Flumazenil B. Braun

PACKAGE LEAFLET: INFORMATION FOR THE USER

Flumazenil B. Braun 0.1 mg/ml injectable solution

Flumazenil
Generic medicine
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, consult your doctor or pharmacist.

Contents of this leaflet

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

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

Flumazenil is an antidote for a specific group of medicines called benzodiazepines. Benzodiazepines have sedative properties, induce sleep, and relax muscles. They are used to make patients drowsy and calm them in cases of anxiety. Flumazenil can completely or partially reverse these effects.
Flumazenil B. Braun can therefore be used

• in anaesthesia, to wake you up after a surgical procedure or certain diagnostic tests
• if you have been kept under sedation in intensive care.

Flumazenil B. Braun may also be used for the diagnosis and treatment of benzodiazepine poisoning or overdose. Flumazenil B. Braun is used in children over 1 year of age to wake them up after they have received benzodiazepines to induce drowsiness during a medical procedure.

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

Do not use Flumazenil B. Braun

• if you are allergic to flumazenil or to any of the other ingredients of this medicine (listed in section 6);
• if you have been given benzodiazepines to control a life-threatening condition (for example, to control intracranial pressure or for severe epileptic seizures).

Warnings and precautions
Special caution is required

• If you have epilepsy and have received long-term treatment with benzodiazepines. In this case, administration of Flumazenil B. Braun may cause seizures.
• If you have severe brain damage (and/or unstable intracranial pressure), because Flumazenil B. Braun may increase intracranial pressure.
• If you suffer from liver disease. Your doctor will carefully adjust the dose of Flumazenil B. Braun.
• If you have previously experienced panic attacks, because Flumazenil B. Braun may trigger new attacks.
• If you are very anxious due to surgery or have had anxiety in the past. Your doctor will carefully adjust the dose of Flumazenil B. Braun.
• If you have been treated with high doses of benzodiazepines for prolonged periods, because there is a risk of withdrawal symptoms (withdrawal symptoms are listed in section 4, "Possible side effects").
• If you have alcohol or drug dependence. In this case, you are at higher risk of developing tolerance and dependence on benzodiazepines.
• If you have coronary heart disease. Your doctor must be informed, as they may decide to maintain sedation for a longer period.

Your level of alertness and vital signs (such as blood pressure, heart rate, and respiratory rate) will be monitored for an adequate period after administration of Flumazenil B. Braun. Since the action of Flumazenil B. Braun is usually shorter than that of benzodiazepines, sedation may recur. You must remain under close observation, preferably in an intensive care unit, until all possible effects of Flumazenil B. Braun have completely subsided.
If Flumazenil B. Braun is administered at the end of surgery to awaken you, it must not be used before the effects of muscle relaxants have worn off.
Your doctor will take into account the possibility of postoperative pain following invasive procedures before administering Flumazenil B. Braun.
If you do not regain consciousness after administration of Flumazenil B. Braun, another cause for the lack of awakening should be considered, as Flumazenil B. Braun specifically reverses the effects of benzodiazepines.
Your doctor will avoid injecting Flumazenil B. Braun rapidly. If you have undergone long-term (chronic) treatment with benzodiazepines, rapid injection of high doses (more than 1 mg) of Flumazenil B. Braun may cause withdrawal symptoms.
Flumazenil B. Braun is not recommended for the treatment of benzodiazepine dependence or benzodiazepine withdrawal syndromes.
Your doctor will administer Flumazenil B. Braun with particular caution in cases of mixed intoxication involving benzodiazepines and certain other antidepressants (so-called cyclic antidepressants such as imipramine, clomipramine, mirtazapine, or mianserin). The toxicity of these antidepressants may be masked by the protective effects of benzodiazepines (see also section 2, "Other medicines and Flumazenil B. Braun").
Signs of significant overdose with cyclic antidepressants include:

• dilated pupils, inability to urinate, dry mouth,
• serious or potentially life-threatening conditions such as agitation, breathing difficulties, seizures, heart problems, and coma.

