Leaflet: information for the user

Midazolam Normon 5 mg/ml injectable solution and for infusion EFG

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

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

Midazolam is indicated for:

For adults:

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

Premedication before anesthetic induction.

Anesthetic induction.

As a sedative component in combined anesthesia.

• Sedation in Intensive Care Units (ICU).

For children:

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

This medication should only be used when there are adequate resuscitation facilities available for each type of patient, as the intravenous administration of this medication can depress myocardial contractility (decrease in 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 medication (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 medication, if it is administered in:

• Adults over 60 years old.

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

• Patients with chronic respiratory insufficiency.

• Patients with chronic renal insufficiency.

• Patients with altered cardiac function.
• Patients with altered liver function.

• Patients with myasthenia gravis (severe muscle weakness).

These high-risk patients require lower doses and should be continuously monitored for early signs of vital function alterations.

• Patients with a history of alcohol or drug abuse.

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

Also, the following aspects should be taken into account while on treatment with this medication:

Tolerance:

Certain decrease in efficacy has been described when midazolam is used for prolonged sedation in intensive care units (ICUs).

Dependence:

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

Withdrawal symptoms:

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

Amnesia:

Midazolam causes anterograde amnesia (partial or total loss of memory of events that occurred immediately 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 ambulatory patients, for whom discharge is planned after the intervention. After receiving midazolam by parenteral route, patients may leave the hospital or clinic only if accompanied by another person.

Paradoxical reactions:

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

Children and adolescents

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

Other medications and Midazolam Normon

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

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

It is essential to inform your doctor if you are taking or have taken recently any of the following medications:

• Itraconazole, fluconazole, and ketoconazole (antifungal medications).
• Verapamil and diltiazem (calcium channel blockers).
• Erythromycin and clarithromycin (macrolide antibiotics).
• Cimetidine and ranitidine (ulcerative gastroduodenal medication).
• Saquinavir and other protease inhibitors (medications used in HIV (AIDS) treatment).
• Central Nervous System depressants (opioids, antipsychotics, and other benzodiazepines).
• Opioids, phenobarbital, and benzodiazepines. It is necessary to closely monitor an additional increase in respiratory depression when treating these medications with Midazolam.

Sedation should be taken into account when midazolam is combined with sedative medications.

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

Midazolam Normon with food, drinks, and alcohol

Alcohol can significantly potentiate the sedative effect of midazolam.It is essential to avoid alcohol consumption when administering midazolam.

Pregnancy, lactation, and fertility

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

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

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

Lactation

It is recommended that breastfeeding mothers suspend lactation for 24 hours after midazolam administration.

Driving and operating machinery

Midazolam is a medication that causes sleep. Do not drive or operate machinery if you feel drowsy or notice that your attention and reaction time are reduced. Pay special attention to the start of treatment or if the dose is increased.

The doctor will decide when these activities can be resumed.

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

Midazolam Normon contains sodium

This medication contains less than 23 mg of sodium (1 mmol) per 3 ml ampoule; this is essentially "sodium-free".

This medication contains 25.5 mg of sodium (main component of table salt/for cooking) in each 10 ml ampoule. This corresponds to 1.28% of the maximum recommended sodium intake for an adult.

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor again. Your doctor will inform you of the duration of your treatment with Midazolam Normon.

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

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

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, cardiopulmonary 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. Phone (91) 562 04 20.

Treatment in case of overdose:

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Side effects can occur at 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 available data).

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

Dermatological and appendage disorders: skin rash (redness of the skin), urticaria (allergy), itching, swelling of the face, lips, tongue, or throat that makes it difficult to swallow or breathe.

Central and peripheral nervous system and psychiatric disorders: prolonged somnolence and sedation, decreased alertness, confusion, euphoria, hallucinations, fatigue, headache, dizziness, ataxia (discoordination of movements), 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 reaction, aggression, paroxysmal excitement, and threats and insults, particularly in the case of children and the elderly.

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

The use ofmidazolam, even at therapeutic doses, may favor the development of physical dependence after prolonged intravenous administration; abrupt discontinuation of the drug may be accompanied by withdrawal symptoms, such as convulsions.

