Package Insert: Information for the User

FLUMAZENIL ALTAN 0.1 mg/mL Injectable Solution EFG

Read the entire package insert carefully before starting to use the medication

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any adverse effects, consult your doctor or nurse, even if they are not listed in this package insert. See section 4

Flumazenil has an opposite action and neutralizes the effect of benzodiazepines (compounds used for their sedative, muscle relaxant, and anticonvulsant properties) and belongs to the group of antidotes. Its action consists of interrupting the nerve conduction produced by benzodiazepines by competing with them in their union to the nervous system receptors.

This medication is indicated to neutralize totally or partially the central sedative effect of benzodiazepines. Consequently, it should be used in anesthesia and intensive care in the following indications:

In anesthesia:

• To end anesthesia produced by benzodiazepines in hospitalized patients.
• To end the calming or sedative effect produced by benzodiazepines in patients who have undergone tests for diagnosis or identification of a disease, or in short treatments in the hospital or outpatient setting.

In intensive care:

• To reverse the effect of benzodiazepines at the central nervous system level and allow for the recovery of spontaneous breathing.

To diagnose or treat intoxications or overdoses caused solely or mainly by benzodiazepines.

No use FLUMAZENIL:

• In case of being allergic to flumazenil or to any of the other components of this medication.
• In cases of intoxications due to two drugs such as benzodiazepines and tricyclic antidepressants (compounds used in the treatment of depression), because the toxicity of antidepressants may be masked by the protective effects of benzodiazepines.
• If benzodiazepines have been used as treatment for a potentially life-threatening disease (for example, control of intracranial pressure or status epilepticus).

Warnings and precautions for use:

• It is not recommended to use in children for indications other than terminating the calming or sedative effect. This also applies to children under one year in which flumazenil should not be used unless the potential benefits outweigh the possible risks.
• If the patient does not wake up because it may be due to another cause. If used to terminate anesthesia after surgery, it should not be administered until the muscle-relaxing effect has ended. Since the action of flumazenil is normally shorter than that of benzodiazepines and the sedative effect may reappear, the patient should be closely monitored, preferably in the intensive care unit, until the effect of flumazenil has disappeared.
• In cases of patients at risk, the advantages of sedation with benzodiazepines should be weighed against the disadvantages that would occur if a rapid awakening were to occur. In some patients, such as those with heart problems, a certain degree of sedation may be preferred over complete awakening.
• High doses (over 1 mg) of flumazenil should be avoided in patients receiving long-term treatment with benzodiazepines, as this could cause withdrawal symptoms.
• The dose of flumazenil should be carefully adjusted in patients who have anxiety before surgery or who have a history of anxiety or anxiety disorders.
• If pain occurs after surgery.
• If you have been taking high doses of benzodiazepines for a long time. In patients with epilepsy treated with benzodiazepines for a prolonged period, sudden neutralization of the effect could cause seizures.
• If you have severe brain injuries, as it may increase intracranial pressure.
• If you have dependence or benzodiazepine withdrawal syndrome, treatment with flumazenil is not recommended.
• If you have a history of panic disorders.
• Due to the increased frequency of tolerance and dependence to benzodiazepines in patients with alcoholism and dependence on other drugs, flumazenil should be used with caution in this population.
• Patients treated with this medication to neutralize the effects of benzodiazepines should be monitored at all times necessary, depending on the duration of the benzodiazepine effect, to prevent the occurrence of breathing problems, drowsiness, or any other effect due to the benzodiazepine.

Use of other medications:

Inform your doctor or pharmacist if you are taking or have recently taken any other medication, including those purchased without a prescription.

This medication counteracts the effects of benzodiazepines in the Central Nervous System; the action of other medications, such as zopiclone (used in the treatment of sleep disorders), triazolopyridazines (non-benzodiazepine anxiolytics), and others, is also counteracted by flumazenil.

Pregnancy and lactation

Consult your doctor or pharmacist before taking a medication.

If you are pregnant, you will only use this medication under strict indication from your doctor.

The parenteral administration of flumazenil in emergencies during lactation is not contraindicated.

Driving and use of machines:

Although after intravenous administration of this medication, patients may be awake and conscious, they should abstain from performing hazardous activities that require full mental concentration (such as operating hazardous machinery or driving vehicles) for 24 hours, as the effects of the previously taken or administered benzodiazepine, such as sedation, may reappear.

Important information about one of the components of Flumazenil

This medication contains 9 mg of sodium per ml; this is, 45 mg per 5 ml ampoule and 90 mg per 10 ml ampoule of injectable solution, so it should be taken into account in patients with a low-sodium diet.

This medication is presented as an injectable solution in ampoules. Each package contains 5 ampoules.

Follow these instructions unless your doctor has given you different instructions.

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

Your doctor will indicate your daily dose and the duration of your treatment.

Since the duration of action of some benzodiazepines exceeds that of this medication, repeated doses may be required if sedation reappears after waking up.

Adults

During anesthesia

The recommended initial dose is 0.2 mg i.v., administered in 15 seconds. If the desired level of consciousness is not obtained within 60 seconds after the first i.v. administration, a new dose of 0.1 mg may be injected, repeating it, if necessary, at intervals of 60 seconds, up to a total dose of 1 mg. The usual dose is between 0.3 and 0.6 mg, but individual requirements may vary significantly, depending on the dose and duration of the benzodiazepine effect and patient characteristics.