Children
Children previously sedated with midazolam must be closely monitored in intensive care for at least 2 hours after administration of Flumazenil B. Braun.
Recurrence of sedation or breathing difficulties may occur. In case of sedation with other benzodiazepines, monitoring should be adjusted according to the expected duration of sedative effect.
Children aged 1 year or younger should receive Flumazenil B. Braun only if risks have been carefully weighed against the benefits of treatment.
Children should receive Flumazenil B. Braun only after intentional sedation. Available data are insufficient for any other indication. The same applies to children under 1 year of age.

Other medicines and Flumazenil B. Braun
Tell your doctor if you are taking, have recently taken, or might take any other medicines.
Flumazenil B. Braun counteracts the effect of all medicines acting through the benzodiazepine receptor, including medicines not belonging to the benzodiazepine group but having the same active substance, such as zopiclone (e.g., Zimovane), triazolopyridazines, and others.
Benzodiazepines may mask the toxic effects of certain psychotropic medicines (especially tricyclic antidepressants such as imipramine, see also section 2, "Warnings and precautions"). When using Flumazenil B. Braun in cases of accidental overdose, it must be considered that the toxic effects of these concomitantly taken medicines may increase as the effects of benzodiazepines decrease.
No interactions have been observed with other central nervous system depressants or alcohol.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Due to insufficient experience during pregnancy, Flumazenil B. Braun should be used with caution and only if the benefits to you outweigh the potential risk to the unborn child. Administration of Flumazenil B. Braun during pregnancy is not contraindicated in emergency situations.
It is not known whether flumazenil is excreted in breast milk. Therefore, you must not breastfeed for 24 hours after administration of Flumazenil B. Braun. Administration of Flumazenil B. Braun during breastfeeding is not contraindicated in emergency situations.

Driving and using machines
After receiving Flumazenil B. Braun to reverse the sedative effects of benzodiazepines, you must not drive vehicles, operate machinery, or engage in any other activities requiring physical or mental effort for at least 24 hours, as sedation may recur.

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

3. How to use Flumazenil B. Braun

Flumazenil B. Braun will be administered by an anaesthetist or an experienced doctor.
Flumazenil B. Braun is given as an intravenous injection (into a vein) or
diluted for infusion (administered intravenously over a longer period of time).
Flumazenil may be used together with other resuscitation measures.
The recommended dose is described as follows:

Nursing women, children and adolescents (1 to 17 years of age)
Reversal of intentional sedation.
Dosage level:
Inject 0.01 mg/kg body weight (maximum dose 0.2 mg) administered intravenously over a period of 15 seconds. If, after waiting 45 seconds, the required level of consciousness has not been achieved, an additional injection of 0.01 mg/kg (up to a maximum dose of 0.2 mg) may be administered.
If necessary, repeated injections at intervals of 60 seconds (up to a maximum of 4 times) may be given, up to a total maximum dose of 0.05 mg/kg or 1 mg, whichever is the lower dose that can be administered.

Neonates, infants and children under 1 year of age
There are insufficient data on the use of Flumazenil B. Braun in children below 1 year of age. Therefore, Flumazenil B. Braun should be administered to children below 1 year of age only if the potential benefits are judged to outweigh the possible risks (see also section 2 “Warnings and precautions, Children”).

Patients with impaired renal or hepatic function
In patients with impaired hepatic function, elimination of flumazenil may be delayed and careful dose adjustment is therefore recommended.
Dosage adjustment is not required in patients with impaired renal function.

