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

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Flumazenil Hikma 0.1 mg/ml solution for injection and infusion concentrate 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 questions, ask your doctor or pharmacist.

• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Leaflet contents

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

2. What you need to know before using Flumazenil Hikma

3. How to use Flumazenil Hikma

4. Possible side effects

5. Storage of Flumazenil Hikma

6. Contents of the pack and other information

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

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

Therefore, it should be used in anesthesia to awaken patients after certain diagnostic procedures or in intensive care when sedation has been maintained. Flumazenil Hikma may also be used to treat benzodiazepine poisoning or overdosage, as well as to counteract paradoxical reactions caused by benzodiazepines.

Flumazenil Hikma can also be used as a diagnostic measure in cases of unconsciousness of unknown origin.

2. What you need to know before using Flumazenil Hikma

Do not use Flumazenil Hikma:

• if you are allergic to the active substance or to any of the other components of this medicine (listed in section 6).
• if benzodiazepines have been administered to manage a life-threatening condition (e.g. control of intracranial pressure or a severe epileptic seizure).
• in mixed intoxications involving benzodiazepines and certain types of antidepressants (so-called tricyclic and tetracyclic antidepressants such as Imipramine, Clomipramine, Mirtazepine or Mianserin). The toxicity of these antidepressants may be masked by the protective effects of benzodiazepines. If you show symptoms of an overdose of these antidepressants, Flumazenil Hikma must not be used to reverse the effects of benzodiazepines.

Warnings and precautions

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

• the effect of flumazenil is shorter than that of benzodiazepines, and therefore sedation may recur. Therefore, you must remain under observation until all effects of flumazenil have completely disappeared.
• if you have liver problems.
• if you have received long-term treatment with benzodiazepines, flumazenil may cause withdrawal symptoms (see section 4).
• if you are epileptic and have received long-term benzodiazepine treatment, administration of flumazenil is not recommended, as it may trigger seizures.
• if you have a severe brain injury (e.g. unstable intracranial pressure or severe epileptic convulsions), you must be cautious, as flumazenil may cause an increase in intracranial pressure.
• flumazenil is not recommended for the treatment of benzodiazepine dependence or benzodiazepine withdrawal symptoms.
• if you have previously experienced panic attacks or anxiety, flumazenil may provoke new episodes.
• if you are dependent on alcohol or medications, as you have an increased risk of tolerance (lack of beneficial effects) and benzodiazepine dependence.
• children and infants should receive flumazenil only to reverse conscious sedation (in which they remain awake). Children must be monitored for at least 2 hours after administration of flumazenil.

Using Flumazenil Hikma with other medicines

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines.

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

Pregnancy and breastfeeding

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

Due to lack of experience during pregnancy, Flumazenil Hikma should only be used if the benefit to you outweighs the potential risk to the unborn child. Administration of flumazenil during pregnancy is not contraindicated in emergency situations.

It is not known whether flumazenil passes into breast milk. Therefore, breastfeeding is not recommended for 24 hours after administration of flumazenil.

Driving and using machines

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

Flumazenil Hikma contains sodium chloride

This medicine contains 3.7 mg of sodium per ml of injectable solution (18.5 mg per 5 ml ampoule or 37 mg per 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 injection (into the vein) or diluted as an intravenous infusion (over a longer period).

Flumazenil Hikma must be administered by an anaesthetist or a physician experienced in its use. Flumazenil may be used simultaneously with other measures to restore consciousness.

Your doctor will decide the most appropriate dose for you. Doses may vary widely and depend on your individual condition. Further details for healthcare professionals are provided at the end of the leaflet.

In anaesthesia

The recommended initial dose is 0.2 mg i.v., administered over 15 seconds. An additional dose of 0.1 mg may 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 action of the administered benzodiazepine and patient characteristics.

In intensive care units

The recommended initial dose is 0.3 mg administered intravenously. If the desired level of consciousness is not achieved within 60 seconds, an additional dose of 0.1 mg may be injected and repeated at 60-second intervals, up to a total dose of 2 mg or until the patient awakens. If drowsiness recurs, an intravenous infusion of 0.1–0.4 mg/h may be useful. The infusion rate should be individually adjusted to achieve the desired level of consciousness.

