

HBM Pharma s.r.o., Sklabinska 30, 036 80 Martin, Slovakia

Date of last revision of the leaflet: -------------------------------------------------------------------------------------------------------------------------

Information intended for healthcare professionals only:

Standard dosing

Midazolam is a potent sedative that requires individual dose titration and slow administration. It is recommended to titrate the dose individually for each patient to ensure safe achievement of the desired level of sedation, taking into account the patient's clinical condition, physical status, age, and concomitant medications. In adults over 60 years old, debilitated or chronically ill patients, and children and adolescents, the dose should be titrated with caution and taking into account individual risk factors. Typical dosing is presented in the table below. Additional detailed information is provided in the text following the table.

Dosing for shallow sedation

To achieve shallow sedation before diagnostic or surgical intervention, midazolam is administered intravenously. The dose must be individually titrated and, if necessary, slowly increased - it should not be administered quickly or as a single bolus. The onset of sedative effect of the medication becomes apparent at different times after administration - depending on the patient's physical condition and specific circumstances of administration (e.g., the speed at which the medication was administered, the size of the dose). If necessary, additional doses of the medication can be administered, depending on individual needs. The onset of action becomes apparent after about 2 minutes after injection. The maximum effect is achieved within about 5-10 minutes. Adults: Intravenous injection of midazolam should be performed slowly, at a rate of about 1 mg per 30 seconds. In adults under 60 years old, the initial dose is 2.0-2.5 mg administered 5-10 minutes before the start of the procedure. If necessary, additional doses of 1 mg can be administered. It has been found that, on average, a total dose of 3.5-7.5 mg is administered. Usually, it is not necessary to use a total dose exceeding 5 mg. In adults over 60 years old and in debilitated or chronically ill patients, the initial dose should be reduced to 0.5-1.0 mg administered 5-10 minutes before the start of the procedure. If necessary, additional doses of 0.5-1.0 mg can be administered. Since the maximum effect may be achieved more slowly in these patients, additional doses of midazolam should be administered at much longer intervals and with caution. Usually, it is not necessary to exceed a total dose of 3.5 mg. Children: Intravenous administration. The dose of midazolam should be increased slowly to achieve the desired clinical effect. The initial dose of midazolam should be administered over 2-3 minutes. Before starting the procedure or administering an additional dose, you should wait an additional 2-5 minutes to assess the full sedative effect. If deeper sedation is required, the dose should be increased in small increments to achieve the appropriate level of sedation. Infants and young children under 5 years old may require significantly higher doses per kilogram of body weight than older children and adolescents.

• Children under 6 months: children under 6 months are particularly prone to airway obstruction and hypoventilation. Therefore, the use of midazolam for shallow sedation in children under 6 months is not recommended.
• Children from 6 months to 5 years: the initial dose is 0.05-0.10 mg/kg body weight. To achieve the desired effect, it may be necessary to use a total dose of up to 0.6 mg/kg body weight, but the total dose should not exceed 6 mg. The use of higher doses may be associated with prolonged sedation and the risk of hypoventilation.
• Children from 6 to 12 years: the initial dose is 0.025-0.050 mg/kg body weight. It may be necessary to use a total dose of up to 0.4 mg/kg body weight, with a maximum of 10 mg. The use of higher doses may be associated with prolonged sedation and the risk of hypoventilation.
• Children and adolescents from 12 to 16 years: dosing is the same as for adults.

Rectal administration. The total dose of midazolam usually ranges from 0.3 to 0.5 mg/kg body weight. Rectal administration of the solution from the ampoule should be performed using a plastic applicator attached to the end of the syringe. If the volume of the solution to be administered is too small, it can be diluted with water to a total volume of 10 ml. The total dose should be administered once - repeated rectal administration should be avoided. The use of this method is not recommended in children under 6 months, as the data for this population are limited. Intramuscular administration. The doses used range from 0.05 to 0.15 mg/kg body weight. Usually, it is not necessary to use a total dose exceeding 10 mg. This route of administration should be used in exceptional cases. Rectal administration is preferred, as intramuscular administration is painful. Children with a body weight of less than 15 kg should not be given midazolam solutions with a concentration exceeding 1 mg/ml. Solutions with a higher concentration should be diluted to a concentration of 1 mg/ml.

