FLUMAZENIL B. BRAUN 0.1 mg/ml INJECTABLE SOLUTION

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

Do not use Flumazenil B. Braun

• If you are allergicto flumazenil or any of the other ingredients of this medicine (listed in section 6).
• If you have been given benzodiazepines to control a life-threatening situation(e.g., control of brain pressure or a severe epileptic seizure)

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you start using Flumazenil B. Braun.

Special care should be taken

• If you are epileptic and have received long-term treatment with benzodiazepines, administration of flumazenil may cause seizures.
• If you have severe brain damage (and/or unstable brain pressure), as Flumazenil B. Braun may cause an increase in brain pressure.
• If you have liver disease. Your doctor will carefully adjust the administration of Flumazenil B. Braun.
• If you have had panic attacks in the past, as Flumazenil B. Braun may cause new attacks.
• If you are very nervous due to your operation or if you have a history of anxiety. Your doctor will carefully adjust the administration of Flumazenil B. Braun.
• If you have been treated for long periods with high doses of benzodiazepines, as there is a risk of withdrawal symptoms (withdrawal symptoms are listed in section 4, "Possible side effects").
• If you are addicted to alcohol or drugs. In this case, you have a higher risk of tolerance to benzodiazepines and dependence.
• If you have coronary heart disease. You should inform your doctor so that you can be kept under sedation for a longer period.

Your level of alertness and vital signs (such as blood pressure, heart rate, and breathing) will be monitored for a suitable period after you have received flumazenil. As the action of flumazenil is usually shorter than that of benzodiazepines, sedation may recur.You will be closely monitored, possibly in the intensive care unit, until the effects of Flumazenil have completely disappeared.

If flumazenil is administered to you at the end of your operation to wake you up, it should not be administered until the effects of muscle relaxants have disappeared.

Your doctor will consider the possibility of post-operative pain after major surgery before giving you Flumazenil B. Braun.

If you do not wake upafter administration of flumazenil, another reason for this should be considered, as flumazenil specifically reverses the effects of benzodiazepines.

Your doctor will avoid rapid injection of Flumazenil B. Braun. If you have received prolonged treatment (chronic) with benzodiazepines, rapid injectionof high doses of Flumazenil B. Braun (more than 1 mg) may cause withdrawal symptoms.

Flumazenil B. Braun is not recommended for the treatment of benzodiazepine dependenceor benzodiazepine withdrawal symptoms.

Your doctor will administer Flumazenil B. Braun with special caution in case of mixed overdoses with benzodiazepines and certain types of antidepressants (so-called tricyclic antidepressants such as imipramine, clomipramine, mirtazapine, or mianserin). The toxicity of these antidepressants can be masked by the protective effects of the benzodiazepine (see also section 2, "Use of Flumazenil with other medicines"). Signs of a significant overdose with tricyclic antidepressants include:

• pupil dilation, inability to urinate, dry mouth,
• serious or potentially life-threatening conditions such as agitation, respiratory problems, seizures, heart problems, and coma.

Children

Children who have been previously sedated with midazolam should be closely monitored in the intensive care unit for at least 2 hours after administration of Flumazenil B. Braun. Re-sedation or respiratory difficulties may occur.

In the case of sedation with other diazepines, monitoring should be adjusted according to the expected duration.

Children under 1 year of age should only receive flumazenil if the risks have been carefully weighed against the benefits of treatment.

Children should only receive flumazenil after intentional sedation.There is not enough data for any other indication. The same applies to children under 1 year of age.

Use of Flumazenil B. Braun with other medicines

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

Flumazenil counteracts the effect of all medicines that act through the benzodiazepine receptor. This includes medicines that do not belong to the group of benzodiazepines but have the same active ingredient, such as zopiclone (e.g., Zimovane), triazolopyridazine, and others.

Benzodiazepines can mask the toxic effects of certain psychotropic medicines (especially tricyclic antidepressants such as imipramine; see also section 2, "Warnings and precautions"). When flumazenil is used in cases of accidental overdose, it should be taken into account that the toxic effects of concomitantly taken medicines may increase with the disappearance of the benzodiazepine effect.

No interaction has been observed with alcohol or other central nervous system depressants.

Pregnancy and breastfeeding

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

Due to insufficient experience during pregnancy, Flumazenil B. Braun should only be used with caution and only if the benefitto you is greater than the potential riskto the fetus. Administration of Flumazenil during pregnancy is not contraindicated in an emergency situation.

It is not known whether Flumazenil is excreted in breast milk. You should not breastfeed for 24 hoursafter administration of Flumazenil B. Braun. Administration of Flumazenil B. Braun during breastfeeding is not contraindicated in an emergency situation.

Driving and using machines

After receiving Flumazenil B. Braun to correct the sedative effects of benzodiazepines, you should not drive, operate machinery, or start any other activitythat requires physical or mental effort for at least 24 hours, as sedation may recur.

Flumazenil B. Braun contains sodium

This medicine contains less than 23 mg (1 mmol) of sodium per ml (injectable solution), so it is essentially "sodium-free".

3. How to use Flumazenil B. Braun

Flumazenil should be administered by your anesthetist or experienced doctor. Flumazenil B. Braun is administered as an injectioninto a vein or diluted as an infusioninto a vein (over a prolonged period)

Flumazenil can be used at the same time as other resuscitation measures.

