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

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Midazolam Normon 5 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, talk to your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

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

The active substance in Midazolam Normon is midazolam. It belongs to the group of benzodiazepines, medicines known as hypnotics (sleep-inducing agents) and sedatives (medicines that reduce nervous excitement).

Midazolam is indicated:

In adults for:

• Conscious sedation before and during diagnostic or therapeutic procedures with or without local anaesthesia.
• Anaesthesia:

Premedication before induction of anaesthesia.

Induction of anaesthesia.

As a sedative component in combined anaesthesia.

• Sedation in Intensive Care Units (ICU).

In children for:

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

2. What you need to know before using Midazolam Normon

This medicine should only be used when appropriate resuscitation equipment is available for each type of patient, as intravenous administration of this medicine may depress myocardial contractility (reduced heart contractions) and cause apnea (respiratory pause).

Do not use Midazolam Normon

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

Warnings and precautions

Consult your doctor or nurse before using this medicine if it is to be administered to:

• Elderly patients over 60 years of age.

• Pediatric patients, especially those with cardiovascular instability.

• Patients with chronic diseases or who are debilitated, such as:

• Patients with chronic respiratory insufficiency.

• Patients with chronic renal insufficiency.

• Patients with impaired cardiac function.

• Patients with impaired hepatic function.

• Patients with myasthenia gravis (severe muscle weakness).

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

• Patients with a history of alcohol or drug abuse.

• Patients receiving premedication: careful observation of the patient after administration is mandatory, as interindividual sensitivity varies and symptoms of overdose may occur.

The following aspects should also be considered during treatment with this medicine:

Tolerance:

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

Dependence:

When midazolam is used for prolonged sedation in ICU, physical dependence may occur. The risk of dependence increases with dose and duration of treatment.

Withdrawal symptoms:

Prolonged treatment with midazolam in ICU may lead to physical dependence. Therefore, abrupt discontinuation of treatment may result in withdrawal symptoms. The following symptoms may occur: headache, myalgia (muscle pain), anxiety, tension, restlessness, confusion, irritability, rebound insomnia, mood disturbances, hallucinations, and seizures. Since the risk of withdrawal symptoms is higher after abrupt discontinuation, it is recommended to gradually reduce the dose (see section 3).

Amnesia:

Midazolam causes anterograde amnesia (partial or total loss of memory for events occurring shortly after regaining consciousness; this effect is often highly desirable in situations such as before and during surgical interventions and diagnostic procedures). The duration of amnesia is directly related to the administered dose. Prolonged amnesia may pose problems for outpatient patients expected to be discharged after the procedure. After receiving midazolam by parenteral route, patients should only leave the hospital or clinic accompanied by another person.

Paradoxical reactions:

Paradoxical reactions have been reported with midazolam, such as agitation, involuntary movements (tonic-clonic seizures and muscle tremor), hyperactivity, hostility, anger reactions, paroxysmal excitement (episodes of excitement), threats, and insults. These reactions may occur with high doses or when the injection is administered rapidly. Such reactions are most frequently observed in children and elderly patients.

Children and adolescents

Use of midazolam is not recommended in children under 6 months of age for conscious sedation and anesthesia.

Other medicines and Midazolam Normon

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines.

Certain medicines may interact with midazolam; in such cases, it may be necessary to adjust the dose or discontinue treatment with one of the medicines.

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 (medicines used to treat fungal infections).
• Verapamil and diltiazem (calcium channel antagonists).
• Erythromycin and clarithromycin (macrolide antibiotics).
• Cimetidine and ranitidine (medicines used to treat gastroduodenal ulcers).
• Saquinavir and other protease inhibitors (medicines used in the treatment of HIV infection (AIDS)).
• Central Nervous System depressants (opioids, antipsychotics, and other benzodiazepines).
• Opioids, phenobarbital, and benzodiazepines. Additional respiratory depression should be especially monitored when these medicines are used concomitantly with Midazolam.

Additional sedation should be considered when midazolam is combined with sedative medicines.

Intravenous administration of midazolam reduces the minimum alveolar concentration (MAC) of inhaled anesthetics required for general anesthesia.

Use of Midazolam Normon with food, drinks, and alcohol

Alcohol may considerably enhance the sedative effect of midazolam. Consumption of alcohol should be avoided when midazolam is administered.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

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 considered when administering midazolam for any surgical procedure near the end of pregnancy.

Breastfeeding

Breastfeeding women are advised to suspend breastfeeding for 24 hours after administration of midazolam.

Driving and using machines

Midazolam is a medicine that causes drowsiness. Do not drive or operate machinery if you feel sleepy or if your attention and reaction ability are impaired. Pay special attention at the beginning of treatment or when the dose is increased.

Your 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 medicine contains less than 23 mg of sodium (1 mmol) per 3 ml vial; this is essentially “sodium-free”.

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

3. How to use Midazolam Normon

Follow exactly the instructions for administration of this medicine as given by your doctor. If in doubt, consult your doctor again. Your doctor will determine 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 concomitant medications.

Midazolam Normon may be administered as an intravenous bolus, intravenous infusion, intramuscular injection, or rectally.

If you use more Midazolam Normon than you should

Symptoms:

Symptoms of overdose include: drowsiness, confusion, lethargy, muscle relaxation, or paradoxical excitation. More severe symptoms would include areflexia (absence of normal reflexes), hypotension, cardiopulmonary depression, apnea (breathing pauses), and coma.

