MIDAZOLAM B. BRAUN 1 mg/ml INJECTABLE SOLUTION AND PERFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Midazolam B. Braun 1 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 further questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What Midazolam B. Braun is and what it is used for
2. What you need to know before you use Midazolam B. Braun
3. How to use Midazolam B. Braun
4. Possible side effects
5. Storage of 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 very relaxed state of calmness, drowsiness or sleep) and to relieve anxiety and muscle tension. Its active substance, midazolam, belongs to a group of substances called benzodiazepines.

This medicine is used in adults:

• as general anesthesia to induce sleep in the patient or to keep them asleep,

This medicine is also used in adults and children:

• to induce a feeling of relaxation or drowsiness in intensive care. This is known as "sedation".

• before and during a medical procedure or surgical intervention. In this case, patients remain awake but feel very calm and drowsy. This is known as "conscious sedation".

• to induce a feeling of relaxation or drowsiness before administering an anesthetic.

2. What you need to know before you use Midazolam B. Braun

Do not use Midazolam B. Braun:

• if you are hypersensitive (allergic) to midazolam or any of the other components of this medicine (listed in section 6).
• if you are allergic to benzodiazepines, such as diazepam and nitrazepam.
• if you have severe respiratory problems and need midazolam for conscious sedation.

Warnings and precautions

Talk to your doctor or pharmacist before you start using Midazolam B. Braun.

You will be closely monitored while you receive the medicine. Your doctor will also make sure that the necessary equipment and medicines are available for emergency treatment and resuscitation.

Your doctor will take special precautions and may adjust the dose with special care if:

• you are over 60 years old,
• you have a chronic disease, such as respiratory, renal, hepatic or cardiac problems,
• you have a disease that makes you feel weak, depressed and lacking energy
• you have a disorder called myasthenia gravis (a neuromuscular disease that causes muscle weakness),
• your breathing stops during sleep (sleep apnea),
• you have had alcohol addiction in the past,
• you have had substance addiction in the past.

If you receive this medicine for a long time, it is possible that:

• you will become tolerant to midazolam. The medicine will lose its effectiveness and will not work as well for you.
• you will become dependent on this medicine and suffer from withdrawal symptoms (see "If you stop using Midazolam B. Braun" in section 3).

Midazolam will cause memory loss that will start with administration. The duration will depend on the dose you receive. If you are discharged from the hospital or clinic after a surgical or diagnostic procedure, make sure someone accompanies you home.

Children

If your child is going to receive this medicine:

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

Other medicines and Midazolam B. Braun

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription and herbal products.

This is especially important because Midazolam B. Braun can affect the effect of other medicines. Similarly, other medicines can affect the effect of Midazolam B. Braun

In particular, tell your doctor if you are taking any of the following medicines:

• tranquilizers (medicines used to treat anxiety, stress and nervousness)
• hypnotics (sleeping medicines)
• sedatives (medicines to feel calm or drowsy)
• antidepressants (medicines used to treat depression)
• very powerful painkillers
• antihistamines (medicines to treat allergies)
• azolic antifungals (medicines to treat fungal infections) such as ketoconazole, voriconazole, fluconazole, itraconazole or posaconazole
• macrolide antibiotics (medicines to treat bacterial infections) such as erythromycin, clarithromycin, telithromycin or roxithromycin
• calcium channel blockers (medicines to treat high blood pressure) such as diltiazem or verapamil
• protease inhibitors (medicines to treat HIV or hepatitis C infection) such as boceprevir, saquinavir, simeprevir or telaprevir
• tyrosine kinase inhibitors (medicines to treat certain cancers) such as idelalisib, imatinib or lapatinib
• NK1 receptor antagonists (medicines to treat nausea and vomiting) such as aprepitant, netupitant or casoprepitant
• atorvastatin (medicine to treat high cholesterol levels)
• rifampicin (medicine to treat mycobacterial infections such as tuberculosis)
• ticagrelor (medicine to prevent heart attack)
• everolimus (medicine used in transplants and to treat certain cancers)
• carbamazepine or phenytoin (medicines to treat epilepsy)
• cyclosporin (medicine used in transplants)
• propiverine (medicine to treat an overactive bladder)
• mitotane or enzalutamide (medicines to treat certain cancers)
• clobazam (medicine to treat epilepsy or anxiety)
• efavirenz (medicine to treat HIV infection)
• vemurafenib (medicine to treat melanoma)
• St. John's Wort, quercetin, Ginkgo bilobaor Panax ginseng(herbal products)
• valproic acid (medicine to treat epilepsy)

Using Midazolam B. Braun with alcohol

Do not drink alcoholic beverages if you are receiving midazolam, as alcohol will increase the effect of midazolam in an uncontrolled way. This could cause serious adverse reactions in breathing, heart function and circulation.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

If you are pregnant, you will receive midazolam only if your doctor considers it absolutely necessary in the context of your treatment.

