0,5 mm 9 mm 1,5 mm

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PACKAGE LEAFLET: INFORMATION FOR THE USER

Read all of this leaflet carefully before you start using this medicine

-    Keep this leaflet. You may need to read it again.

-    If you have any further questions, ask your doctor or pharmacist.

-    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

-    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet

1.    What Flumazenil is and what it is used for

2.    Before Flumazenil is given to you

3.    How to use Flumazenil

4.    Possible side effects

5.    How to store Flumazenil

6.    Further information

1.    WHAT FLUMAZENIL IS AND WHAT IT IS USED FOR

Flumazenil is a counteragent (antidote) for the complete or partial reversal of the central sedative effects of benzodiazepines (specific group with sedative, sleep inducing, muscle relaxing and anxiolytic properties).

It may therefore be used in anaesthesia to wake you up after certain diagnostic tests or in intensive care if you have been hold under sedative conditions. Flumazenil may also be used for treatment of intoxications or overdose with benzodiazepines.

2.    BEFORE FLUMAZENIL IS GIVEN TO YOU

Do not use Flumazenil

•    if you are allergic (hypersensitive) to flumazenil or any of the other ingredients (see Section 6 for a list of other ingredients).

•    if benzodiazepines have been given to you to control a life-threatening condition (e.g. pressure on the brain or a serious epileptic fit).

•    if you have taken too much of a benzodiazepine with other medicines such as tricyclic and/or tetracyclic antidepressants (e.g. Imipramin, Clomipramin, Mirtazepine or Mianserin). Harmful effects of these other antidepressants may not be seen if benzodiazepines are also being used. If you have signs of overdose with other antidepressants, Flumazenil must not be used.

Take special care with Flumazenil

•    the effects of flumazenil usually wear off more quickly than those of benzodiazepines. This means that the relaxing effects of the benzodiazepines can come back. You will be checked until the effects of flumazenil have worn off.

•    if you have taken benzodiazepines for a long time flumazenil can cause withdrawal symptoms (see Section 4 for details).

•    if you have epilepsy and have been taking benzodiazepines for a long period of time Flumazenil can cause fits (convulsions).

•    if you have a serious brain injury (e.g. pressure on the brain or a serious epileptic fit) because Flumazenil can increase the pressure on the brain.

•    if you are dependent (rely) on benzodiazepines or if you have benzodiazepine withdrawal symptoms. You should not use Flumazenil in these cases.

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The following information is intended for medical or healthcare professionals only:

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

Flumazenil may be administered as injection or as infusion (for instructions on dilution of the product before administration, see chapter below). Flumazenil may be used concomitantly with other resuscitative measures. This medicinal product is for single use only. It should be inspected visually prior to use and should only be used if the solution is clear and practically free from particles.

If no clear effect on awareness and respiration is obtained after repeated dosing with Flumazenil, the possibility should be considered that the intoxication is due to agents other than benzodiazepines.

If Flumazenil is used in anaesthesiology at the end of surgery, it should not be given until the effects of the muscle relaxants have been fully reversed.

Children who have been sedated with Midazolam should be closely observed for at least 2 hours after Flumazenil administration, in case repeated sedation or difficulty with breathing occurs. When other benzodiazepines have been used the monitoring time must be adjusted based on how long their effects last.

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•    if you have had panic or anxiety attacks in the past, Flumazenil can cause new attacks.

•    if you are dependent (rely on) on alcohol or some other medicines. There is a risk of you becoming benzodiazepine tolerant (where you no longer get any benefit) or benzodiazepine dependent.

•    children and infants should only receive Flumazenil to reverse conscious sedation (where they remain awake). Children should be closely observed for at least 2 hours after receiving Flumazenil.

Taking other medicines

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Harmful effects of other medicines (especially tricyclic antidepressants like Imipramin) may worsen when the effects of benzodiazepines are treated with Flumazenil.

Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine.