Gastrointestinal disorders: nausea, vomiting, hiccups, constipation, and dry mouth.

Cardiovascular and respiratory disorders: severe cardiovascular and respiratory adverse events: respiratory depression, apnea (pause in breathing), respiratory arrest, or cardiac arrest, hypotension, altered heart rate, vasodilatory effects, dyspnea (sensation of lack of air), and laryngospasm. Potentially fatal incidents are more likely in the case of adults over 60 years old and those patients with pre-existing respiratory insufficiency or cardiac function alteration, 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 seek medical attention immediately if you notice any of the following side effects. They may be potentially fatal and may require urgent medical treatment:

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

Site reactions: erythema (redness) and pain at the injection site, circulatory changes (thrombophlebitis and thrombosis).

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor, nurse, or pharmacist, even if it is a possible adverse reaction that does not appear in this prospectus.

You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: www.notificaRAM.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

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

Do not freeze. Additionally, a precipitate may form that dissolves upon agitation of the contents at room temperature.

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

Composition of Midazolam Normon 5 mg/ml injectable solution and for perfusion

• The active ingredient is midazolam. Each 3 ml ampoule contains 15 mg of midazolam as hydrochloride. Each 10 ml ampoule contains 50 mg of midazolam as hydrochloride.
• The other components are: sodium chloride, hydrochloric acid (for pH adjustment) and water for injection preparations.

Appearance of the product and contents of the package

Midazolam Normon 5 mg/ml is a sterile, transparent and colorless or almost colorless solution. It is presented as an injectable solution in 3 ml and 10 ml ampoules. Each package contains 5 ampoules of 3 ml, 10 ampoules of 10 ml or 50 ampoules of 3 ml or 10 ml.

Only some package sizes may be commercially marketed.

Holder of the marketing authorization and responsible for manufacturing

Laboratorios Normon, S.A.

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

Date of the last review of this leaflet:June 2023.

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

This information is intended solely for healthcare professionals

For conscious sedation before a diagnostic or surgical procedure, midazolam will be administered via IV. The dose must be individualized and adapted, and should not be administered in a single rapid injection. The onset of sedation may vary individually depending on the patient's physical condition and the specific circumstances of the posology. If necessary, subsequent doses may be administered in accordance with individual needs. The medication begins to act approximately 2 minutes after injection. An effect is obtained in 5 to 10 minutes.

Compatibility with perfusion solutions:

The Midazolam Normon 5 mg/ml injectable solution and for perfusion solution may 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 100-1,000 ml of solution. These solutions remain stable for 24 hours at room temperature or 3 days in a refrigerator at 2 to 8 °C. The Midazolam Normon 5 mg/ml injectable solution and for perfusion solution cannot be diluted with Macrodex 6% in glucose or mixed with alkaline injections.

Adults:

Midazolam IV injection 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 for conscious sedation and anesthesia, as there is little data available for this population.

• IV administration: the midazolam dose should be adjusted slowly to achieve the desired clinical effect. The initial midazolam dose should be administered over 2 or 3 minutes. Allow 2 to 5 minutes to accurately assess the sedative effect before initiating the procedure or repeating the dose. If more sedation is needed, continue adjusting the posology with small increments until the appropriate level of sedation is achieved.
• Rectal administration: the total midazolam dose usually varies between 0.3 and 0.5 mg/kg. 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 may be added to a total volume of 10 ml. The total dose should be administered at once and repeated rectal administration should be avoided.
• IM administration: This route should only be used in exceptional cases. Rectal administration is preferred, as IM injection is painful.

Treatment in case of overdose:

In most cases, only monitoring of vital functions is necessary. 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 cases of severe poisoning accompanied by coma or respiratory depression. Flumazenil should be used with caution in cases of mixed pharmacological overdose and in patients with epilepsy already treated with benzodiazepines. Flumazenil should not be used in patients treated with tricyclic antidepressants or epileptogenic drugs, or in patients with electrocardiogram abnormalities (prolongation of QRS or QT).