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

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

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

Read the entire 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.

  1. If you have any questions, ask your doctor, pharmacist or nurse.

• This medicine has been prescribed for you only. Do not pass it on to other people, even if they have the same symptoms as you, because it could harm them.

  • If you experience any adverse effects, talk to your doctor, pharmacist or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

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

The active substance in Midazolam Serraclinics is midazolam; it belongs to the group of benzodiazepines, drugs known as hypnotics (sleep-inducing agents) and sedatives (drugs that reduce nervous excitation).

Midazolam Serraclinics is indicated:

In adults for:

?Conscious Sedation before and during diagnostic or therapeutic procedures with or without local anesthesia.

?Anesthesia

• Premedication before anesthesia induction.
• Induction of anesthesia.
• As a sedative component in combined anesthesia.

?Sedation in Intensive Care Units (ICU).

In children for:

?Conscious Sedation before and during diagnostic or therapeutic procedures with or without local anesthesia.

?Anesthesia

• Premedication before anesthesia induction.

?Sedation in Intensive Care Units (ICU).

2. What you need to know before using Midazolam Serraclinics

This medicine must only be used when appropriate resuscitation equipment is available for each type of patient, as intravenous administration of Midazolam Serraclinics may depress myocardial contractility (reduced heart contractions) and cause apnea (cessation of breathing).

Do not use Midazolam Serraclinics

• If you are allergic to midazolam, benzodiazepines, or 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, pharmacist, or nurse before starting to use Midazolam Serraclinics.

• If administration is considered in:

• 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 overdose symptoms may occur.

• The following aspects should also be taken into account during treatment with this medicine:

• Tolerance

A certain reduction in efficacy has been reported when Midazolam Serraclinics is used for prolonged sedation in intensive care units (ICU).

• Dependence

When Midazolam Serraclinics 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 Serraclinics in the 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 how Midazolam Serraclinics will be administered to you).

• Amnesia

Midazolam Serraclinics causes anterograde amnesia (partial or complete loss of memory of events occurring shortly after regaining consciousness; this effect is often desirable before and during surgical interventions and diagnostic procedures). The duration of amnesia is directly related to the dose administered. Prolonged amnesia may pose problems in outpatient settings where early discharge is expected 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 Serraclinics, such as agitation, involuntary movements (tonic/clonic seizures and muscle tremor), hyperactivity, hostility, rage reaction, 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 is not recommended in children under 6 months of age for conscious sedation or anesthesia.

Other medicines and Midazolam Serraclinics

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

Certain medicines may interact with Midazolam Serraclinics; 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 ulcers)
• Saquinavir and other protease inhibitors (medicines used in the treatment of HIV infection (AIDS))
• CNS 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 Serraclinics.

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

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

Use of Midazolam Serraclinics with food, drinks, and alcohol

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

Pregnancy, breastfeeding, and fertility

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

Midazolam Serraclinics 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 Midazolam Serraclinics is administered for any surgical procedure near the end of pregnancy.

Breastfeeding mothers are advised to suspend breastfeeding for 24 hours after administration of Midazolam Serraclinics.

Driving and using machines

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

3. How to use Midazolam Serraclinics

Follow exactly the administration instructions for this medicine as indicated by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist again.

Your doctor will determine the duration of your treatment with Midazolam Serraclinics.

Dosage and methods of administration

Midazolam Serraclinics 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 Serraclinics can be administered as an intravenous bolus, intravenous infusion, intramuscular injection, or rectally.

If you have been given more Midazolam Serraclinics than you should have

Symptoms:

Symptoms of overdose include: drowsiness, 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 have been given more Midazolam Serraclinics than intended, 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 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 experiences 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 the administration of Midazolam Serraclinics:

Skin and subcutaneous tissue disorders: skin rash (reddening of the skin), urticaria (allergy), itching.

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

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

The use of Midazolam Serraclinics, even at therapeutic doses, may lead to 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 (respiratory pause), 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).

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

Seek immediate medical attention or call for an ambulance if the patient experiences any of the following adverse effects:

• Swelling of the face, lips, tongue, or throat causing difficulty swallowing or breathing.

Stop taking Midazolam Serraclinics and contact your doctor immediately if you notice 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 parts of the body. 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.

If any other reaction not described in this leaflet occurs, consult your doctor or pharmacist.

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor or pharmacist, even if these are possible adverse effects not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Midazolam Serraclinics

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

Do not use this medicine after the expiry date stated on the carton after EXP. The expiry date refers to the last day of the month indicated.

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

Do not store above 25°C.

Your doctor or pharmacist is responsible for the storage of midazolam. They are also responsible for the proper disposal of any unused medicine remaining after administration.

6. Contents of the pack and other information

• The active substance is midazolam. Each 1 ml ampoule contains 5 mg of midazolam, each 3 ml ampoule contains 15 mg of midazolam, each 10 ml ampoule contains 50 mg of midazolam, and each 20 ml vial contains 100 mg of midazolam.
• The other components (excipients) are: sodium chloride, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), and water for injections.

Nature of the product and contents of the container

Midazolam Serraclinics is presented as an injectable solution in ampoules or vials. The solution is transparent, colourless or slightly yellow. Each pack may contain:

• 10 or 50 ampoules of 1 ml (5 mg/1 ml)
• 5 or 50 ampoules of 3 ml (15 mg/3 ml)
• 10 or 50 ampoules of 10 ml (50 mg/10 ml)
• 10 or 50 vials of 20 ml (100 mg/20 ml)

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:

Laboratorios Serra Pamies, S.A.

Ctra. Castellvell, 24

43206 REUS (Tarragona)

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

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

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 individualised and adapted, and must not be administered as a rapid 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 begins to act approximately 2 minutes after injection. Maximum effect is achieved within 5 to 10 minutes.

Compatibility with infusion solutions

Midazolam Serraclinics ampoule solution may be diluted with 0.9% sodium chloride, 5% and 10% dextrose, 5% levulose, Ringer's solution, and Hartmann's solution, using a mixing ratio of 15 mg midazolam per 100–1000 ml of solution. These solutions remain stable for 24 hours at room temperature or for 3 days at 5°C. Midazolam Serraclinics ampoule solution must not be diluted with Macrodex 6% in dextrose or mixed with alkaline injections.

Adults

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 anaesthesia, as there is very 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 starting the procedure or repeating the dose. If further sedation is required, dosage should be gradually adjusted in small increments until the appropriate level of sedation is attained.

• Rectal administration: the total dose of midazolam usually 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 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.

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).