Midazolam b. braun

Package leaflet: Information for the user

Midazolam B. Braun, 5 mg/mL, solution for injection / for infusion
Midazolamum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any further questions, please consult your doctor or pharmacist.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist immediately. See section 4.

Leaflet contents

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

1. What Midazolam B. Braun is and what it is used for

Midazolam B. Braun is a short-acting medicine used to induce sedation (a state of profound calmness, drowsiness, or sleep) and to reduce anxiety and muscle tension. Its active substance belongs to a group of substances known as benzodiazepines.

The medicine is used in adults:

• as general anaesthesia to induce or maintain unconsciousness in the patient.

The medicine is also used in adults and children:

• to induce muscle relaxation or drowsiness in intensive care units. This is known as "sedation";
• before and during medical procedures or surgical interventions. In this case, patients remain conscious but feel very calm and sleepy. This is known as "procedural sedation";
• to induce relaxation or drowsiness prior to administration of an anaesthetic agent.

2. Important information before using Midazolam B. Braun

When not to use Midazolam B. Braun:

• if the patient has hypersensitivity (allergy) to midazolam or any of the other ingredients of this medicine (listed in section 6),
• if the patient is allergic to benzodiazepines, such as diazepam or nitrazepam,
• if the patient has significant breathing problems and requires midazolam for light sedation.

Warnings and precautions
Before starting treatment with Midazolam B. Braun, discuss this with your doctor or pharmacist.
The patient will be closely monitored while receiving this medicine. The doctor will ensure that necessary equipment and medications for emergency treatment and resuscitation are available.
The doctor will exercise particular caution and may very carefully adjust the dose in the following cases:

• in patients over 60 years of age,
• in patients with chronic diseases such as breathing problems or kidney, liver, or heart disorders,
• in patients who have a condition causing them to be very weak, exhausted, or lacking energy,
• in patients with a disease called "myasthenia" (a neuromuscular disorder causing muscle weakness),
• in patients who experience pauses in breathing during sleep (sleep apnoea),
• in patients who have ever been dependent on alcohol,
• in patients who have ever been dependent on drugs or narcotics.

Long-term use of this medicine may lead to:

• development of tolerance to midazolam. The medicine will become less effective and will not produce the desired effect.
• dependence on the medicine and withdrawal symptoms (see "Stopping Midazolam B. Braun" in section 3).

Midazolam causes memory loss, which begins after administration. The duration depends on the dose received. If the patient is to be discharged from hospital or a procedure room after a surgical or diagnostic procedure, a caregiver should accompany the patient home.
Children
If this medicine is to be given to a child:

• If any of the above situations apply to the child, inform the doctor or nurse.
• This is especially important if the child has a heart condition or breathing problems.

Midazolam B. Braun and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including over-the-counter medicines and herbal medicines.
This is extremely important because Midazolam B. Braun may affect the action of other medicines. Similarly, some other medicines may affect the action of Midazolam B. Braun.
Tell your doctor if the patient is taking any of the following medicines, especially:

• anxiolytics (medicines used to treat anxiety, stress, and agitation),
• hypnotics (medicines used to treat insomnia),
• sedatives (medicines causing calmness or drowsiness),
• antidepressants (medicines used to treat depression),
• very strong painkillers,
• antihistamines (medicines used to treat allergies),
• azole antifungals (medicines used to treat fungal infections), such as ketoconazole, voriconazole, fluconazole, itraconazole, or posaconazole,
• macrolide antibiotics (medicines used to treat bacterial infections), such as erythromycin, clarithromycin, telithromycin, or roxithromycin,
• calcium channel blockers (medicines used to treat high blood pressure), such as diltiazem or verapamil,
• protease inhibitors (medicines used to treat HIV or hepatitis C virus infection), such as boceprevir, saquinavir, simeprevir, or telaprevir,
• tyrosine kinase inhibitors (medicines used to treat certain cancers), such as idelalisib, imatinib, or lapatinib,
• NK1 receptor antagonists (medicines used to treat nausea and vomiting), such as aprepitant, netupitant, or casopitant,
• atorvastatin (a medicine used to treat high cholesterol levels),
• rifampicin (a medicine used to treat infections caused by mycobacteria, such as tuberculosis),
• ticagrelor (a medicine used to prevent heart attack),
• everolimus (a medicine used in transplantation and treatment of certain cancers),
• carbamazepine or phenytoin (medicines used to treat epilepsy),
• cyclosporine (a medicine used in transplantation),
• propiverine (a medicine used to treat overactive bladder syndrome),
• mitotane or enzalutamide (medicines used to treat certain cancers),
• clobazam (a medicine used to treat epilepsy or anxiety),
• efavirenz (a medicine used to treat HIV infection),
• vemurafenib (a medicine used to treat melanoma),
• herbal medicines: St. John's wort, quercetin, Ginkgo biloba, or Panax ginseng,
• valproic acid (a medicine used to treat epilepsy).