Dosing for anesthesia

Pre-anesthetic medication

Pre-anesthetic medication with midazolam administered immediately before the procedure induces sedation (induces drowsiness or drowsiness and reduces anxiety) and preoperative amnesia. Midazolam can also be administered in combination with anticholinergics. In this indication, midazolam should be administered intravenously or intramuscularly (deeply into a large muscle) 20-60 minutes before the induction of anesthesia, while in children, the preferred route of administration is rectal (see below). After premedication, it is obligatory to closely monitor the patient's condition, as sensitivity to the medication is individually variable and symptoms of overdose may occur. Adults: The recommended dose for preoperative sedation and to induce amnesia of preoperative events in adults with ASA physical status I and II under 60 years old is 1-2 mg intravenously (which can be repeated if necessary) or 0.07-0.10 mg/kg body weight intramuscularly. In patients over 60 years old, debilitated, or chronically ill, the dose should be reduced and individually adjusted. The recommended initial dose intravenously is 0.5 mg, which can be slowly increased if necessary. Intramuscularly, the recommended dose is 0.025-0.050 mg/kg body weight. When administered with narcotic medications, the dose of midazolam should be reduced. Usually, a dose of 2-3 mg is used. Children and adolescents: Newborns and infants under 6 months: The use of midazolam is not recommended in children under 6 months, as the available data are limited. Children over 6 months: Rectal administration: the total dose, usually in the range of 0.3-0.5 mg/kg body weight, should be administered 15-30 minutes before the induction of anesthesia. Rectal administration of the solution from the ampoule should be performed using a plastic applicator attached to the end of the syringe. If the volume of the solution to be administered is too small, it can be diluted with water to a total volume of 10 ml. Intramuscular administration: due to the pain associated with intramuscular administration, this route should only be used in exceptional cases. It is recommended to prefer the rectal route. However, it has been shown that midazolam administered intramuscularly in doses ranging from 0.08 to 0.20 mg/kg body weight is effective and safe. In children from 1 to 15 years old, it is necessary to use proportionally higher doses than in adults per kilogram of body weight. Children with a body weight of less than 15 kg should not be given midazolam solutions with a concentration exceeding 1 mg/ml. Solutions with a higher concentration should be diluted to a concentration of 1 mg/ml.

Induction of anesthesia

Adults: If midazolam is used for the induction of anesthesia before the administration of other anesthetic medications, the patient's reaction is individually variable. The dose should be slowly increased to achieve the desired effect, taking into account the patient's age and clinical condition. When midazolam is administered before or in combination with other intravenous or inhaled medications used for the induction of anesthesia, the initial dose of each should be significantly reduced, even to 25% of the usual initial dose. The desired level of anesthesia is achieved by slowly increasing the dose. The dose of midazolam administered intravenously for the induction of anesthesia should be administered slowly, in small increments. Doses should not be increased by more than 5 mg administered over 20-30 seconds, with a 2-minute interval between consecutive doses.

• In adults under 60 years old who have been premedicated, an intravenous dose of 0.15-0.20 mg/kg body weight is usually sufficient.
• In adults under 60 years old who have not been premedicated, the dose may be higher (0.30-0.35 mg/kg body weight intravenously). If necessary, to complete the induction, doses increased by about 25% of the initial dose administered to the patient can be given. Induction can also be completed using inhaled anesthetics. In resistant cases, a total dose of up to 0.6 mg/kg body weight can be used, but such high doses will prolong the recovery process.
• In adults over 60 years old who have been premedicated, and in debilitated or chronically ill patients, the dose should be significantly reduced, e.g., to a dose in the range of 0.05-0.15 mg/kg body weight administered intravenously over 20-30 seconds, with a 2-minute interval to assess the effect.
• In adults over 60 years old who have not been premedicated, usually a higher dose of midazolam is required to induce anesthesia. It is recommended to use an initial dose of 0.15-0.30 mg/kg body weight. Patients with severe systemic disease or debilitation who have not been premedicated usually require smaller doses of midazolam to induce anesthesia. An initial dose of 0.15-0.25 mg/kg body weight is usually sufficient.

