Prospecto:information for the user

Flumazenil Hikma 0.1 mg/ml injectable solution and forperfusion EFG

Flumazenil

Read this prospect carefully before starting to use this medication,because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• 1. If you have any doubts, consult yourdoctor or pharmacist.

-If you experience adverse effects,consult your doctor or pharmacist,eveniftheyare not listed in this prospect. See section 4.

1.What is Flumazenil Hikma and for what it is used

2.What you need to knowbeforestarting touse Flumazenil Hikma

3.How to use Flumazenil Hikma

4.Possible adverse effects

5Storage of Flumazenil Hikma

6.Contents of the package and additional information

Flumazenilo Hikma is an antagonist (antidote) agent to neutralize totally or partially the central sedative effect of benzodiazepines (a specific group with sedative, sleep-inducing, muscle relaxant, and anxiolytic properties).

Consequently, it should be used in anesthesia to wake them up after certain diagnostic tests or in intensive care if they have been sedated. Flumazenilo can also be used for the treatment of benzodiazepine intoxications or overdoses as well as to counteract the paradoxical reactions caused by them.

Flumazenilo Hikma can be used as a diagnostic measure in unconsciousness of unknown etiology.

No use Flumazenilo Hikma:

• if you areallergicto the active ingredient or to any of the other components of this medication (listed in section 6).
• if benzodiazepines have been administered in the control of alife-threatening situation(for example, control of high blood pressure or a severe epileptic seizure).
• in mixed intoxications with benzodiazepines and certain types of antidepressants (called tricyclic and tetracyclic antidepressants such as Imipramine, Clomipramine, Mirtazepine, or Mianserine). The toxicity of these antidepressants may be masked by the protective effects of benzodiazepines. If you present symptoms of an overdose of these antidepressants, Flumazenil Hikma should not be used to reverse the effect of benzodiazepines.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Flumazenil Hikma.

• the effect of flumazenil is shorter than that of benzodiazepines, and thereforeit is possible that sedation may recur. Therefore, you must remain under observation until all the effects of flumazenil have disappeared.
• if you have liver problems.
• if you have received long-term treatment with benzodiazepines, Flumazenil may causewithdrawal symptoms(see section 4).
• if you areepilepticand have received benzodiazepine treatment for a long period of time, the administration of flumazenil is not recommended as it may causeseizures.
• if you have asevere brain injury(for example, unstable blood pressure in the brain or severe epileptic seizure), you must be careful as Flumazenil may cause an increase in blood pressure in your brain.
• Flumazenil is not recommended for the treatment ofbenzodiazepine addictionor for thesymptoms of benzodiazepine withdrawal.
• if you have previously suffered frompanic attacks or anxiety, Flumazenil may cause new attacks.
• if you are dependent on alcohol or medications as you have a higher risk of tolerance (no beneficial effects) and dependence on the benzodiazepine.
• children and infants should only receive Flumazenil to reverseconscious sedation(in which they remain awake). Children should be monitored for at least 2 hours after administration of Flumazenil.

Use of Flumazenil Hikmawithother medications

Inform your doctor if you are using, have used recently, or may have to take any other medication.

When using flumazenil, it should be taken into account that the toxic effects of other psychotropic medications (especially tricyclic antidepressants such as Imipramine), may be increased with the decrease in the effect of benzodiazepines.

Pregnancy andlactation

If you are pregnant or breastfeeding, consultyour doctor or pharmacist before using this medication.

Due to the lack of experience during pregnancy, Flumazenil Hikma should only be used if the benefit for you is greater than the potential risk to the future child. Administration of Flumazenil during pregnancy is not contraindicated in an emergency situation.

It is not known if flumazenil passes into breast milk. Thereforeit is recommended not to breastfeed the child for 24 hoursafter administration of flumazenil.

Driving and operating machinery

Do not drive, operate any machinery, or perform any other physical activity or require mental concentration for a period of 24 hours after administration of flumazenil to reverse the sedative effects of benzodiazepines as sedation may recur.

Flumazenil Hikma contains sodium chloride

This medication contains 3.7 mg of sodium per ml of injectable solution (18.5 mg / ampoule of 5 ml or 37 mg / ampoule of 10 ml). This should be taken into account if you maintain a low-sodium diet.

Flumazenil Hikma is administered viaintravenous injection(into a vein) or diluted asintravenous infusion(over a longer period).

Flumazenil Hikma should be administered by an anesthesiologist or a doctor with experience. Flumazenil may be used simultaneously with other measures for regaining consciousness.

