FLUMAZENIL HIKMA 0.1 mg/mL Injectable Solution and Infusion

Introduction

Package Leaflet:information for the user

Flumazenil Hikma 0.1 mg/ml solution for injection and infusion EFG

Flumazenil

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• 1. If you have any further questions, ask your doctor or pharmacist.

• If you experience any side effects, talk to your doctor or pharmacist, even if it is not listed in this leaflet. See section 4.

Contents of the pack

1. What is Flumazenil Hikma and what is it used for
2. What you need to know before you use Flumazenil Hikma
3. How to use Flumazenil Hikma
4. Possible side effects

5 Storage of Flumazenil Hikma

1. Contents of the pack and further information

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

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

Consequently, it should be used in anesthesia to wake you up after certain diagnostic tests or in intensive care if you have been kept sedated. Flumazenil can also be used to treat overdoses or poisonings with benzodiazepines as well as to counteract the paradoxical reactions caused by them.

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

2. What you need to know before you use Flumazenil Hikma

Do not use Flumazenil Hikma:

• if you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
• If benzodiazepines have been administered to control a life-threatening situation(e.g., control of cerebral pressure or a severe epileptic seizure).
• In mixed overdoses with benzodiazepines and certain types of antidepressants (so-called tricyclic and tetracyclic antidepressants such as Imipramine, Clomipramine, Mirtazapine, or Mianserina). 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

Talk to your doctor or pharmacist before you start using Flumazenil Hikma.

• The effect of flumazenil is shorter than that of benzodiazepines, and therefore sedation may reappear. It is necessary for you to remain under observation until all the effects of flumazenil have disappeared.
withdrawal symptoms(see section 4).epilepticand have received treatment with benzodiazepines for a long period, the administration of flumazenil is not recommended as it may cause seizures.severe brain injury(e.g., unstable cerebral pressure or severe epileptic seizure), you should be careful as Flumazenil may cause an increase in pressure in your brain.
• Flumazenil is not recommended for the treatment of benzodiazepine addictionor benzodiazepine withdrawal symptoms.
panic attacks or anxiety, Flumazenil may cause new attacks.
• children and infants should only receive Flumazenil to reverse conscious sedation(in which they remain awake). Children should be monitored for at least 2 hours after the administration of Flumazenil.

Using Flumazenil Hikma with other medicines

Tell your doctor if you are using, have recently used, or might use any other medicine.

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

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

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

It is not known whether flumazenil passes into breast milk. Therefore, it is recommended not to breast-feed your child during the 24 hoursafter the administration of flumazenil.

Driving and using machines

For a period of 24 hours after the administration of flumazenil to reverse the sedative effects of benzodiazepines, do not drive, do not use machines, or perform any other physical activity or activity that requires mental concentration, as sedation may reappear.

Flumazenil Hikma contains sodium chloride

This medicine contains 3.7 mg of sodium per ml of solution for injection (18.5 mg/5 ml ampoule or 37 mg/10 ml ampoule). This should be taken into account if you are on a controlled sodium diet.

3. How to use Flumazenil Hikma

Flumazenil Hikma is administered by intravenous injectionor diluted as intravenous infusion(over a longer period).

Flumazenil Hikma should be administered by an anesthesiologist or a doctor with experience. Flumazenil can be used simultaneously with other measures for the recovery of consciousness.

Your doctor will decide the most suitable dose for you. The doses can be very variable and will depend on your particular case. More details are given at the end of the leaflet for healthcare professionals.

In 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 can be injected and repeated at 60-second intervals if the required level of consciousness has not been achieved within 60 seconds, up to a maximum dose of 1.0 mg. The usual dose required is between 0.3 and 0.6 mg, but individual requirements may vary considerably, depending on the duration of the effect of the administered benzodiazepine and the characteristics of the patient.

In intensive care units

The recommended initial dose is 0.3 mg administered intravenously. If after 60 seconds the desired level of consciousness is not achieved, an additional dose of 0.1 mg can be injected and repeated at 60-second intervals, up to a total dose of 2 mg or until the patient wakes up. If drowsiness reappears, an 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.

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 in children under 1 year if the potential benefitsto the patient outweigh the possible risks.

