Prospect:Information for the User

Attach 0.5mg/5ml injectable solution

Flumazenil

Read this prospect carefully before starting touseethismedication, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribedonlyto you,and you should not give it to other people even if they have the same symptomsas you, as it may harm them.
• Ifyou experience adverse effects, consult your doctor or pharmacist even if they are not listed in this prospect.See section 4.

1.What is Anexate and for what it is used

2.What you need to know before starting to useAnexate

3.Howto useAnexate

4.Possible adverse effects

5.Storage of Anexate

6.Contents of the package and additional information

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

Anexate 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 the paradoxical reactions caused by them (a paradoxical reaction is when the treatment has the opposite effect of what is normally expected).

Anexate 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 cause, in order to check if it is due to benzodiazepines, other medications or a cerebral injury.

Anexate is also used in children over 1 year old to awaken them from benzodiazepine-induced sedation.

Do not attach

• If you are allergic (hypersensitive) to flumazenil or any of the other components of this medication (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

Consult your doctor or pharmacist before starting to use Anexate. 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.

Anexate specifically corrects the effects of benzodiazepines, therefore, if you do not wake up after the administration of Anexate, consider another reason for it.

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

Since the effect of flumazenil 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 Anexate has completely disappeared.

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

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

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

Anexate 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 Anexate).

Use of Anexate with 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 Anexate. 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 Anexate, consult your doctor before taking any other medication.

Pregnancy and breastfeeding

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

The passage of Anexate into breast milk is unknown. If you are breastfeeding, do not be treated with Anexate 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 Anexate, as the effect of previously taken or administered benzodiazepines may recur.

Anexate contains sodium

Anexate 0.5 mg/5 ml injectable solution contains less than 23 mg of sodium (1 mmol) per ampoule; this is essentially "sodium-free".

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

The doses can 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.

In anesthesia

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

In intensive care units and in the diagnosis of unconsciousness of unknown origin

As an initial dose, 0.3mg i.v. is recommended. In case 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 2mg.

In case of reappearance of somnolence, Anexate may be administered as one or more bolus and it may be useful to perform an i.v. infusion of 0.1-0.4mg 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 childrenand adolescents

Children over one year

The recommended initial dose is 10 micrograms/Kg (up to 200 micrograms) administered intravenously over 15 seconds. In case the desired level of consciousness is not obtained after 45 seconds have passed, your doctor may administer, if necessary, new doses equal to the initial one at intervals of 60 seconds (up to a maximum of 4) up to a maximum total dose of 50 micrograms/Kg or 1mg, 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 sedation.

Children under one year

Since the experience is limited, Anexate 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 general anesthesia induction in children.

Until sufficient data are available, Anexate 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.

Ifyouusemore Anexate than you should

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

In case of overdose or accidental ingestion, consult the Toxicological Information Service. Phone: (91) 562 04 20.

Like all medicines, Anexate can cause side effects, although not everyone will experience them.

Anexate 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 (allergy), including anaphylaxis.

Mental health disorders

• Uncommon: anxiety and fear after a rapid administration of Anexate, usually did not require treatment.

• Frequency not known: withdrawal syndrome, with symptoms such as agitation (excitement, restlessness), anxiety (anguish, fear), emotional lability (laughter or crying attacks), 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.

In general, the 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 mixed medication overdose.

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 mixed medication overdose, 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 prospectus, 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 prospectus. You can also report them directly through the Spanish System for the 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 medicine.

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

No special storage conditions are required.

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.

Composition of Anexate

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

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

Appearance of the product and contents of the package

Anexate 0.5mg/5ml is presented as an injectable solution. Each package contains 5 ampoules of 5ml each, containing 0.5mg of flumazenil.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

CHEPLAPHARM Arzneimittel GmbH

Ziegelhof 24

17489 Greifswald

Germany

Responsible for manufacturing

CHEPLAPHARM Arzneimittel GmbH

Ziegelhof 23-24

17489 Greifswald

Germany

Local representative

Laboratorios Rubió S.A.

C/ Industria 29

Pol. Industrial Comte de Sert

08755 Castellbisbal (Barcelona)

Spain

Last review date of this leaflet: October 2020

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

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This information is intended solely for medical professionals or healthcare professionals:

Anexate is recommended for use only intravenously and should be administered by an anesthesiologist or experienced physician.

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

When Anexate 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.

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

It should be avoided to inject Anexate 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.

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