Children under 1 year of age

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

Children over 1 year of age

To reverse benzodiazepine-induced sedation 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 consciousness is not restored within 45 seconds, further injections of 10 micrograms/kg (up to 200 micrograms) may be given as needed every 60 seconds (up to a maximum of 4 times), up to a total maximum 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 resedation.

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

Patients with hepatic impairment (liver)

In patients with impaired liver function, elimination of flumazenil may be delayed; therefore, careful dose adjustment is recommended.

4. Possible adverse effects

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

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

Frequent (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
• 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 hepatic impairment, mainly after long-term treatment with benzodiazepines or multiple drug abuse
• transient increase in blood pressure upon awakening from the effects of benzodiazepines
• redness of the face and neck
• chills (after rapid injection, have not required treatment)

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

• agitation
• anxiety
• emotional lability
• confusion
• sensory distortions (hearing voices, seeing things that are not there, sensations on the skin)

Adverse effects in children do not differ greatly from those in adults. When flumazenil is used in children, abnormal crying, restlessness, and aggressive reactions have been observed.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it involves possible adverse effects not listed in this leaflet. You may also report them directly through the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Flumazenil Hikma Storage

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

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

Do not store above 25°C.

This medicine is for single use only 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 the risk of microbial contamination. If not used immediately, the storage duration and conditions prior to use are the responsibility of the user.

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

Medicines must not be disposed of via wastewater or household waste. If you are unsure how to dispose of unused medicines or their packaging, consult your pharmacist. This will help protect the environment.

6. Contents of the container and additional information

Composition of Flumazenil Hikma

The active substance is flumazenil.

Each ml of solution contains 0.1 mg of flumazenil.

Each 5 ml vial contains 0.5 mg of flumazenil.

Each 10 ml vial 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 injections

Appearance of the product and contents of the container

Flumazenil Hikma is a clear, colourless solution for injection or for dilution prior to infusion.

Flumazenil Hikma is packaged in colourless glass vials.

It is available in the following pack sizes:

Carton boxes containing 5 or 50 (10x5) vials with 5 ml of solution.

Carton boxes containing 5 or 50 (10x5) vials with 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

Telephone: +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 this leaflet: November 2017

------------------------------------------------------------------------------------------------------------------?

This information is intended for healthcare professionals only:

Flumazenil must be administered intravenously by an anaesthetist or experienced physician.

Flumazenil may be given as an injection or by infusion (for dilution instructions prior to administration, see the following section).

Flumazenil may be used concomitantly with other resuscitation measures.

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

If no clear improvement in level of consciousness and respiratory function is observed after repeated doses, benzodiazepine overdose should be ruled out.

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

Due to the possible risk of respiratory depression and resedation, children previously sedated with midazolam should be monitored for at least 2 hours after administration of flumazenil. When other benzodiazepines are used, the monitoring period should be adjusted according to the expected duration of action.

How to store Flumazenilo Hikma

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

From a microbiological standpoint, 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 prior to use are the responsibility of the user. Do not refrigerate. Chemical and physical stability of the product has been demonstrated for 24 hours at 25°C.

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

Recommended doses for Flumazenil Hikma

Adults:

Anaesthesia

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

Intensive care

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

If drowsiness recurs, an intravenous infusion of 0.1–0.4 mg/h may be useful.

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

If no clear improvement in level of consciousness and respiratory function is observed after repeated doses, benzodiazepine overdose should be ruled out.

The infusion should be paused every 6 hours to assess whether resedation occurs.

To avoid withdrawal syndrome in patients treated for prolonged periods with high doses of benzodiazepines in intensive care units, the flumazenil dose should be individually assessed and the injection administered slowly.

Elderly population

There are no specific data on the use of flumazenil in elderly patients; however, this population is generally more sensitive to the effects of drugs and should therefore be treated with appropriate caution.

Paediatric population

Children over 1 year of age

To reverse benzodiazepine-induced sedation 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 within an additional 45 seconds, a further injection of 10 micrograms/kg (up to 200 micrograms) may be given, and repeated if necessary at 60-second intervals (up to a maximum of 4 times) to 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 is 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 when the potential benefits outweigh the possible risks.

Patients with hepatic or renal impairment

As flumazenil is primarily metabolized in the liver, careful dose evaluation is recommended in patients with impaired hepatic function. Dose adjustment is not required in patients with renal impairment.