Midazolam Normon 1 mg/ml solution for injection and infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Midazolam Normon 1 mg/ml injectable and infusion solution EFG

Read the entire package 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, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult 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 adverse 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 of 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 anaesthesia induction.

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 anaesthesia induction.
• 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 in patients with severe respiratory insufficiency or acute respiratory depression.

Warnings and precautions

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

• Adults 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: close 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 reduction in efficacy has been reported when midazolam is used for prolonged sedation in intensive care units (ICU).

Dependence:

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

Withdrawal symptoms:

Prolonged treatment with midazolam in the ICU may lead to physical dependence. Therefore, abrupt discontinuation of treatment may be accompanied by 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, gradual dose reduction is recommended (see section 3).

Amnesia:

Midazolam causes anterograde amnesia (partial or complete loss of memory for events occurring shortly after recovery of consciousness; this effect is often 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 in outpatient settings where discharge is expected after the procedure. After receiving parenteral midazolam, patients may leave the hospital or clinic only if 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, rage reactions, aggressiveness, paroxysmal excitement (episodes of excitement), threats, and verbal abuse. 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 in children under 6 months of age is not recommended for conscious sedation or 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 to 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 ulcer).
• 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 taken into account when midazolam is combined with sedative medicines.

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

Taking 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. Its use for cesarean section is not recommended.

The risk to the fetus should be considered when midazolam is administered for any surgical procedure near the end of pregnancy.

Breastfeeding

Breastfeeding mothers are advised to discontinue breastfeeding for 24 hours after midazolam administration.

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 reduced. Pay special attention at the beginning of treatment or when 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 vial; hence, it is essentially “sodium-free”.

3. How to use Midazolam Normon

Follow exactly the administration instructions for this medicine as indicated 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 can 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, mental confusion, lethargy, muscle relaxation, or paradoxical excitation. More severe symptoms would include areflexia (absence of normal reflexes), hypotension, cardiorespiratory depression, apnea (respiratory pause), 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 the treatment of overdose, special attention must 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 the available data).

The following adverse reactions have been reported (very rarely) following administration of midazolam:

Skin and appendages disorders: skin rash (reddening of the skin), urticaria (allergy), 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 reported, 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 (pause in breathing), respiratory arrest or cardiac arrest, hypotension, changes in heart rate, vasodilatory effects, dyspnea (shortness of breath), and laryngospasm. Potentially life-threatening events 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 contact your doctor immediately if you experience any of the following side effects. They 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 have chest pain, which could be a sign of a potentially serious allergic reaction called 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 can also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: 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 additional information

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

• The active substance 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 injections.

Appearance of the product and contents of the container

Midazolam Normon 1 mg/ml is a sterile, clear, colourless or practically colourless solution. It is supplied as an injection solution in 5 ml ampoules. Each pack contains 10 or 50 ampoules.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

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

Date of the most recent revision of this summary: June 2023.

Detailed information on 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 packaging. You can also access this information at the following internet address: https://cima.aemps.es/cima/dochtml/p/63936/P_63936.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 medicine starts to act approximately 2 minutes after injection. Maximum effect is achieved within 5 to 10 minutes.

Compatibility with infusion solutions:

Midazolam Normon 1 mg/ml injection 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 for 3 days when refrigerated at 2–8 °C. Midazolam Normon 1 mg/ml injection 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 there is limited data available in this population.

• IV administration: midazolam dosage should be slowly titrated until the desired clinical effect is achieved. 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 proceeding with the procedure or repeating the dose. If further sedation is required, dosing should be gradually increased in small increments until the appropriate level of sedation is attained.
• 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 tip 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 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 intramuscular (IM) injection is painful.

Management in case of overdose:

In most cases, monitoring of vital functions is sufficient. In the management of overdose, special attention should be paid to respiratory and cardiovascular functions in an intensive care unit (ICU). Flumazenil, a benzodiazepine antagonist, is indicated in cases of severe intoxication associated with 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 must not be used in patients treated with tricyclic antidepressants or epileptogenic drugs, or in patients with electrocardiogram abnormalities (QRS or QT prolongation).