Intensive care units

The recommended initial dose is 0.2 mg administered intravenously over 15 seconds. If, after 60 seconds, the desired level of consciousness is not obtained, an additional dose of 0.1 mg may be injected and repeated at intervals of 60 seconds, up to a total dose of 2 mg or until the patient wakes up.

If sedation reappears, a useful intravenous infusion of 0.1-0.4 mg/h may be useful. The infusion rate should be adjusted individually to achieve the desired level of consciousness.

If, after repeated dosing, no evident effect is obtained on consciousness and respiration, it should be considered that the intoxication is not caused by benzodiazepines.

The infusion should be interrupted every 6 hours to check if the patient is sedated again.

To avoid the appearance of abstinence in patients treated for a long period with high doses of benzodiazepines in the intensive care unit, the dose of flumazenil should be evaluated individually and the injection should be administered slowly.

Children over 1 year:

To eliminate sedation caused by benzodiazepines in children over 1 year, the recommended initial dose is 0.01 mg/kg (up to 0.2 mg) administered intravenously over 15 seconds. If consciousness is not recovered after 45 seconds, new injections of 0.01 mg/kg (up to 0.2 mg) may be administered, if necessary, every 60 seconds (up to a maximum of 4 times) until a maximum total dose of 0.05 mg/kg or 1 mg (the lower dose should be used). The dose should be calculated individually for each patient.

Use in children under 1 year:

There are not enough data on the use of flumazenil in children under 1 year. Your doctor will consider whether the potential benefits in children under 1 year outweigh any possible risks.

Use in people over 65 years:

Use in people over 65 years should be done with caution, as this population is generally more sensitive to the effects of medications.

Patients with liver and kidney function abnormalities:

In patients with liver function abnormalities, the elimination of flumazenil may be delayed, so it is recommended to reduce doses when repeated doses are administered (not for the initial dose).

No dose adjustments are required in patients with kidney problems.

If you use more FUMAZENIL ALTAN than you should:

If you think you have been given too much flumazenil, you may not notice any effect, however, it is recommended to consult your doctor or pharmacist as soon as possible.

If you have any other questions about the use of this product, ask your doctor or pharmacist. In case of overdose or accidental ingestion, consult the Toxicological Information Service. Phone: (91) 562 04 20.

If you have any other questions about the use of this medication, ask your doctor or nurse.

Like all medications, this medication may have adverse effects, although not everyone will experience them.

The following adverse effects have been described:

Very frequent: may affect more than 1 in 10 patients/people:

• nausea (during anesthesia)

Frequent (may affect up to 1 in 10 patients):

• allergic reactions
• anxiety, mood changes, insomnia, drowsiness
• dizziness, headache, nervousness, tremors, dry mouth, excessively deep and prolonged breathing, speech alterations, paresthesia.
• double vision, strabismus, increased tearing
• rapid heart rate
• flushing of the face, decreased blood pressure, decreased blood pressure upon changing position, temporary increase in blood pressure (upon waking)
• vomiting (during anesthesia), hiccups.
• sweating
• fatigue, pain at the injection site.

Rare: may affect between 1 and 10 in 1,000 patients/people

• abnormal hearing.
• increased or decreased heart rate, premature heart beat.
• difficulty breathing, cough, nasal congestion, chest pain.
• chills.

In patients treated for a long time with benzodiazepines, flumazenil may produce what is known as withdrawal syndrome, whose symptoms are: tension, agitation, anxiety, confusion, hallucinations, tremors, and seizures.

The adverse effects that may appear in children are quite similar to those of adults. When flumazenil is used to eliminate central sedation, abnormal crying, agitation, and aggressive behavior may occur.

If these adverse effects or any other not described in this prospectus are observed, consult with your doctor or pharmacist.

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

No special storage conditions are required.

Do not dispose of medications through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications you no longer need. This will help protect the environment.

Expiration Date:

Do not use this medication after the expiration date indicated on the packaging.

Composition of FLUMAZENIL ALTAN

The active ingredient is Flumazenil.

Each ml contains 0.1 mg of flumazenil.

1 vial with 5 ml contains 0.5 mg of flumazenil

1 vial with 10 ml contains 1 mg of flumazenil

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

Appearance of the product and contents of the package

5 glass vials with 0.5 mg of active ingredient in 5 ml of aqueous solution or with 1 mg of active ingredient in 10 ml of aqueous solution.

Marketing Authorization Holder:

Altan Pharmaceuticals, S.A.

C/ Cólquide nº 6. Portal 2, 1st floor,

Edificio Prisma

28230 - Las Rozas. MADRID

Spain

Responsible for manufacturing:

Laboratorio Reig Jofré, S.A.

c/ Gran Capitán, nº 10.

08970 Sant Joan Despí. (Barcelona)

Spain

This leaflet was revised in July 2019

The detailed information of this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.es

This information is intended solely for doctors or healthcare professionals:

Any unused solution must be discarded.

The medication must be visually inspected. It should only be used if the solution is transparent and practically free of particles.

When flumazenil is to be used for infusion, it must be diluted before infusion. Flumazenil should only be diluted with a 9 mg/ml sodium chloride solution (0.9%), a 50 mg/ml dextrose solution (5%), or a Ringer Lactate solution. The compatibility between flumazenil and other injectable solutions has not been established.

Solutions for intravenous infusion or syringes filled with a flumazenil solution must be discarded after 24 hours.

From a microbiological point of view, the product must be used immediately. If not used immediately, the time and storage conditions before use are the responsibility of the user and should not normally exceed 24 hours between 2 and 8°C, unless the dilution has been made in conditions appropriate to prevent contamination.