Because of insufficient experience during pregnancy flumazenil should only be used if the advantage for you is higher than the potential risk for the unborn baby. The administration of flumazenil during pregnancy is not contraindicated in an emergency situation.

It is not known whether flumazenil is excreted in breast milk. Therefore it is recommended not to breast-feed 24 hours after administration of Flumazenil.

Driving and using machines

After you have received Flumazenil the effects of benzodiazepines can come back. You must not drive a car, operate machinery or do strenuous activity for at least 24 hours after Flumazenil treatment.

Important information about some of the ingredients of Flumazenil

This medicinal product contains 3.7 mg sodium per ml (18.5 mg / 5 ml ampoule size or 37 mg / 10 ml ampoule size) solution for injection. To be taken into consideration if you are on a controlled sodium diet.

3. HOW TO USE FLUMAZENIL

Flumazenil is administered as an intravenous (into a vein) injection or may be diluted for infusion (injection over a longer period).

Flumazenil will be given by your anesthetist or an experienced physician. It may be used with other treatments given to revive (resuscitate) you.

This medicinal product is for single use only. Any unused medicine should be thrown away. The solution should be inspected before use. It should only be used if it is clear, colourless and free from particles.

The dose will be defined by your doctor according to the need. It depends from the circumstances and must be decided case by case. More details for healthcare professionals are given at the end of the package leaflet.

Children under the age of 1 year

There is little information on the use of Flumazenil in children less than 1

How to store Flumazenil

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

From a microbiological perspective, the diluted Flumazenil should be used immediately. If not used immediately, the in-use storage should not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

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

The recommended doses for Flumazenil

Adults:

Anaesthesia

The recommended starting dose is 0.2 mg administered intravenously over 15 seconds. If the required level of consciousness is not obtained within 60 seconds, a further dose of 0.1 mg can be injected and repeated at 60-second intervals, up to a maximum dose of 1.0 mg. The usual dose required lies between 0.3 and 0.6 mg, but may deviate depending on the patient's characteristics and the benzodiazepine used.

year old. Children of less than 1 year old should only be given Flumazenil if the benefits are expected to be greater than the risk.

If you have any further questions on the use of Flumazenil, ask your doctor.

Patients with hepatic (liver) impairment

In patients with impaired liver function, the dosing must be managed carefully.

4. POSSIBLE SIDE EFFECTS

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

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

Very common (in more than 1 in 10 patients)

•    Feeling sick (nausea)

Common (1 - 10 in 100 patients)

•    hypersensitivity (allergic reaction)

•    anxiety

•    mood swings (emotional lability)

•    difficulty sleeping (insomnia)

•    sleepiness (somnolence)

•    dizziness

•    headache

•    panic (agitation)

•    shaking (tremor)

•    dry mouth

•    rapid breathing (hyperventilation)

•    speech disorder

•    tingling or numbness of the hands or feet (paraesthesia)

•    double vision (diplopia)

•    squinting (strabismus)

•    watering eyes (lacrimation)

•    feeling your heartbeat (palpitations)

•    flushing

•    low blood pressure on standing (orthostatic hypotension)

•    high blood pressure on waking from the effects of benzodiazepines

•    vomiting

•    hiccups

•    sweating

•    fatigue

•    injection site pain

Uncommon (1 - 10 in 1,000 patients)

•    fits (convulsions)

•    abnormal hearing

•    irregular heartbeat

•    difficulty breathing

•    cough

•    blocked nose (nasal congestion)

•    chest pain

•    shivering

If you have been treated with benzodiazepines for a long time, Flumazenil can cause withdrawal symptoms such as:

•    tension

•    panic (agitation)

•    anxiety

•    confusion

•    abnormal sensory perceptions (hearing voices, seeing things that aren't there, sensations on the skin)

•    shaking (tremor)

•    fits (convulsions)

Similar effects can be seen in children. When Flumazenil has been used in children

abnormal crying, agitation and aggressive reactions have been reported.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5.    HOW TO STORE FLUMAZENIL

Keep out of the reach and sight of children.

