MIDAZOLAM SERRACLINICS 5 mg/ml INJECTABLE SOLUTION AND PERFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Midazolam Serraclinics 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, as you may need to read it again.
• 1. If you have any further questions, ask your doctor, pharmacist, or nurse.

• This medicine has been prescribed for you only, and you should 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, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of theleaflet

1. What is Midazolam Serraclinics and what is it used for
2. What you need to know before you use Midazolam Serraclinics
3. How to use Midazolam Serraclinics
4. Possible side effects
   1. Storage of Midazolam Serraclinics
   2. Packaging contents and further information

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

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

Midazolam Serraclinics 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 Serraclinics

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

Do not use Midazolam Serraclinics

• 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, pharmacist, or nurse before starting to use Midazolam Serraclinics.

• If administered in:

• Adults over 60 years of age.

• 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 vital function alterations.

• Patients with a history of alcohol or drug abuse.

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

• Also, the following aspects that may occur during treatment with this medicine should be taken into account:

• Tolerance

A certain decrease in efficacy has been described 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, it should be taken into account that it may produce physical dependence. The risk of dependence increases with the dose and duration of treatment.

• Withdrawal symptoms

During prolonged treatment with Midazolam Serraclinics in the ICU, physical dependence may occur. Therefore, abrupt interruption of treatment will be accompanied by withdrawal symptoms. The following symptoms may occur: headache, myalgia (muscle pain), anxiety, tension, restlessness, confusion, irritability, insomnia, mood changes, hallucinations, and convulsions. As the risk of withdrawal symptoms is higher after abrupt discontinuation of treatment, it is recommended to gradually decrease the doses (see how Midazolam Serraclinics will be administered to you).

• Amnesia

Midazolam Serraclinics 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 parenterally, patients may leave the hospital or office only if accompanied by another person.

• Paradoxical reactions

Paradoxical reactions have been described with Midazolam Serraclinics, such as agitation, involuntary movements (tonic/clonic movements and muscle tremors), hyperactivity, hostility, anger, aggression, paroxysmal excitement (excitement attacks), 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 children and the elderly.

Children and adolescents

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

Other medicines and Midazolam Serraclinics

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

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

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

• Itraconazole, Fluconazole, and Ketoconazole (medicines for the treatment of fungal infections)
• Verapamil and Diltiazem (calcium antagonist medicines)
• Erythromycin and Clarithromycin (macrolide antibiotics)
• Cimetidine and Ranitidine (medicine for the treatment of 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. It is necessary to monitor especially for an additional increase in respiratory depression in the case of treatment with these medicines together with Midazolam Serraclinics

Additional sedation should be taken into account when Midazolam Serraclinics is combined with sedative medicines.

The intravenous administration of Midazolam Serraclinics decreases the minimum alveolar concentration (MAC) of inhalation anesthetics required for general anesthesia.

Using Midazolam Serraclinics with food, drinks, and alcohol

Alcohol can significantly potentiate the sedative effect of Midazolam Serraclinics. You should avoid consuming alcohol when Midazolam Serraclinics 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.

Midazolam Serraclinics 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 Serraclinics for any surgical intervention near the end of pregnancy.

It is recommended that breastfeeding mothers discontinue breastfeeding until 24 hours after administration of Midazolam Serraclinics.

Driving and using machines

Midazolam Serraclinics 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.

3. How to use Midazolam Serraclinics

Follow exactly the administration instructions of this medicine indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Your doctor will indicate the duration of your treatment with Midazolam Serraclinics

Dosage and administration methods

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 concomitantly administered medicines.

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

If you have been administered more Midazolam Serraclinics 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 have been administered more Midazolam Serraclinics than you should, consult your doctor or pharmacist immediately.

In case of overdose or accidental ingestion, consult the Toxicology 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 Serraclinics:

Disorders of the skin and subcutaneous tissue: skin rash (redness of the skin), urticaria (allergy), itching.

Disorders of the central and peripheral nervous system and psychiatric disorders: drowsiness and prolonged sedation, 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 registered more frequently in infants and premature newborns.

The use of Midazolam Serraclinics, even in 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.

Disorders of the digestive system: nausea, vomiting, hiccups, constipation, and dry mouth.

Cardiorespiratory disorders: serious adverse cardiorespiratory events: respiratory depression, apnea (pause in breathing), respiratory arrest, or cardiac arrest, hypotension, alteration of heart rate, vasodilatory effects, dyspnea (feeling of lack of air), and laryngospasm.

Potentially life-threatening incidents are more likely in adults over 60 years of age 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).

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

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

• Swelling of the face, lips, tongue, or throat that makes it difficult to swallow or breathe.

Stop taking Midazolam Serraclinics and consult your doctor immediately if you notice any of the following side effects. They can be potentially life-threatening and may require urgent medical treatment:

• Anaphylactic shock (a potentially life-threatening 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 difficulty breathing, wheezing, or breathing problems, or pale skin, weak and rapid pulse, or a feeling of loss of consciousness. Additionally, you may experience chest pain, which can be a sign of a potentially serious allergic reaction called Kounis syndrome.

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

Reporting of side effects

If you experience any side effects, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can contribute to providing 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 expiration date stated on the carton after EXP. The expiration date is the last day of the month indicated.

Do not freeze. A precipitate may form that dissolves when the contents are shaken 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 the medicine that remains after administration.

6. Container Content and Additional Information

• The active ingredient 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 injectable preparations.

Appearance of the Product and Container Content

Midazolam Serraclinics is presented as an injectable solution in ampoules or vials. The solution is transparent, colorless, or slightly yellow. Each container 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 some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer:

Laboratorios Serra Pamies, S.A.

Ctra. Castellvell, 24

43206 REUS (Tarragona)

Date of the Last Revision of this Leaflet: August 2023.

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

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This information is intended only for healthcare professionals:

For conscious sedation before a diagnostic or surgical procedure, 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 according to the patient's physical condition and the detailed circumstances of the dosage. If necessary, subsequent doses can 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 Perfusion Solutions

The solution of Midazolam Serraclinics ampoules can be diluted with sodium chloride 0.9%, dextrose 5% and 10%, levulose 5%, Ringer's solution, and Hartmann's solution with a mixing ratio of 15 mg of midazolam per 100-1000 ml of solution. These solutions remain stable for 24 hours at room temperature or 3 days at 5°C. The solution of Midazolam Serraclinics ampoules cannot be diluted with Macrodex 6% in dextrose 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 must 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 dosage should be continued to be adjusted with small increments until the appropriate degree of sedation is achieved.

• Rectal administration: the total dose of midazolam usually ranges from 0.3 to 0.5 mg/kg. The rectal administration of the ampoule solution is carried out through 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).