MIDAZOLAM NORMON 1 mg/ml INJECTABLE SOLUTION AND PERFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Midazolam Normon 1 mg/ml Solution for Injection and Infusion EFG

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

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

Contents of the pack

1. What is Midazolam Normon and what is it used for
2. What you need to know before you use Midazolam Normon
3. How to use Midazolam Normon
4. Possible side effects
5. Storing Midazolam Normon
6. Contents of the pack and other information

1. What is Midazolam Normon and what is it used for

The active substance of Midazolam Normon is midazolam. It belongs to the group of benzodiazepines, drugs called hypnotics (sleep inducers) and sedatives (drugs that decrease nervous excitement).

Midazolam is indicated:

In adults for:

• Conscious sedationbefore and during diagnostic or therapeutic procedures with or without local anesthesia.
• Anesthesia:

Premedication before induction of anesthesia.

Induction of anesthesia.

As a sedative component in combined anesthesia.

• Sedation in Intensive Care Units (ICU).

In children for:

• Conscious sedationbefore and during diagnostic or therapeutic procedures with or without local anesthesia.
• Anesthesia:Premedication before induction of anesthesia.
• Sedation in Intensive Care Units (ICU).

2. What you need to know before you use Midazolam Normon

This medicine should only be used when adequate resuscitation equipment is available for each type of patient, as intravenous administration of this medicine can depress myocardial contractility (decrease heart contractions) and cause apnea (pause in breathing).

Do not use Midazolam Normon

• If you are allergic to midazolam, benzodiazepines, or any of the other components of this medicine (listed in section 6).
• In conscious sedation if the patient has severe respiratory insufficiency or acute respiratory depression.

Warnings and precautions

Consult your doctor or nurse before starting to use this medicine, if it is administered in:

• Adults over 60 years old.

• Pediatric patients, especially those with cardiovascular instability.
• Patients with chronic diseases or weakened, such as:

• Patients with chronic respiratory insufficiency.
• Patients with chronic renal insufficiency.
• Patients with altered cardiac function.
• Patients with altered hepatic function.
• Patients with myasthenia gravis (severe muscle weakness).

These high-risk patients require lower doses and should be continuously monitored to detect early signs of alterations in vital functions.

• Patients with a history of alcohol or drug abuse.

• Patients for premedication, it is mandatory to closely observe the patient after administration because individual sensitivity is variable and symptoms of overdose may occur.

Also, the following aspects that may occur while being treated with this medicine should be taken into account:

Tolerance:

A certain decrease in efficacy has been described when midazolam is used for prolonged sedation in intensive care units (ICU).

Dependence:

When midazolam is used for prolonged sedation in the ICU, it should be taken into account that it can produce physical dependence. The risk of dependence increases with the dose and duration of treatment.

Withdrawal symptoms:

During prolonged treatment with midazolam in the ICU, physical dependence may occur. Therefore, abrupt interruption of treatment will be accompanied by withdrawal symptoms. The following symptoms may occur: headache, myalgias (muscle pains), anxiety, tension, restlessness, confusion, irritability, insomnia, mood changes, hallucinations, and convulsions. As the risk of withdrawal symptoms is higher after sudden interruption of treatment, it is recommended to gradually decrease the doses (see section 3).

Amnesia:

Midazolam causes anterograde amnesia (partial or total loss of memory related to what happened, just after recovery of consciousness; often this effect is very desirable in situations such as before and during surgical interventions and diagnostic procedures), whose duration is directly related to the administered dose. Prolonged amnesia may pose problems in the case of outpatient patients, for whom discharge is planned after the procedure. After receiving midazolam by parenteral route, patients may leave the hospital or office only if accompanied by another person.

Paradoxical reactions:

Paradoxical reactions have been described with midazolam, such as agitation, involuntary movements (tonic/clonic movements and muscle tremors), hyperactivity, hostility, anger, aggression, paroxysmal excitement, and threats and insults. These reactions may occur with high doses or when the injection is administered rapidly. Such reactions are characterized by a maximum incidence in the case of children and the elderly.

Children and adolescents

It is not recommended to use for children under 6 months in conscious sedation and anesthesia.

Other medicines and Midazolam Normon

Tell your doctor if you are using, have recently used, or may need to use any other medicine.

Certain medicines may interact with midazolam; in these cases, it may be necessary to change the dose or interrupt treatment with one of them.

It is important that you inform your doctor if you are taking or have recently taken any of the following medicines:

• Itraconazole, fluconazole, and ketoconazole (drugs for the treatment of fungal infections).
• Verapamil and diltiazem (calcium antagonist drugs).
• Erythromycin and clarithromycin (macrolide antibiotics).
• Cimetidine and ranitidine (drug for the treatment of gastroduodenal ulcer).
• Saquinavir and other protease inhibitors (drugs used in the treatment of HIV infection (AIDS)).
• Central nervous system depressants (opioids, antipsychotics, and other benzodiazepines).
• Opioids, phenobarbital, and benzodiazepines. It is necessary to monitor especially for an additional increase in respiratory depression in the case of treatment with these drugs together with Midazolam.