Flumazenil must not be used after the expiry date which is stated on the label and carton. The expiry date refers to the last day of that month.

Do not store above 25°C.

This medicine is for single use only and should be used immediately after opening. If diluted, Flumazenil should not be stored for longer than 24 hours at 2-8°C.

Flumazenil should only be used if the solution is clear and free from particles.

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

6.    FURTHER INFORMATION

What Flumazenil contains

The active substance is flumazenil.

Each ml of solution for injection contains 0.1 mg flumazenil.

Each 5 ml ampoule contains 0.5 mg flumazenil.

Each 10 ml ampoule contains 1.0 mg flumazenil.

The other ingredients are

•    disodium edetate

•    glacial acetic acid

•    sodium chloride (3.7 mg per ml)

•    hydrochloric acid 36% for pH adjustment

•    sodium hydroxide for pH adjustment

•    water for injections

What Flumazenil looks like and contents of the pack

Flumazenil is a clear and colourless solution for injection, or for dilution before infusion. Flumazenil comes in colourless glass ampoules.

Following pack sizes are available:

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

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Hikma Farmaceutica (Portugal), S.A.

Estrada do Rio da Mo, 8, 8A e 8B - Fervenpa 2705-906 Terrugem SNT - Portugal

This medicinal product is authorised in the Member State of the EEA under the following names:

Austria    Flumazenil 0,1 mg/ml Injektionslosung und Konzentrat

zur Herstellung einer Infusionslosung

Germany    Flumazenil 0,1 mg/ml Injektionslosung und Konzentrat

zur Herstellung einer Infusionslosung Italy    Flumazenil Hikma 0,1 mg/ml soluzione

iniettabile/concentrato per soluzione per infusione Portugal    Flumazenilo Hikma 0,1 mg/ml solupao

injectavel/concentrado para solupao para perfusao United Kingdom Flumazenil 0.1 mg/ml solution for

injection / concentrate for solution for infusion

This leaflet was last approved in 05/2010.

Intensive Care

The recommended starting dose is 0.2 mg administered intravenously over 15 seconds. If the required level of consciousness is not obtained within 60 seconds, a further 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 awakes. If drowsiness recurs, an intravenous infusion of 0.1 - 0.4 mg/h may be useful. The rate of infusion should be adjusted individually to achieve the desired level of consciousness.

If no clear effect on awareness and respiration is obtained after repeated dosing, it should be considered that the intoxication is not due to benzodiazepines.

Infusion should be discontinued every 6 hours to verify whether resedation occurs.

To avoid withdrawal symptoms in patients treated for a long period of time with high doses of benzodiazepines in the intensive care unit, the dosage of flumazenil has to be titrated individually and the injection has to be administered slowly.

Elderly

In the absence of data on the use of flumazenil in elderly patients, it should be noted that this population is generally more sensitive to the effects of medicinal products and should be treated with due caution.

Children and adolescents (from 1 to 17 years)

For the reversal of conscious sedation induced by benzodiazepines in children older than 1 year the recommended starting dose is 0.01 mg/kg (up to 0.2 mg), administered intravenously over a period of 15 seconds. If, after a waiting period of 45 seconds, the required level of consciousness is not obtained a follow-up injection of 0.01 mg/kg (up to 0.2 mg) may be administered and where necessary repeated at 60-second intervals (up to a maximum of 4 times) to a maximum dose of 0.05 mg/kg or 1 mg, depending on which is the lowest dose. The dose should be adjusted to the patient's response. There are no data on safety and efficacy of repeated flumazenil administration in children in case of resedation.

Children under the age of 1 year

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

Patients with renal or hepatic impairment In patients with impaired hepatic function, the elimination of flumazenil may be delayed (see section 5.2) and therefore careful titration of dosage is recommended. No dosage adjustments are required in patients with renal impairment.