If you are breast-feeding, stop breast-feeding for 24 hours after administration of midazolam.

Driving and using machines

Do not drive or use any tools or machines until you have fully recovered from midazolam. Your doctor will tell you when you can resume this activity again.

This medicine may cause drowsiness and memory loss or affect your concentration and coordination. Make sure someone accompanies you home when you are discharged.

Midazolam B. Braun contains sodium

This medicine contains 17.63 mg of sodium (main component of table salt/cooking salt) in each 5 ml ampoule. This is equivalent to 0.88% of the maximum recommended daily intake of sodium for an adult.

This medicine contains 176.33 mg of sodium (main component of table salt/cooking salt) in each 50 ml vial. This is equivalent to 8.81% of the maximum recommended daily intake of sodium for an adult.

This medicine contains 352.65 mg of sodium (main component of table salt/cooking salt) in each 100 ml vial. This is equivalent to 17.63% of the maximum recommended daily intake of sodium for an adult.

3. How to use Midazolam B. Braun

This medicine will be administered to you by a doctor or nurse. It will be used in a place equipped to monitor you and to treat any adverse effects that may occur. This place may be a hospital or an outpatient surgery clinic. In particular, your breathing, heart function and circulation will be monitored.

It is not recommended to use this medicine in newborns or in children under 6 months of age. However, in intensive care situations, it may be used in newborns and children under 6 months of age if the doctor considers it necessary.

Midazolam will be administered with a syringe (as an injection) into a vein (intravenously) or into a muscle (intramuscularly). It can also be administered diluted in a larger amount of liquid, through a cannula placed in a vein (by infusion). Rectal administration with a special applicator is also possible if injection or infusion is not feasible.

Dosage:

Your doctor will determine the correct dose for you or your child, depending on the treatment you or your child will receive and depending on your or your child's condition.

If you use more Midazolam B. Braun than you should

This medicine will be administered to you by a doctor. If you accidentally receive too much midazolam, you may feel:

• drowsiness and loss of normal muscle control (coordination) and reflexes.
• speech disorders and unusual eye movements
• low blood pressure. You may feel dizzy or lightheaded.
• slow or stopped breathing or heart rate and loss of consciousness (coma)

Treatment of overdose consists mainly of monitoring your vital functions (heart function, circulation and breathing). You will receive adequate support if necessary.

In cases of severe poisoning, you may receive a special antidote to counteract the effect of midazolam.

If you stop using Midazolam B. Braun

If you stop treatment suddenly after prolonged use, you may suffer from withdrawal symptoms such as:

• headaches,
• diarrhea,

• muscle pain,
• feeling of anxiety, tension, restlessness, confusion or bad mood (irritability),
• sleep disorders,
• mood changes,
• hallucinations (seeing and possibly hearing things that are not there),
• seizures,
• depersonalization,
• numbness and tingling in the limbs,
• hypersensitivity to light, noise and physical contact,

Your doctor will gradually reduce the dose towards the end of treatment with midazolam to avoid these effects.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following side effects have been reported (frequency not known: cannot be estimated from the available data).

The following side effects may be serious. If you experience any of the following side effects, tell your doctor immediately, who will stop administering this medicine:

• Anaphylactic shock (a potentially life-threatening allergic reaction). The signs may be sudden onset of skin rash, itching or hives and swelling of the face, lips, tongue or other parts of the body (angioedema). You may also experience shortness of breath, wheezing or difficulty breathing (bronchospasm), or pale skin, weak and rapid pulse, or feeling of loss of consciousness. Additionally, you may experience chest pain, which can be a sign of a serious allergic reaction called Kounis syndrome.
• Heart attack (cardiac arrest). The signs may be chest pain that may spread to the neck and shoulders and down the left arm, and respiratory problems or complications (which can sometimes cause respiratory arrest).
• Sudden asphyxia and airway obstruction (laryngospasm).

Life-threatening side effects are more likely to occur in adults over 60 years of age and in those who already have breathing difficulties or heart problems, especially if the injection is given too quickly or with a high dose.