Sedative component in combined anesthesia

Adults: Midazolam can be used as a sedative component in combined anesthesia, in the form of intermittent intravenous doses (in the range of 0.03-0.10 mg/kg body weight) or continuous intravenous infusion (in the range of 0.03-0.10 mg/kg body weight/h), usually in combination with analgesics. The dose and intervals between consecutive doses depend on the individual patient's response. In adults over 60 years old and in debilitated or chronically ill patients, it will be necessary to use smaller maintenance doses.

Sedation in ICU

The intended level of sedation is achieved by slowly increasing the dose of midazolam, and then continuous infusion or repeated boluses - depending on clinical needs, patient condition, age, and concomitantly used medications. Adults: Intravenous loading dose: 0.03-0.30 mg/kg body weight, which should be administered slowly in divided doses. Each divided dose, in the range of 1.0-2.5 mg, should be administered over 20-30 seconds, waiting 2 minutes before administering the next dose. In patients with hypovolemia, vasoconstriction, or hypothermia, the loading dose should be smaller or omitted. When midazolam is administered in combination with potent analgesics, the analgesics should be administered first, so that the sedative effect of midazolam can be safely titrated to the potential sedative effect of the analgesics. Intravenous maintenance dose: doses may range from 0.03 to 0.20 mg/kg body weight/h. In patients with hypovolemia, vasoconstriction, or hypothermia, the maintenance dose should be reduced. The level of sedation should be regularly monitored. In the case of prolonged sedation, tolerance may develop, requiring an increase in dose. Newborns and infants under 6 months: Midazolam should be administered as a continuous intravenous infusion, starting from a dose of 0.03 mg/kg body weight/h (0.5 micrograms/kg body weight/min) in the case of newborns born before 32 weeks of gestation or from a dose of 0.06 mg/kg body weight/h (1 microgram/kg body weight/min) in the case of newborns born after 32 weeks of gestation and children under 6 months. In newborns and infants under 6 months, intravenous loading doses should not be used - instead, the infusion can be started at a higher rate for the first few hours to achieve a therapeutic concentration of the medication in the blood. The infusion rate should be carefully and frequently evaluated, especially after the first 24 hours, so that the smallest effective dose is administered and the risk of medication accumulation in the body is reduced. It is necessary to closely monitor respiratory rate and oxygen saturation. Children over 6 months: In intubated and mechanically ventilated pediatric patients, to achieve the desired clinical effect, an intravenous loading dose of 0.05-0.20 mg/kg body weight should be administered slowly over at least 2-3 minutes. Midazolam should not be administered as a rapid intravenous injection. After administering the loading dose, a continuous intravenous infusion should be started at a dose of 0.06-0.12 mg/kg body weight/h (1-2 micrograms/kg body weight/min). If necessary, the infusion rate can be increased or decreased (usually by 25% of the initial or subsequent rate) or additional intravenous doses of midazolam can be administered to increase or maintain the desired effect. When starting the infusion of midazolam in hemodynamically unstable patients, the loading dose usually used can be gradually increased, and the patient should be monitored for signs of hemodynamic instability, such as hypotension. These patients are also prone to midazolam-induced respiratory depression and require close monitoring of respiratory rate and oxygen saturation. In premature infants, newborns, and children with a body weight of less than 15 kg, midazolam solutions with a concentration exceeding 1 mg/ml should not be used. Solutions with a higher concentration should be diluted to a concentration of 1 mg/ml.

Patients with renal impairment

In patients with renal impairment (creatinine clearance <10 ml min), the pharmacokinetics of free midazolam after single intravenous administration is similar to that in healthy volunteers. however, during prolonged infusion patients intensive care units (icu), mean duration sedative effect with renal impairment was significantly longer, most likely due accumulation α-hydroxymidazolam glucuronide. there are no specific data on severe (creatinine clearance below 30 min) receiving for induction anesthesia.< p>

Patients with hepatic impairment

Hepatic impairment reduces the clearance of intravenously administered midazolam, prolonging the elimination half-life. This may therefore lead to increased and prolonged clinical effects of the product. The required dose of midazolam can be reduced, with appropriate monitoring of vital signs.

Patients of advanced age and children and adolescents

See the table above.