Your doctor will decide on the most suitable dose for you. Doses can be very variable, and will depend on your individual case. Further details for healthcare professionals are given at the end of this leaflet.

During anesthesia

The recommended initial dose is 0.2 mg i.v., administered over a period of 15 seconds. An additional dose of 0.1 mg may be injected and repeated at intervals of 60 seconds, if the required level of consciousness has not been achieved within 60 seconds, up to a maximum dose of 1.0 mg. The usual required dose is between 0.3 and 0.6 mg, but individual requirements can vary considerably, depending on the duration of the effect of the benzodiazepine administered and the patient's characteristics.

Intensive care units

The recommended initial dose is 0.3 mg administered intravenously. If, after 60 seconds, the desired level of consciousness has not been achieved, 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 awakens. If somnolence reappears, a useful intravenous infusion of 0.1 – 0.4 mg/h may be helpful. The infusion rate should be adjusted individually to achieve the desired level of consciousness.

Children under 1 year

There are insufficient data on the use of Flumazenil in children under 1 year. Therefore, Flumazenil Hikma should only be administered to children under 1 year if the potential benefits for the patient outweigh the possiblerisks.

Children over 1 year

To eliminate sedation caused by benzodiazepines in children over 1 year, the recommended initial dose is 10 micrograms/kg (up to 200 micrograms) administered intravenously over 15 seconds. If consciousness is not regained after 45 seconds, new injections of 10 micrograms/kg (up to 200 micrograms) may be administered, if necessary, every 60 seconds (up to a maximum of 4 times) up to a maximum total dose of 50 micrograms/kg or 1 mg. The dose should be calculated individually for each patient.There are no data on the safety and efficacy of repeated administration of flumazenil in children for re-sedation.

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

Patients with liver dysfunction (liver disease)

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

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

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

Frequent (can affect up to 1 in 10 people)

• nausea or vomiting, particularly if opioids have also been used.

Less frequent (can affect up to 1 in 100 people)

These effects are more likely to occur after a rapid administration and do not require treatment:

• anxiety
• fear
• awareness of your heart rate (palpitations)

Unknown frequency(cannot be estimated from available data)

• allergic reactions (allergic reactions), includingsevere allergic reactions
• panic attacks (in patients with a history of panic reactions)
• abnormal crying
• agitation
• aggressive reactions
• seizures. More likely in patients with epilepsy or severe liver failure, mainly after long-term treatment with benzodiazepines or multiple drug abuse
• transient increase in blood pressure upon waking from the effect of benzodiazepines
• redness of the face and neck
• chills (after a rapid injection, they have not required treatment)

If you have been treated for long periods with benzodiazepines/ with high doses of flumazenil may inducewithdrawal symptoms. The symptoms are:

• agitation
• anxiety
• emotional lability
• confusion
• distorted sensations (hearing voices, seeing things that do not exist, skin sensations)

The side effects in children do not differ much from adults. When flumazenil is used in children, abnormal crying, nervousness, and aggressive reactions have been observed

Reporting of side effects

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

Keepthis medicationout of the sight and reach of children.

Do not use this medication after the expiration date that appears on the label and the box. The expiration date is the last day of the month indicated.

Do not store at a temperature above 25°C.

This medication is for single use and must be administered immediately after opening.

After dilution, do not refrigerate.Chemical and physical stability has been demonstrated for 24 hours at 25°C. From a microbiological standpoint, the product should be used immediately, unless the dilution method prevents microbial contamination. If not used immediately, the useful storage time and conditions before use are the responsibility of the user.

Do not useFlumazenilo Hikmaif the solution is not transparent and free of particles.

Medications should not be disposed of through drains or trash. If in doubt, ask your pharmacist how to dispose of containers and medications that you no longer need. This will help protect the environment.

Composition of Flumazenil Hikma

The active ingredient is flumazenil.

Each milliliter of solution contains 0.1 mg of flumazenil.

Each ampoule of 5 ml contains 0.5 mg of flumazenil.

Each ampoule of 10 ml contains 1.0 mg of flumazenil.

The other components are:

• edetate disodium
• glacial acetic acid
• sodium chloride (3.7 mg/ml)
• hydrochloric acid (36%) for pH adjustment
• sodium hydroxide for pH adjustment
• water for injection

Appearance of the product and contents of the package

Flumazenil Hikma is a transparent and colorless solution for injection or for dilution before infusion.

Flumazenil Hikma is packaged in colorless glass ampoules.

It is available in the following formats:

Cartons with 5 or 50 (10x5) ampoules containing 5 ml of solution.