Midazolam B. Braun and alcohol
After receiving midazolam, alcoholic beverages must not be consumed, as alcohol intensifies the effects of midazolam in an uncontrolled manner. This may lead to severe adverse effects affecting the respiratory system, heart function, and circulatory system.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
If the patient is pregnant, midazolam will be administered only if the doctor considers it absolutely necessary in the context of treatment.
If the patient is breastfeeding, she should stop breastfeeding for 24 hours after administration of midazolam.
This is because midazolam may pass into human milk.

Driving and operating machinery
The patient should not drive or operate machinery until the effects of midazolam have completely worn off. The doctor will inform when it is safe to resume these activities.
The medicine may cause drowsiness, forgetfulness, or affect concentration and coordination.
The patient should ensure that another person accompanies them on their way home after discharge.

Midazolam B. Braun contains sodium
This medicine contains 2.19 mg of sodium (the main component of table salt) per 1 mL ampoule. This corresponds to 0.11% of the maximum recommended daily dietary sodium intake for adults.
This medicine contains 21.94 mg of sodium (the main component of table salt) per 10 mL ampoule. This corresponds to 1.01% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Midazolam B. Braun

This medicine will be administered to the patient by a doctor or nurse. It will be given in a place equipped with equipment for monitoring the patient's condition and treating any adverse reactions that may occur. This may be a hospital or a surgical clinic. In particular, the patient's breathing, heart function, and circulatory function will be monitored.
This medicine is not recommended for use in children and infants under 6 months of age. However, in exceptional circumstances occurring in intensive care units, administration in children and infants under 6 months of age may take place if the doctor considers it necessary.
Midazolam B. Braun is administered by syringe (as an injection) into a vein (intravenously) or into a muscle (intramuscularly). It may also be given diluted in a large volume of fluid through a catheter placed in a vein (as an infusion). Rectal administration using a special applicator may also be used if injection or infusion is not possible.
Dosing:
The doctor will determine the correct dose for the patient or child, according to the treatment the patient or child is to receive, and based on the patient's or child's health status.
Administration of a higher than recommended dose of Midazolam B. Braun
This medicine is administered to the patient by a doctor. If the patient accidentally receives too high a dose of midazolam, the patient may experience the following symptoms:

• drowsiness and lack of proper muscle control (coordination) and reflexes,
• speech disturbances and unusual eye movements,
• low blood pressure. In this case, the patient may feel lightheadedness or dizziness,
• slower breathing or breathing cessation, slower heart rate or cardiac arrest, and loss of consciousness (coma).

Treatment of overdose is primarily based on monitoring vital functions (heart, circulatory system, and respiration). The patient will receive appropriate treatment if necessary.
In case of acute poisoning, the patient may be given an antidote to counteract the effects of midazolam.
Discontinuation of Midazolam B. Braun treatment
If the patient suddenly stops treatment after prolonged use, withdrawal symptoms may occur, such as:

• headache,
• diarrhea,
• muscle pain,
• feelings of anxiety, tension, restlessness, confusion, or irritability (agitation),
• sleep disturbances,
• mood changes,
• hallucinations (seeing and possibly hearing things that are not really there),
• seizures (convulsions),
• depersonalization,
• numbness and tingling in the limbs,
• hypersensitivity to light, noise, and physical contact.