Additional sedation should be taken into account when midazolam is combined with sedative drugs.

The intravenous administration of midazolam decreases the minimum alveolar concentration (MAC) of inhalation anesthetics necessary for general anesthesia.

Taking Midazolam Normon with food, drinks, and alcohol

Alcohol can significantly enhance the sedative effect of midazolam. Alcohol consumption should be avoided when midazolam is administered.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Pregnancy

Midazolam should not be used during pregnancy unless absolutely necessary. It is preferable not to use it for cesarean sections.

The risk to the fetus should be taken into account when administering midazolam for any surgical intervention near the end of pregnancy.

Breastfeeding

Mothers who are breastfeeding should suspend it until 24 hours after the administration of midazolam.

Driving and using machines

Midazolam is a medicine that causes sleepiness. Do not drive or use machines if you feel drowsy or if you notice that your attention and reaction capacity are reduced. Pay special attention at the start of treatment or if the dose is increased.

Your doctor will decide when you can resume these activities.

It is recommended that the patient be accompanied when returning home after discharge.

Midazolam Normon contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per ampoule; this is, essentially "sodium-free".

3. How to use Midazolam Normon

Follow exactly the administration instructions of this medicine indicated by your doctor. In case of doubt, consult your doctor again. Your doctor will indicate the duration of your treatment with Midazolam Normon.

Midazolam is a potent sedative that requires dose adjustment and slow administration. Your doctor will adjust the dose according to clinical needs, physical condition, age, weight, and concomitant medications.

Midazolam Normon can be administered as an intravenous bolus, intravenous infusion, intramuscular injection, and rectally.

If you use more Midazolam Normon than you should

Symptoms:

The symptoms of overdose are: drowsiness, mental confusion, lethargy, and muscle relaxation or paradoxical excitement. The most severe symptoms would consist of areflexia (absence of normal reflexes), hypotension, cardiorespiratory depression, apnea (pause in breathing), and coma.

If you take more Midazolam Normon than you should, consult your doctor or pharmacist immediately.

In case of overdose or accidental ingestion, consult the Toxicological Information Service. Telephone (91) 562 04 20.

Treatment in case of overdose:

In most cases, it is only necessary to monitor vital functions. In the treatment of overdose, special attention should be paid to respiratory and cardiovascular functions in the intensive care unit (ICU).

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Side effects can occur with certain frequencies, which are defined below:

Very common (may affect more than 1 in 10 people).

Common (may affect up to 1 in 10 people).

Uncommon (may affect up to 1 in 100 people).

Rare (may affect up to 1 in 1,000 people).

Very rare (may affect up to 1 in 10,000 people).

Frequency not known (cannot be estimated from the available data).

The following adverse reactions have been described (very rarely) when administering midazolam:

Disorders of the skin and subcutaneous tissue: skin rash (redness of the skin), urticaria (allergy), itching, swelling of the face, lips, tongue, or throat that makes swallowing or breathing difficult.

Disorders of the central and peripheral nervous system and psychiatric disorders: prolonged sedation and drowsiness, decreased alertness, confusion, euphoria, hallucinations, fatigue, headache, dizziness, ataxia (lack of coordination), postoperative sedation, and anterograde amnesia (whose duration is directly related to the administered dose). Anterograde amnesia may persist at the end of the procedure, and in isolated cases, prolonged amnesia has been described.

Paradoxical reactions have been described, such as agitation, involuntary movements (tonic/clonic movements and muscle tremors), hyperactivity, hostility, anger, aggression, paroxysmal excitement, and threats and insults, particularly in children and the elderly.

Convulsions have been reported more frequently in infants and premature newborns.

The use of midazolam, even in therapeutic doses, can favor the development of physical dependence after prolonged intravenous administration; the abrupt interruption of the drug can be accompanied by withdrawal symptoms, such as convulsions.

Disorders of the gastrointestinal tract: nausea, vomiting, hiccups, constipation, and dry mouth.

Cardiovascular disorders: serious cardiovascular adverse events: respiratory depression, apnea (pause in breathing), cardiac arrest, hypotension, alteration of heart rate, vasodilatory effects, dyspnea (feeling of lack of air), and laryngospasm. Potentially fatal incidents are more likely in adults over 60 years old and those patients with pre-existing respiratory insufficiency or altered cardiac function, particularly when the injection is administered too quickly or when a high dose is applied.