Children over 1 year

To eliminate sedation produced 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 recovered after 45 seconds, new injections of 10 micrograms/kg (up to 200 micrograms) can be administered at 60-second intervals (up to a maximum of 4 times) until a maximum total dose of 50 micrograms/kg or 1 mg, whichever is lower. 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 further questions on the use of this medicine, ask your doctor.

Patients with liver dysfunction

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

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

• anxiety
• fear
• awareness of your heartbeat (palpitations)

Frequency not known (cannot be estimated from the available data)

• hypersensitivity reactions (allergic reactions), including severe 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 when waking up from the effect of benzodiazepines
• flushing of the face and neck
• chills (after rapid injection, no treatment was required)

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

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

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

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Flumazenil Hikma

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

Do not use this medicine after the expiry date which is stated on the label and carton. The expiry date is the last day of the month stated.

Do not store above 25°C.

This medicine is for single use only and should be used immediately after opening.

After dilution, it should not be refrigerated. Chemical and physical stability has been demonstrated for 24 hours at 25°C. From a microbiological point of view, the product should be used immediately, unless the dilution method prevents the risk of microbial contamination. If not used immediately, the in-use storage time and conditions are the responsibility of the user.

Do not use Flumazenil Hikma if the solution is not clear and free of particles.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Contents and Additional Information

Composition of Flumazenil Hikma

The active ingredient is flumazenil.

Each ml of solution contains 0.1 mg of flumazenil.

Each 5 ml ampoule contains 0.5 mg of flumazenil.

Each 10 ml ampoule contains 1.0 mg of flumazenil.

The other componentsare

• disodium edetate
• 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 Container Contents

Flumazenil Hikma is a clear and colorless solution for injection or for dilution before perfusion.

Flumazenil Hikma is packaged in clear glass ampoules.

It is available in the following formats:

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

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

Not all pack 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]

Manufacturer

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.

For further information about this medicinal product, please contact 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 medicinal product is authorized in the Member States of the European Economic Area under the following names:

Date of the last revision of thisleaflet:November 2017

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This information is intended only for healthcare professionals:

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

Flumazenil can be administered as an injection or as a perfusion (For instructions on diluting the medicinal product before administration, see the next chapter).

Flumazenil can be used concomitantly with other resuscitation measures.

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

In case repeated doses do not produce a clear effect on the level of 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 been completely reversed.

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

How to Store Flumazenil Hikma

When flumazenil is used in the form of perfusion, it should be diluted beforehand. Flumazenil should only be diluted with sodium chloride 9 mg/ml (0.9% p/v) solution or glucose 50 mg/ml (5% p/v) solution. The compatibility between flumazenil and 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 storage time and conditions before use are the responsibility of the user. Do not refrigerate. The chemical and physical stability of the specialty has been demonstrated for 24 hours at 25°C.

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

Recommended Doses for Flumazenil Hikma

Adults:

Anesthesia

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

Intensive Care

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

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

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

In case repeated doses do not produce a clear effect on the level of consciousness and respiratory function, it should be considered that the intoxication is not due to benzodiazepines.

The perfusion should be stopped every 6 hours to verify 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 dose of flumazenil should be assessed individually and the injection should be administered slowly.

Elderly Population

There are no data on the use of flumazenil in elderly patients, but it should be noted that this population is generally more sensitive to the effects of medicinal products, and therefore should be treated with due 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, a new injection of 10 micrograms/kg (up to 200 micrograms) can be administered and if necessary repeated at 60-second intervals (up to a maximum of 4 times) until a maximum total dose of 50 micrograms/kg or 1 mg, whichever is lower. The dose should be individualized based on the patient's response. There are no data on the safety and efficacy of repeated administration of flumazenil in children for resedation.

Children under 1 year of age

There are insufficient data on the use of flumazenil in children under 1 year of age. Therefore, flumazenil should only be administered in children under 1 year of age if the potential benefits to the patient outweigh the possible risk.

Patients with Hepatic or Renal Impairment

As flumazenil is mainly metabolized in the liver, careful assessment of the dose is recommended in patients with altered hepatic function. No dose adjustments are required in patients with renal impairment.