Towards the end of midazolam treatment, the doctor will gradually reduce the dose to prevent the occurrence of the above effects.
If there are any further doubts regarding the use of this medicine, consult a doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The following adverse effects have been reported (with unknown frequency: frequency cannot be
determined from available data).
The following adverse effects may be serious. If any of the following adverse effects occur,
inform your doctor immediately. The doctor will discontinue the medicine:

• Anaphylactic shock (a life-threatening allergic reaction). Symptoms include: rash, itching or lumpy rash (urticaria), and swelling of the face, lips, tongue or other parts of the body (angioedema). There may also be shortness of breath, wheezing or difficulty breathing (bronchospasm), or pale skin, weak and rapid pulse, or feeling faint. Additionally, chest pain may occur, which could be a symptom of a serious allergic reaction called Kounis syndrome.
• Myocardial infarction (cardiac arrest). Symptoms include: chest pain which may radiate to the neck and arms and along the left arm, breathing problems or complications (sometimes leading to respiratory arrest).
• Choking and sudden airway obstruction (laryngospasm).

Life-threatening adverse effects occur more frequently in adults over 60 years of age and in
patients with breathing difficulties or heart conditions, particularly if the injection is administered too quickly or if the dose is too high.
Other adverse effects:
Immune system disorders:

• General allergic reactions (skin reactions, circulatory and vascular reactions)

Effects on behaviour:

• Agitation,
• Motor restlessness,
• Irritability,
• Nervousness, anxiety,
• Hostility, anger or aggression,
• Episodes of excitement (paroxysmal agitation),
• Excessive activity,
• Offensive behaviour,
• Changes in libido,
• Inappropriate behaviour and other adverse behavioural effects.

Muscle problems:

• Muscle cramps or muscle tremors (muscle tremors which the patient cannot control).

Psychiatric and nervous system problems:

• Confusion, disorientation,
• Psychoses (loss of contact with reality),
• Emotional and mood disturbances,
• Hallucinations (seeing and possibly hearing things that are not really there),
• Drowsiness and prolonged sedation,
• Nightmares, unusual dreams,
• Reduced level of consciousness,
• Headache,
• Dizziness,
• Difficulty with muscle coordination,
• Seizures (convulsions), more frequently in premature infants and newborns,
• Temporary memory loss. The duration depends on the dose of midazolam administered. It may occur after treatment has ended. In isolated cases, it has persisted for a prolonged period.
• Drug dependence, drug misuse,
• Withdrawal symptoms, sometimes including seizures (convulsions).

Heart and circulatory system problems:

• Low blood pressure,
• Slow heart rate,
• Vasodilation.

Breathing problems:

• Slow breathing (respiratory depression),
• Shortness of breath (dyspnea),
• Cessation of breathing (apnea, respiratory arrest),
• Hiccups.

Gastrointestinal, intestinal and oral problems:

• Nausea,
• Vomiting,
• Constipation,
• Dry mouth.

Skin problems:

• Rash,
• Urticaria (lumpy rash),
• Itching.

Effects at the site of administration:

• Redness,
• Skin swelling,
• Blood clots or pain.

General:

• Fatigue (weakness).

Injuries, poisonings and procedural complications:

• Falls and bone fractures. This risk is higher in patients taking other sedative medicines (including alcohol) and in elderly patients.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, tell your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C,
02-222 Warsaw,
tel.: +48 22 49-21-301,
fax: +48 22 49-21-309,
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Midazolam B. Braun

The physician or pharmacist is responsible for storage of this medicinal product. They are also responsible for the proper disposal of any unused midazolam.

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

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

Do not store above 25°C.

Chemical and physical in-use stability has been demonstrated for 24 hours at room temperature and for 3 days at 5°C.