If you have any doubts about the use of this medicine, consult your doctor or pharmacist.
For information intended for healthcare professionals, please refer to the dedicated section.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects can be serious. If you experience any of the following,
stop using this medicine and contact a doctor immediately.
Common (may affect up to 1 in 10 people):

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

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

• slow or fast heartbeat, premature heartbeat (extrasystoles)
• difficulty breathing
• chest pain

Not known (frequency cannot be estimated from the available data):

• seizures (in patients with epilepsy or severe hepatic insufficiency, mainly after long-term treatment with benzodiazepines or abuse of multiple medicines)
• allergic reactions may occur, including severe allergic reactions related to the response (anaphylaxis)

Other side effects include:
Common (may affect up to 1 in 10 people):

• agitation (after rapid injection, does not require treatment)
• difficulty falling asleep and staying asleep (insomnia), drowsiness
• dizziness, headache
• tremor or involuntary trembling
• dry mouth
• skin sensations (e.g. cold, heat, tingling, pressure, etc.) in the absence of stimuli (paraesthesia)
• double vision, strabismus, increased tear fluid production (increased lacrimation)
• sweating
• low blood pressure, drop in blood pressure when moving from lying down to standing up (orthostatic hypotension)
• malaise
• nausea and vomiting during post-operative use, 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 your own heartbeat (palpitations after rapid injection, do not require treatment)
• hearing abnormalities
• cough, nasal congestion
• skin flushing
• chills

Not known (frequency cannot be estimated from the available data):

• panic attacks in patients who have previously shown panic reactions
• transient increase in blood pressure (upon waking)
• emotional instability
• abnormal crying, agitation, and aggressive reactions.

If you have undergone long-term treatment with benzodiazepines, Flumazenil B. Braun
may induce withdrawal symptoms (frequency not known). Symptoms include agitation,
anxiety, emotional instability, confusion, and abnormal sensory perceptions.
In general, side effects in children are usually similar to those in adults.
If Flumazenil B. Braun is used to wake your child from sedation, abnormal crying,
agitation, and aggressive reactions may occur.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at
www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Flumazenil B. Braun

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and on the carton. The expiry date refers to the last day of that month.
Do not store above 25°C.
This medicine is for single use only.
Period of validity after first opening: the medicine must be used immediately.
Period of validity after dilution: 24 hours.
Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C.
From a microbiological standpoint, the medicine should be used immediately. If not used immediately, the storage duration in use and the conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 2–8°C, unless the dilution was carried out under controlled and validated aseptic conditions.
The solution should be inspected visually before use. Flumazenil B. Braun should only be used if the solution is clear, colourless and free from particles.
Unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Flumazenil B. Braun contains
The active substance is flumazenil.
Each millilitre contains 0.1 mg of flumazenil.
Each 5 ml vial contains 0.5 mg of flumazenil.
Each 10 ml vial contains 1.0 mg of flumazenil.
The other components are disodium edetate, glacial acetic acid, sodium chloride, 4% sodium hydroxide solution, water for injections.

Description of the appearance of Flumazenil B. Braun and contents of the pack
Flumazenil B. Braun is a clear, colourless, injectable concentrate solution in colourless glass vials.
The following pack sizes are available:
Carton boxes containing 5 or 10 vials with 5 ml of solution.
Carton boxes containing 5 or 10 vials with 10 ml of solution.
It is possible that not all pack sizes are 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

Manufacturing site
B. Braun Melsungen AG
Mistelweg, 2 Berlin, Germany

Additional manufacturer:

• Hameln Pharmaceuticals GmbH, Langes Feld 13, 31789 Hameln, Germany

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

The following information is intended exclusively for healthcare professionals:

When Flumazenil B. Braun is to be used for infusion, it must be diluted prior to infusion.
Flumazenil should only be diluted with sodium chloride solution 9 mg/ml (0.9% w/v), glucose solution 50 mg/ml (5% w/v), or sodium chloride solution 4.5 mg/ml (0.45% w/v) + glucose 25 mg/ml (2.5% w/v). Compatibility of flumazenil with other injectable solutions has not been established.
This medicinal product must not be mixed with other medicinal products except those mentioned in this section.