Other side effects:

Immune system disorders:

• general allergic reactions (skin, heart and blood reactions)

Behavioral effects:

• agitation

• restlessness
• irritability
• nervousness, anxiety
• hostility, anger or aggression
• paroxysmal excitement (excitement)
• hyperactivity
• offensive behavior
• changes in libido
• inadequate behavior and other behavioral side effects

Muscle problems:

• muscle spasms and tremors (involuntary muscle contractions)

Mental and nervous system disorders:

• confusion, disorientation
• psychosis (loss of contact with reality)
• emotional and mood disorders
• hallucinations (seeing and possibly hearing things that are not there)
• prolonged drowsiness and sedation
• nightmares, abnormal dreams
• decreased alertness
• headaches
• dizziness
• difficulty coordinating muscles
• seizures, more frequently in premature and newborn babies

• temporary memory loss, whose duration will depend on the amount of midazolam you receive. You may experience it after treatment. In isolated cases, this effect has lasted a long time.
• drug dependence, abuse
• withdrawal symptoms, which may include seizures

Cardiovascular problems:

• low blood pressure
• slow heart rate
• vasodilation (widening of blood vessels)

Respiratory problems:

• slow breathing (respiratory depression)
• difficulty breathing (dyspnea)
• breathing stop (apnea, respiratory arrest)
• hypo

Gastrointestinal, intestinal and mouth problems:

• nausea
• vomiting
• constipation
• dry mouth

Skin problems:

• rash

• hives (urticaria)
• itching

Effects at the injection site:

• redness
• swelling of the skin
• blood clots or pain

General disorders

• fatigue (tiredness)

Traumatic injuries, poisonings and complications of therapeutic procedures

• falls and bone fractures. This risk is higher in patients taking other sedatives (including alcohol) and in the elderly.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Midazolam B. Braun

Your doctor or pharmacist is responsible for storing this medicine. They are also responsible for disposing of unused midazolam correctly.

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

Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry date is the last day of the month shown.

Do not store above 25°C.

Chemical and physical stability have been demonstrated during 24 hours at room temperature and during 3 days at 5°C. From a microbiological point of view, the dilutions should be used immediately after preparation. If not used immediately, the in-use storage times and conditions are the responsibility of the user and normally should not exceed 24 hours between 2 and 8°C, unless the dilution method precludes any risk of microbial contamination.

Store the vials in the outer packaging to protect them from light.

6. Container contents and additional information

Composition of Midazolam B. Braun

• The active ingredient is midazolam (as midazolam hydrochloride).

Each ml of Midazolam B. Braun 1 mg/ml contains 1 milligram of midazolam.

• 1 ampoule of 5 ml contains 5 milligrams of midazolam.
• 1 vial of 50 ml contains 50 milligrams of midazolam.
• 1 vial of 100 ml contains 100 milligrams of midazolam.

• The other components are: sodium chloride, 10% hydrochloric acid, and water for injectable preparations.

Appearance of the product and container contents

Midazolam B. Braun is a clear and colorless aqueous solution.

Midazolam B. Braun 1 mg/ml is presented in:

• Colorless glass ampoules of 5 ml, in packs of 10 ampoules.
• Transparent polyethylene ampoules of 5 ml, in packs of 4, 10, and 20 ampoules.
• Transparent polyethylene vials of 50 ml or 100 ml, in packs of 10 vials.

Only some pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:

• Braun Melsungen AG

Carl-Braun-Strasse 1

34212 Melsungen, Germany

Postal address:

34209 Melsungen, Germany

Phone: +495661713383

Manufacturer:

• Braun Medical, S.A.

Carretera de Terrassa 121,

Rubí

08191, Barcelona, Spain

• Braun Melsungen AG Mistelweg, 2

Berlin

D-12357

Further 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:

Warnings

Paradoxical reactions

Midazolam has been reported to cause paradoxical reactions, such as restlessness, agitation, irritability, involuntary movements (including tonic-clonic convulsions and muscle tremors), hyperactivity, hostility, delirium, rage, aggression, anxiety, nightmares, hallucinations, psychosis, inappropriate behavior, and other adverse effects on behavior, paroxysmal excitement, and attacks. These reactions may occur with high doses and/or if the injection is administered rapidly. The highest incidence of such reactions has been described in children and the elderly. If these reactions occur, consideration should be given to discontinuing the administration of the medicinal product.

Sleep apnea

Midazolam should be used with extreme caution in patients with sleep apnea syndrome and patients should be periodically monitored.

Handling

The medicinal product should be used immediately after opening.

Validity period after dilution in accordance with the instructions:

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

From a microbiological point of view, dilutions should be used immediately after preparation. If not used immediately, the in-use storage times and conditions are the responsibility of the user and normally should not exceed 24 hours between 2 and 8°C, unless the dilution has been made in controlled and validated aseptic conditions.

The product is supplied in single-dose containers. Unused contents of opened containers should be discarded immediately.

Use only if the solution is clear and colorless and the container and its safety closure are not damaged.

Consult the summary of product characteristics or package leaflet for instructions for dilution, incompatibilities, and complete prescribing information.