Cartons with 5 or 50 (10x5) ampoules containing 10 ml of solution.

Not all package sizes may be marketed.

Marketing Authorization Holder

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó, 8, 8A e 8B - Fervença

2705-906 Terrugem SNT

Portugal

Phone: +351 219 608 410

Fax: +351 219 615 102

e-mail:[email protected]

Responsible for manufacturing

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó, 8, 8A e 8B - Fervença

2705-906 Terrugem SNT

Portugal

Hikma Italia S.P.A., Viale Certosa 10, I-27100 PAVIA.

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Hikma España, S.L.U.

Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2

28108 - Alcobendas, Madrid

Spain

This medication is authorized in the member states of the European Economic Area with the following names:

Last review date of this leaflet:November 2017

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This information is intended solely for healthcare professionals:

Flumazenil should be administered intravenously by an anesthesiologist or experienced doctor.

Flumazenil can be administered as an injection or as an infusion (see dilution instructions in the next chapter).

Flumazenil can be used concomitantly with other resuscitation measures.

This medication is for single use only. It should be visually inspected before use and only used if the solution is transparent and practically free of particles.

In cases where repeated doses do not result in a clear effect on consciousness and respiratory function, it should be considered that the intoxication is not due to benzodiazepines.

When used in anesthesiology at the end of surgery, flumazenil should not be administered until the effects of peripheral muscle relaxants have completely reversed.

Due to the possible respiratory depression and sedation, children previously sedated with midazolam should be monitored for at least 2 hours after flumazenil administration. In the case of other benzodiazepines, the monitoring time should be adjusted according to the expected duration.

How to store Flumazenil Hikma

When flumazenil is used as an infusion, it should be diluted before infusion. Flumazenil should only be diluted with sodium chloride 9 mg/ml (0.9% w/v) or glucose 50 mg/ml (5% w/v) solution. The compatibility of flumazenil with other injectable solutions has not been demonstrated.

From a microbiological point of view, the product should be used immediately, unless the dilution method excludes the risk of microbial contamination. If not used immediately, the time and conditions of storage before use are the responsibility of the user. Do not refrigerate. Chemical and physical stability of the specialty has been demonstrated for 24 hours at 25°C.

Flumazenil Hikma should not be mixed with other medications except those mentioned above.

Recommended doses for Flumazenil Hikma

Adults:

Anesthesia

The recommended initial dose is 0.2 mg administered intravenously over 15 seconds. If, after 60 seconds, the desired level of consciousness has not been achieved, another dose of 0.1 mg may be administered and repeated at intervals of 60 seconds, up to a maximum dose of 1.0 mg. The usual required dose ranges from 0.3 to 0.6 mg, but may vary depending on the patient's characteristics and the benzodiazepine used.

Critical care

The recommended initial dose is 0.3 mg administered intravenously. If, after 60 seconds, the desired level of consciousness has not been achieved, another dose of 0.1 mg may be administered and repeated at intervals of 60 seconds, up to a total dose of 2 mg or until the patient awakens.

In cases of reappearance of somnolence, an intravenous infusion of 0.1-0.4 mg/h may be useful.

The dosage and infusion rate should be adjusted individually to achieve the desired level of consciousness.

In cases where repeated doses do not result in a clear effect on consciousness and respiratory function, it should be considered that the intoxication is not due to benzodiazepines.

The infusion should be stopped every 6 hours to check if sedation occurs again.

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

Geriatric population

No data are available on the use of flumazenil in elderly patients, but it should be noted that this population is generally more sensitive to the effects of medications, and therefore should be treated with caution.

Pediatric population

Children over 1 year of age

To reverse sedation of consciousness induced by benzodiazepines in children over 1 year of age, 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 achieved after an additional 45 seconds, another injection of 10 micrograms/kg (up to 200 micrograms) may be administered and repeated at intervals of 60 seconds (up to a maximum of 4 times) until a total dose of 50 micrograms/kg or 1 mg is reached, which represents the lowest dose. The dose should be individualized based on the patient's response. No data are available on the safety and efficacy of repeated administration of flumazenil in children for re-sedation.

Children under 1 year of age

No sufficient data are available on the use of flumazenil in children under 1 year of age. Therefore, flumazenil should only be administered in children under 1 year if the potential benefits for the patient outweigh the possible risks.

Patients with hepatic or renal impairment

As flumazenil is primarily metabolized in the liver, a careful evaluation of the dose is recommended in patients with impaired liver function. No dose adjustments are required in patients with renal impairment.