Package Insert: Information for the User

Flumazenil Accord 0.1 mg/mL Injectable Solution

Read this package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you and should not be given to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist even if they are not listed in this package insert. See section 4.

Flumazenilo Accord contains an active ingredient called flumazenil, which is an antagonist of a group of medications called benzodiazepines.

Flumazenil is used to neutralize the sedative or general anesthetic effect of benzodiazepines in patients undergoing short diagnostic or therapeutic procedures, as well as to counteract paradoxical reactions caused by them (a paradoxical reaction is when the treatment has the opposite effect of what is normally expected).

Flumazenil is used for diagnostic and/or therapeutic purposes in benzodiazepine overdoses in hospitalized patients in intensive care units. As a diagnostic measure in unconsciousness of unknown etiology, in order to check if it is due to benzodiazepines, other medications or a cerebral injury.

Flumazenil is also used in children over 1 year old to wake them up from benzodiazepine-induced sedation.

No use Flumazenilo Accord 0,1 mg/ml solución inyectable:

• If you are allergic to the active ingredient or to any of the other components of this medication (including those listed in section 6).

• If you are being treated with benzodiazepines to control situations that could potentially put your life at risk (elevated intracranial pressure, epileptic states).

If you have taken benzodiazepines and other antidepressants (tricyclic antidepressants) simultaneously and have become ill.

Warnings and precautions 0,1

Consult your doctor or pharmacist before starting to use flumazenilo. Inform your doctor if:

• You have a severe brain injury (and/or unstable intracranial pressure),
• You have epilepsy,
• You have severe liver problems,
• You have been treated with benzodiazepines for a long time,
• You have heart problems,
• You have a history of chronic or transient anxiety.

Flumazenilo specifically corrects the effects of benzodiazepines, therefore, if you do not wake up after the administration of flumazenilo, another reason should be considered.

It should not be administered during anesthesia until it has been confirmed that the peripheral muscle relaxant effects have disappeared.

Since the effect of flumazenilo is usually shorter than that of benzodiazepines, it is possible that sedation may recur. Therefore, you will be closely monitored preferably in the intensive care unit, until the effect of flumazenilo has completely disappeared.

After major surgery, postoperative pain should be taken into account and it may be preferable to keep you lightly sedated.

In the event of a mixed medication overdose, flumazenilo will be administered with special caution due to the possible appearance of toxic effects of the other medications (seizures and heart rhythm disturbances).

If you have been treated with flumazenilo to counteract the effects of benzodiazepines, you should be monitored for the necessary time to prevent the appearance of adverse effects.

Flumazenilo is not recommended for the treatment of benzodiazepine dependence or for the treatment of withdrawal symptoms from benzodiazepines.

Children and adolescents

As a general rule, it is recommended not to use this medication in children under one year (see section 3 How to use Flumazenilo Accord).

Use of flumazenilowith other medications

Inform your doctor or pharmacist that you are taking, have taken, or may need to take any other medication.

Certain medications may interact with flumazenilo. It is essential to inform your doctor if you take any of the following medications:

• Benzodiazepines.
• Non-benzodiazepine agonists such as zopiclone, triazolopyridazines, and other antidepressants.

After being treated with flumazenilo, consult your doctor before taking any other medication.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

The passage of flumazenilo into breast milk is unknown. If you are breastfeeding, you should not be treated with flumazenilo except in emergency cases and by parenteral route. Your doctor will decide what is best for your case.

Driving and operating machinery:

Do not drive because this medication may affect your ability to drive or operate machinery for 24 hours after being treated with flumazenilo, as the effect of the previously taken or administered benzodiazepines may recur.

Flumazenilo Accord contains sodium

This medication contains 33.7 mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 1.68% of the recommended daily maximum sodium intake for an adult.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The doses may be very variable, and will depend on your particular case. The dose you will receive may also depend on your weight, age, general health status, the level of sedation you have, as well as your response to this medication.

Use in anesthesia

The recommended initial dose is 0.2 mg administered intravenously over 15 seconds. If the desired level of consciousness is not obtained within 60 seconds after the first administration, your doctor will administer a new dose of 0.1 mg, repeating it, if necessary, at intervals of 60 seconds, up to a maximum total dose of 1 mg. The usual dose is between 0.3 and 0.6 mg.

Use in intensive care and in the diagnosis of unconsciousness of unknown origin

As an initial dose, 0.3 mg is recommended intravenously. If the desired level of consciousness is not obtained within 60 seconds, your doctor will administer a new dose of 0.1 mg, repeating it, if necessary, at intervals of 60 seconds up to a total dose of 2 mg.

If somnolence reappears, flumazenil may be administered as one or more bolus and it may be useful to perform an i.v. infusion of 0.1-0.4 mg per hour, adjusting the infusion rate individually according to the desired level of consciousness.

If unexpected signs of overstimulation appear, diazepam or midazolam should be administered carefully dosed intravenously according to the patient's response. In anesthesia, it is recommended to inject 5 mg of the active principles mentioned intravenously.

Use in children and adolescents

Children over one year old

The recommended initial dose is 10 micrograms/Kg (up to 200 micrograms) administered intravenously over 15 seconds. If the desired level of consciousness is not obtained after 45 seconds, your doctor may administer, if necessary, new doses at intervals of 60 seconds (up to a maximum of 4) up to a maximum total dose of 50 micrograms/Kg or 1 mg, using the dose that is less of both. There are no data on the safety and efficacy of repeated administration of flumazenil in children, in case of resedation.