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

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

Treatment in case of overdose:

In most cases, monitoring vital functions is sufficient. In treating overdose, special attention should be paid to respiratory and cardiovascular functions in an intensive care unit (ICU).

4. Possible adverse effects

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

Adverse effects may occur with certain frequencies, defined as follows:

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 reported (very rarely) with administration of midazolam:

Skin and appendages disorders: skin rash (reddening of the skin), urticaria (allergic reaction), itching, swelling of the face, lips, tongue, or throat causing difficulty in swallowing or breathing.

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

Paradoxical reactions have been described, such as agitation, involuntary movements (tonic/clonic movements and muscle tremor), hyperactivity, hostility, anger reaction, aggressiveness, paroxysmal excitement, threats, and verbal abuse, particularly in children and elderly patients.

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

The use of midazolam, even at therapeutic doses, may promote the development of physical dependence following prolonged intravenous administration; abrupt discontinuation of the drug may be accompanied by withdrawal symptoms such as seizures.

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

Cardiorespiratory disorders: serious cardiorespiratory adverse events: respiratory depression, apnea (cessation of breathing), respiratory arrest or cardiac arrest, hypotension, changes in heart rate, vasodilatory effects, dyspnea (shortness of breath), and laryngospasm. Potentially life-threatening incidents are more likely in patients over 60 years of age and in those with pre-existing respiratory insufficiency or impaired cardiac function, particularly when the injection is administered too rapidly or when a high dose is given.

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

Stop taking Midazolam Normon and seek immediate medical attention if you experience any of the following side effects. These may be potentially life-threatening and may require urgent medical treatment:

• Anaphylactic shock (a potentially life-threatening allergic reaction). Signs may include sudden rash, itching or lumpy rash (urticaria), and swelling of the face, lips, tongue, or other body parts. You may also experience shortness of breath, wheezing or difficulty breathing, or pale skin, weak and rapid pulse, or feeling faint. Additionally, you may experience chest pain, which could be a sign of a potentially serious allergic reaction known as Kounis syndrome.

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

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, nurse, or pharmacist, even if it is a possible adverse effect not listed in this leaflet.

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

5. Storage of Midazolam Normon

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

Do not freeze. A precipitate may form, which dissolves upon shaking the contents at room temperature.

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date is the last day of the month indicated.

6. Package contents and other information

Composition of Midazolam Normon 5 mg/ml injectable and infusion solution

• The active substance 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 injectable preparations.

Appearance of the product and contents of the package

Midazolam Normon 5 mg/ml is a sterile, transparent, colourless or practically colourless solution. It is supplied as an injectable solution in 3 ml and 10 ml ampoules. Each pack contains either 5 ampoules of 3 ml, 10 ampoules of 10 ml, or 50 ampoules of either 3 ml or 10 ml.

Only certain pack sizes may be commercially available.

Marketing Authorisation Holder and Manufacturer

LABORATORIOS NORMON, S.A.
Ronda de Valdecarrizo, 6 - 28760 Tres Cantos - Madrid (SPAIN)

Date of the most recent review of this leaflet: June 2023

Detailed information about this medicine is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/

You can access detailed information about this medicine by scanning with your mobile phone (smartphone) the QR code included in the package leaflet and outer packaging. You can also access this information at the following internet address: https://cima.aemps.es/cima/dochtml/p/65796/P_65796.html

This information is intended for healthcare professionals only

For conscious sedation prior to a diagnostic or surgical procedure, midazolam should be administered intravenously (IV). The dose must be individualized and adjusted accordingly, and must not be administered as a rapid, single bolus injection. The onset of sedation may vary individually depending on the patient's physical condition and the specific circumstances of dosing. If necessary, additional doses may be administered according to individual needs. The drug begins to act approximately 2 minutes after injection. Maximum effect is achieved within 5 to 10 minutes.

Compatibility with infusion solutions:

Midazolam Normon 5 mg/ml injectable and infusion solution may be diluted with 0.9% sodium chloride, 5% and 10% dextrose, 5% levulose, Ringer's solution, and Hartmann's solution, to a mixture of 15 mg midazolam per 100–1,000 ml of solution. These solutions remain stable for 24 hours at room temperature or 3 days when refrigerated at 2–8°C. Midazolam Normon 5 mg/ml injectable and infusion solution must not be diluted with Macrodex 6% in glucose or mixed with alkaline injections.

Adults:

Intravenous (IV) injection of midazolam should be administered slowly at a rate of approximately 1 mg every 30 seconds.

Children:

Use in children under 6 months of age is not recommended for conscious sedation or anesthesia, as very limited data are available in this population.

• IV administration: midazolam dosage should be slowly titrated to achieve the desired clinical effect. The initial dose of midazolam should be administered over 2 to 3 minutes. An additional 2 to 5 minutes should be allowed to accurately assess the sedative effect before initiating the procedure or repeating the dose. If deeper sedation is required, dosage should be further adjusted in small increments until the appropriate level of sedation is achieved.
• Rectal administration: the total dose of midazolam typically ranges 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 a syringe. If the volume to be administered is too small, water may be added to achieve a total volume of 10 ml. The total dose should be administered 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.

Management in case of overdose:

In most cases, monitoring vital functions is sufficient. 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 intoxication accompanied by coma or respiratory depression. Caution must be exercised when using flumazenil in cases of mixed drug overdose and in patients with epilepsy already treated with benzodiazepines. Flumazenil should not be used in patients treated with tricyclic antidepressants or epileptogenic drugs, nor in patients with electrocardiogram abnormalities (QRS or QT prolongation).