MIDAZOLAM B. BRAUN 5 mg/ml SOLUTION FOR INJECTION/INFUSION

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 to 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

Consult your doctor or pharmacist before starting to use Midazolam B. Braun.

You will be closely monitored while receiving the medicine. Your doctor will also ensure 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 attention 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 period, you may:

• become tolerant to midazolam. The medicine will lose its effectiveness and will not work as well for you,
• 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 a heart condition 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 or to help you sleep)
• hypnotics (sleeping medicines)
• sedatives (medicines to make you feel calm or drowsy)
• antidepressants (medicines used to treat depression)
• very potent 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 biloba or 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 manner. 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, as it may pass into breast milk.

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.

This medicine may cause you to feel drowsy and affect your concentration and coordination. Make sure someone accompanies you home when you are discharged.

Midazolam B. Braun contains sodium

This medicine contains 2.19 mg of sodium (main component of table/cooking salt) in each 1 ml ampoule. This is equivalent to 0.11% of the maximum recommended daily intake of sodium for an adult.

This medicine contains 6.58 mg of sodium (main component of table/cooking salt) in each 3 ml ampoule. This is equivalent to 0.33% of the maximum recommended daily intake of sodium for an adult.

This medicine contains 21.94 mg of sodium (main component of table/cooking salt) in each 10 ml ampoule. This is equivalent to 1.01% 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 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.

Posology:

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 control of muscles (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 appearance of skin rash, itching or skin rash with hives (urticaria) 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 potentially 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 obstruction of the airway (laryngospasm).

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

Other side effects:

Immune system disorders:

• generalized allergic reactions (skin, cardiac 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 disorders:

• 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 infants
• 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 disorders:

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

Respiratory disorders:

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

Gastrointestinal disorders:

• nausea
• vomiting
• constipation
• dry mouth

Skin disorders:

• rash
• urticaria (rash with hives)
• itching

Administration site disorders:

• 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 in use for 24 hours at room temperature and for 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 ampoules in the outer packaging to protect them from light.

6. Packaging Contents and Additional Information

Composition of Midazolam B. Braun

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

Each ml of Midazolam B. Braun 5 mg/ml contains 5 milligrams of midazolam.

• 1 ampoule of 1 ml contains 5 milligrams of midazolam,
• 1 ampoule of 10 ml contains 50 milligrams of midazolam,

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

Appearance of the Product and Packaging Contents

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

Midazolam B. Braun 5 mg/ml is presented in:

• Colorless glass ampoules of 1 ml, in packs of 10 ampoules.
• Colorless glass ampoules of 10 ml, in packs of 5 or 10 ampoules.
• Transparent polyethylene ampoules of 10 ml, in packs of 4, 10, and 20 ampoules.

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

Mailing Address:

34209 Melsungen, Germany

Phone: +495661713383

Manufacturer:

• BRAUN MEDICAL, S.A.

Ctra. de Terrassa, 121.

Rubi (Barcelona) 08191B.

Braun Melsungen AG

Carl-Braun-Strasse 1

34212 Melsungen, Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

• Braun Medical, S.A.

Carretera de Terrassa 121,

Rubí,

08191, Barcelona, Spain

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Date of the Last Revision of this Leaflet:October 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:

Warnings

Paradoxical reactions

With midazolam, paradoxical reactions have been reported, such as restlessness, agitation, irritability, involuntary movements (including tonic-clonic convulsions and muscle tremors), hyperactivity, hostility, delirium, anger, 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 according to 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. The 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.