General disorders: generalized allergic reactions: skin reactions, cardiovascular reactions, bronchospasm, anaphylactic shock (severe allergic reaction).

Stop taking Midazolam Normon and go to the doctor immediately if you notice any of the following side effects. They can be potentially fatal and may require urgent medical treatment:

• Anaphylactic shock (a potentially fatal allergic reaction). The signs may include a sudden rash, itching, or urticaria, and swelling of the face, lips, tongue, or other parts of the body. You may also have shortness of breath, wheezing, or breathing difficulties, or pale skin, weak and rapid pulse, or feeling of loss of consciousness. Additionally, you may experience chest pain, which can be a sign of a severe allergic reaction called Kounis syndrome.

Disorders at the injection site: erythema (redness) and pain at the injection site, circulatory disorders (thrombophlebitis and thrombosis).

Reporting of side effects

If you experience any side effects, talk to your doctor, nurse, or pharmacist, even if it is possible side effects not listed in this leaflet.

You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Midazolam Normon

Keep this medicine out of the sight and reach of children.

Do not freeze. A precipitate may form that dissolves when the contents are shaken at room temperature.

Do not use this medicine after the expiration date that appears on the packaging after EXP. The expiration date is the last day of the month indicated.

6. Packaging Contents and Additional Information

Composition of Midazolam Normon 1 mg/ml injectable and infusion solution

• The active ingredient is midazolam. Each 5 ml ampoule contains 5 mg of midazolam as hydrochloride.
• The other components are: sodium chloride, hydrochloric acid (for pH adjustment) and water for injectable preparations.

Appearance of the Product and Packaging Contents

Midazolam Normon 1 mg/ml is a sterile, transparent and colorless or practically colorless solution. It is presented as an injectable solution in 5 ml ampoules. Each package contains 10 or 50 ampoules.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

LABORATORIOS NORMON, S.A.

Ronda de Valdecarrizo, 6 - 28760 Tres Cantos - Madrid (SPAIN)

Date of Last Revision of this Prospectus:June 2023.

----------------------------------------------------------------------------------------------------------------------------

This information is intended only for healthcare professionals

For conscious sedation before a diagnostic or surgical intervention, midazolam will be administered intravenously. The dose must be individualized and adapted, and should not be administered in a rapid injection in a single bolus. The onset of sedation may vary individually depending on the patient's physical condition and the detailed circumstances of the posology. If necessary, subsequent doses may be administered according to individual needs. The medication starts to act approximately 2 minutes after injection. A maximum effect is achieved within 5 to 10 minutes.

Compatibility with infusion solutions:

The solution of Midazolam Normon 1 mg/ml injectable and infusion solution can be diluted with sodium chloride 0.9%, dextrose 5% and 10%, levulose 5%, Ringer's solution and Hartmann's solution in a mixture of 15 mg of midazolam per 100-1000 ml of solution. These solutions remain stable for 24 hours at room temperature or 3 days in the refrigerator at 2 to 8 °C. The solution of Midazolam Normon 1 mg/ml injectable and infusion solution cannot be diluted with Macrodex 6% in glucose or mixed with alkaline injections.

Adults:

The intravenous injection of midazolam should be administered slowly at a rate of approximately 1 mg in 30 seconds.

Children:

The use is not recommended for children under 6 months in conscious sedation and anesthesia, as there is hardly any data available for this population.

• Intravenous administration: the dose of midazolam should be adjusted slowly until the desired clinical effect is achieved. The initial dose of midazolam should be administered over 2 or 3 minutes. Wait 2 to 5 minutes more to accurately check the sedative effect before starting the procedure or repeating the dose. If more sedation is needed, the posology should be adjusted with small increments until the appropriate degree of sedation is achieved.
• Rectal administration: the total dose of midazolam usually varies between 0.3 and 0.5 mg/kg. The rectal administration of the ampoule solution is performed using a plastic applicator attached to the end of the syringe. If the volume to be administered is too small, water can be added up to a total volume of 10 ml. The total dose should be administered at once and repeated rectal administration should be avoided.
• Intramuscular administration: this route should only be used in exceptional cases. Rectal administration is preferred, as intramuscular injection is painful.

Treatment in case of overdose:

In most cases, it is only necessary to monitor vital functions. In the treatment of overdose, special attention should be paid to respiratory and cardiovascular functions in the intensive care unit (ICU). Flumazenil, a benzodiazepine antagonist, is indicated in case of severe poisoning accompanied by coma or respiratory depression. Caution should be exercised when using flumazenil in case of mixed pharmacological overdose and for patients with epilepsy already treated with benzodiazepines. Flumazenil should not be used for patients treated with tricyclic antidepressants or epileptogenic drugs, nor for patients with electrocardiogram abnormalities (prolongation of QRS or QT).

-