Children under one year old

Given the limited experience, flumazenil should be used with caution in the recovery of conscious sedation in children under 1 year, for the treatment of poisoning in children, neonatal resuscitation, and to reverse the sedative effects of benzodiazepines used for the induction of general anesthesia in children.

Until sufficient data are available, flumazenil should not be used in children under 1 year, unless the risks to the patient (especially in case of accidental overdose) have been evaluated against the benefits of treatment.

If you use more Flumazenil Accord than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

Although no symptoms of overdosing have been observed, if you have been administered more flumazenil than you should, consult your doctor or pharmacist immediately.

If you have any other doubts about the use of this product, ask your doctor or pharmacist.

Like all medicines, Flumazenil Accord may cause side effects, although not everyone will experience them. Flumazenil is well tolerated in children and adults. In adults, it is well tolerated even at doses higher than those recommended.

The frequency of these side effects is classified in the following categories:

• Very common: may affect more than 1 in 10 patients
• Common: may affect up to 1 in 10 patients
• Uncommon: may affect up to 1 in 100 patients
• Rare: may affect up to 1 in 1000 patients
• Very rare: may affect up to 1 in 10,000 patients
• Frequency not known: the frequency cannot be estimated from the available data.

These reactions usually disappear quickly without the need for special treatment.

Immune system disorders

• Frequency not known: May appear hypersensitivity reactions (allergies), including anaphylaxis.

Mental health disorders

• Uncommon: anxiety and fear after a rapid administration of flumazenil, usually did not require treatment
• Frequency not known: withdrawal syndrome, with symptoms such as agitation (excitement, restlessness), anxiety (anguish, fear), emotional lability (attacks of laughter or crying), confusion, and sensory distortions (illusions, hallucinations).

These symptoms may occur after a rapid administration of flumazenil in patients with high doses and/or treated for prolonged periods with benzodiazepines.

Panic attacks (in patients with a history of panic reactions), abnormal crying, agitation, and aggressive reactions.

Generally, side effects in children are similar to those of adults. When this medication has been used to awaken the child from sedation, abnormal crying, agitation, and aggressive reactions have been reported.

Nervous system disorders

• Frequency not known: Seizures in patients with epilepsy or severe liver problems, especially after long treatments with benzodiazepines or in cases of overdose with mixed medications.

Cardiac disorders

• Uncommon: Palpitations (strong and rapid heartbeats) after a rapid administration of flumazenil.

Vascular disorders

• Frequency not known: Temporary increase in blood pressure (upon awakening).

Gastrointestinal disorders

• Common: Postoperative nausea and vomiting, especially if opioids (narcotics) have also been used.

Skin and subcutaneous tissue disorders

• Frequency not known: Redness.

General disorders and administration site conditions

• Frequency not known: Chills, after a rapid administration of flumazenil.

In the case of overdose with mixed medications, especially with tricyclic antidepressants, toxic effects such as seizures or cardiac arrhythmias may appear, these effects may occur when flumazenil reverses the effect of benzodiazepines.

If you consider that any of the side effects you are experiencing is severe or if you notice any side effect not mentioned in this leaflet, inform your doctor or pharmacist.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es/. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

Do not store at a temperature above 30°C.

Do not use this medication after the expiration date that appears on the packaging after CAD.

The expiration date is the last day of the month indicated. Medications should not be disposed of through drains or in the trash. Dispose of the packaging and medications you no longer need at the SIGRE collection pointof the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Flumazenil Accord

The active principle is flumazenil. Each milliliter of solution contains 0.1mg of flumazenil.

The other components are: sodium edetate, glacial acetic acid, sodium chloride, sodium hydroxide, and water for injectable preparations.

Appearance of the product and contents of the package

Flumazenil Accord is presented as an injectable solution. Each package contains 5 ampoules of 5 ml each containing 0.5 mg of flumazenil and boxes of 5 ampoules of 10 ml each containing 1 mg of flumazenil.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization:

Accord Healthcare S.L.U.

World Trade Center,

Moll de Barcelona, s/n Edifici Est, 6th floor

08039 Barcelona

Responsible for manufacturing:

Alcalá Farma, S.L.

Avenida de Madrid, 82, Alcalá de Henares,

28802 Madrid (Spain)

Date of the last review of this leaflet:March 2022

“Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/”

This information is intended solely for doctors or healthcare professionals:

Flumazenil Accord is recommended for use only intravenously and should be administered by an anesthesiologist or experienced doctor.

Flumazenil Accord may be administered diluted or undiluted. Flumazenil Accord is compatible with 5% glucose solutions in water, Ringer lactate solutions, and normal saline solutions.

When Flumazenil Accord is extracted and taken to a syringe, or mixed with any of these solutions, the solution must be discarded after 24 hours. It must be dosed carefully to achieve the desired effect.

Flumazenil Accord may also be used in conjunction with other resuscitation measures. Since the duration of action of some benzodiazepines exceeds that of Flumazenil Accord, repeated doses may be required if sedation reappears after awakening.

It should be avoided to inject Flumazenil Accord rapidly. In patients receiving high doses and/or prolonged treatment with benzodiazepines in the weeks preceding its administration, rapid injection of doses equal to or greater than 1 mg may cause withdrawal symptoms, including palpitations, agitation, anxiety, emotional lability, as well as mild confusion and sensory distortions.

Flumazenil Accord is not recommended for the treatment of benzodiazepine dependence or for the control of symptoms of withdrawal caused by benzodiazepines.