From a microbiological point of view, the diluted medicinal product should be used immediately after preparation. If not used immediately, the user is responsible for the storage duration and conditions, which should generally not exceed 24 hours between 2 and 8°C, unless the dilution was carried out under controlled and validated aseptic conditions.

Store containers in the outer packaging to protect from light.

6. Contents of the package and other information

What Midazolam B. Braun contains

• The active substance is midazolam (in the form of midazolam hydrochloride). Each mL of Midazolam B. Braun 5 mg/mL contains 5 milligrams of midazolam.
  • One 1 mL ampoule contains 5 milligrams of midazolam.
  • One 10 mL ampoule contains 50 milligrams of midazolam.
• The other ingredients are: sodium chloride, hydrochloric acid 10%, and water for injections.

What Midazolam B. Braun looks like and contents of the pack
Midazolam B. Braun is a clear, colourless aqueous solution.
Midazolam B. Braun 5 mg/mL is available in:

• 1 mL ampoules made of colourless glass in cardboard boxes containing 10 ampoules,
• 10 mL ampoules made of colourless glass in cardboard boxes containing 5 or 10 ampoules,
• 10 mL transparent ampoules made of LDPE in cardboard boxes containing 4, 10 or 20 ampoules.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
B. Braun Melsungen AG
Carl-Braun-Straße 1
34212 Melsungen
Germany
Postal address:
34209 Melsungen, Germany
Tel: +49-5661-71-0
Fax: +49-5661-71-4567

Manufacturer
B. Braun Melsungen AG
Carl-Braun-Straße 1
34212 Melsungen
Germany

This medicinal product is authorised in the European Economic Area countries under the following names:
Belgium Midazolam B. Braun 5 mg/mL
Cyprus Midazolam B. Braun 5 mg/mL
Denmark Midazolam B. Braun 5 mg/mL
Estonia Midazolam B. Braun 5 mg/mL
France Midazolam B. Braun 5 mg/mL
Germany Midazolam B. Braun 5 mg/mL
Greece Midazolam B. Braun 5 mg/mL
Italy Midazolam B. Braun 5 mg/mL
Latvia Midazolam B. Braun 5 mg/mL
Lithuania Midazolam B. Braun 5 mg/mL
Luxembourg Midazolam B. Braun 5 mg/mL
Malta Midazolam B. Braun 5 mg/mL
Norway Midazolam B. Braun 5 mg/mL
Poland Midazolam B. Braun
Slovenia Midazolam B. Braun 5 mg/mL raztopina za injiciranje/infundiranje
Spain Midazolam B. Braun 5 mg/mL

Information intended exclusively for healthcare professionals:

Warnings
Paradoxical reactions
Paradoxical reactions have been reported following administration of midazolam, such as hyper-
kinetic anxiety, excitation, irritability, involuntary movements (including tonic-clonic seizures and
muscle tremor), excessive activity, hostility, hallucinations, rage, aggression, anxiety, nightmares,
illusions, psychoses, inappropriate behavior and other behavioral adverse effects, paroxysmal agi-
tation and acts of violence. Such reactions may occur after administration of high doses and (or)
rapid injection. These reactions have most frequently been observed in children and elderly patients.
If such reactions occur, discontinuation of the medicinal product should be considered.
Sleep apnoea
Midazolam should be used with particular caution in patients with sleep apnoea syndrome and their
condition should be monitored regularly.

Handling
The medicinal product should be used immediately after opening.
Shelf-life after dilution according to instructions:
Chemical and physical in-use stability has been demonstrated for 24 hours at room temperature
and for 3 days at 5°C.
From a microbiological point of view, the diluted medicinal product should be used immediately
after preparation. If not used immediately, the user is responsible for the storage duration and con-
ditions, which generally should not exceed 24 hours at 2–8°C, unless dilution was carried out under
controlled and validated aseptic conditions.
The product is supplied in single-dose containers. Any unused portions from opened containers should
be discarded immediately.
Use only if the solution is clear and colourless, and the container and closure are undamaged.
Instructions for dilution, pharmaceutical incompatibilities, and detailed prescribing information are
provided in the Summary of Product Characteristics.