The recommended dose is as follows:

Newborns, infants under 1 year

There is not enough data on the use of flumazenil in children under 1 year of age.

Therefore, flumazenil should only be administered in children under 1 year of age if the potential benefitsto the patient outweigh the possible risks(see also section 2, "Warnings and precautions").

Patients with renal (kidney) or hepatic (liver) dysfunction

In patients with liver dysfunction, the elimination of flumazenil may be delayed, and therefore, careful dose adjustmentis recommended.

In patients with kidney dysfunction, dose adjustment is not required.

Follow the instructions for administration of this medicine exactly as told by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

For information for healthcare professionals, please see the corresponding section below.

4. Possible side effects

Like all medicines, Flumazenil B. Braun can cause side effects, although not everybody gets them.

The following side effects may be serious. If you think you have any of these side effects, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Common(may affect up to 1 in 10 people):

• abnormal rapid and deep breathing (hyperventilation)
• speech disorders

Uncommon(may affect up to 1 in 100 people):

• slow or fast heart rate, premature heartbeat (extrasystole)
• difficulty breathing
• chest pain

Frequency not known(cannot be estimated from the available data):

• seizures (in patients who suffer from epilepsy or severe liver failure, especially after long-term treatment with benzodiazepines or abuse of multiple medicines)
• allergic reactions, including severe allergic reactions related to the response (anaphylaxis), may occur

Other side effects include:

Common(may affect up to 1 in 10 people):

• agitation (after rapid injection, does not require treatment)
• problems with sleep initiation and maintenance (insomnia), feeling of sleep (somnolence)
• dizziness, headache
• involuntary trembling movements or tremors
• dry mouth
• subjective skin sensations (e.g., cold, heat, tingling, pressure, etc.) in the absence of stimulation (paresthesia)
• double vision, squinting (strabismus), increased tear production (increased lacrimation)
• sweating
• low blood pressure, low blood pressure when changing from a lying to a standing position (orthostatic hypotension)
• discomfort: vomiting (after surgery), hiccups
• fatigue
• pain at the injection site

Uncommon(may affect up to 1 in 100 people):

• anxiety and fear (after rapid injection, does not require treatment)
• awareness of heartbeat (palpitations, which occur after rapid injection, does not require treatment)
• abnormal hearing
• cough, nasal congestion
• redness of the skin
• chills

Frequency not known(cannot be estimated from the available data):

• panic attacks in patients who have already shown panic reactions
• transient increase in blood pressure (when waking up)
• emotional lability
• abnormal crying, agitation, and aggressive reactions

If you are treated for prolonged periods with benzodiazepines, flumazenil may induce withdrawal symptoms (frequency not known). The symptomsinclude: agitation, anxiety, emotional weakness, confusion, and abnormal sensory perception.

In general, the undesirable effectsin childrenare similar to those in adults. When Flumazenil B. Braun is used to wake up your child from sedation, abnormal crying, agitation, and aggressive reactions may occur.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. 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: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Flumazenil B. Braun

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

Do not use Flumazenil B. Braun after the expiry date which is stated on the label and carton. The expiry date is the last day of the month stated.

Do not store above 25°C.

This medicine is for single use only.

Shelf-life after first opening of the container: the medicine should be used immediately.

Shelf-life after dilution: 24 hours.

Chemical and physical stability has been demonstrated for 24 hours at 25°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless the dilution has been made in controlled and validated aseptic conditions.

The solution should be inspected visually before use. Do not use Flumazenil B. Braun if the solution is not clear, colorless, and free of particles.

Any unused solution should be disposed of in accordance with local requirements.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container contents and additional information

Composition of Flumazenil B. Braun

The active ingredientis flumazenil.

Each milliliter contains 0.1 mg of flumazenil.

Each ampoule with 5 ml contains 0.5 mg of flumazenil.

Each ampoule with 10 ml contains 1.0 mg of flumazenil.

The other componentsare: disodium edetate, glacial acetic acid, sodium chloride, 4% sodium hydroxide solution, and water for injection.

Appearance of the product and container contents

Flumazenil B. Braun is a clear and colorless solution for infusion in colorless glass ampoules.

The following package sizes are available:

Boxes with 5 or 10 ampoules containing 5 ml of solution.

Boxes with 5 or 10 ampoules containing 10 ml of solution.

Not all package sizes may be marketed.

Marketing authorization holder and manufacturer

• Braun Melsungen AG

Carl-Braun-Strasse 1

34212 Melsungen, Germany

Mailing address:

34209 Melsungen, Germany

Phone: +49/5661/71-0

Fax: +49/5661/71-4567

This medicinal product is authorized in the EEA Member States under the following names:

By the applicant B. Braun

Date of last revision of this leaflet: 02/2018

The detailed informationof this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products. http://www.aemps.gob.es/

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This information is intended only for healthcare professionals:

If Flumazenil B. Braun is to be used for infusion, it must be diluted before use. Flumazenil should only be diluted with sodium chloride 9 mg/ml (0.9%) solution, glucose 50 mg/ml (5%) solution, or sodium chloride 4.5 mg/ml (0.45%) + glucose 25 mg/ml (2.5%) solution. The compatibility of Flumazenil with other injectable solutions has not been determined.

This medicinal product must not be mixed with other medicinal products except those mentioned in this section.