Special warnings and precautions for use

Midazolam should only be administered by experienced physicians in a facility fully equipped with monitoring and life-support equipment and by personnel trained in the recognition and treatment of expected adverse effects, including respiratory and cardiac resuscitation. Severe adverse effects have been reported, including respiratory and cardiac effects. These effects included respiratory depression, apnea, respiratory arrest, and/or cardiac arrest. The risk of such life-threatening events is greater with too rapid administration or excessive dosing. Particular caution is necessary when using shallow sedation in patients with respiratory function disorders. Infants under 6 months of age are particularly sensitive to airway obstruction and hypoventilation, and it is essential to increase the dose in small increments to achieve the desired clinical effect and to carefully monitor respiratory rate and oxygen hemoglobin saturation. After administration of midazolam as premedication, it is essential to monitor the patient's condition, as sensitivity to the drug can vary and signs of overdose may occur. Particular caution is necessary when administering midazolam to high-risk patients, including:

• adults over 60 years of age,
• patients with chronic diseases or debilitation, such as patients with chronic respiratory failure, chronic renal failure, liver function disorders, or cardiac function disorders,
• children and adolescents, particularly unstable cardiovascular patients.

Patients in these high-risk groups require lower doses (see above) and should be continuously monitored for early signs of decreased vital functions. As with all substances that can cause CNS depression and/or skeletal muscle relaxation, particular caution is necessary when using midazolam in patients with muscle weakness (myasthenia gravis). Tolerancehas been reported to midazolam when used for long-term sedation in intensive care units (ICUs). Dependenceshould not be forgotten when using midazolam for long-term sedation in ICU patients, as dependence may develop in these patients. The risk of dependence increases with dose and duration of treatment and is also greater in patients with a history of alcohol or drug abuse. Withdrawal symptomsmay occur when midazolam is used for prolonged periods in ICU patients, and physical dependence may develop. Abrupt discontinuation of the drug may cause withdrawal symptoms, including headache, muscle pain, anxiety symptoms, tension, restlessness, psychomotor agitation, disorientation, irritability, insomnia with rebound, mood changes, hallucinations, and seizures. Since the risk of withdrawal symptoms is greater with abrupt discontinuation, gradual dose reduction is recommended. Amnesiais a common effect of midazolam (often a desirable effect before or during surgical procedures and diagnostic tests), and its duration is directly proportional to the dose administered. Prolonged amnesia may be a problem in outpatients who are scheduled for discharge immediately after the procedure. After parenteral administration of midazolam, the patient should only be discharged from the hospital or clinic in the company of an escort. Paradoxical reactionshave been reported with midazolam, including psychomotor excitement, involuntary movements (including tonic-clonic seizures and muscle tremors), overactivity, hostility, rage, aggressive behavior, and violent behavior. These reactions may occur with high doses and/or rapid injection, and the highest frequency has been reported in children and the elderly. Reduced midazolam eliminationmay occur with concomitant administration of substances that inhibit or induce CYP3A4, and dose adjustment may be necessary. Elimination of midazolam may also be delayed in patients with liver function disorders, low cardiac output, and neonates. Preterm and term newbornsrequire particular caution during sedation, as they are at increased risk of apnea. It is essential to carefully monitor respiratory rate and oxygen hemoglobin saturation. In newborns, rapid injection of the drug should be avoided. Newborns have reduced and/or immature organ function and are sensitive to the excessive and/or prolonged effects of midazolam. In unstable cardiovascular pediatric patients, adverse effects on the cardiovascular system have been observed, and rapid intravenous administration should be avoided. Infants under 6 months of agemay only receive midazolam for sedation in an ICU setting. Infants under 6 months of age are particularly sensitive to airway obstruction and hypoventilation, and it is essential to increase the dose in small increments to achieve the desired clinical effect and to carefully monitor respiratory rate and oxygen hemoglobin saturation (see above, "Preterm and term newborns"). Concomitant use of alcohol/substances with depressive effects on the CNSshould be avoided, as these substances may enhance the clinical effects of midazolam, including sedation or respiratory depression. History of alcohol or drug abuseis a contraindication to the use of midazolam and other benzodiazepines. Discharge criteriaafter administration of midazolam require that the patient may only be discharged from the hospital or clinic after the decision has been made by the attending physician and in the company of an escort. It is recommended that the patient be accompanied by a second person after discharge.