PACKAGE LEAFLET: INFORMATION FOR THE USER

Flumazenil 0.1 mg/ml Solution for Injection

Flumazenil

What is in this leaflet

1.    What Flumazenil is and what it is used for

2.    What you need to know before you use Flumazeni

3.    How to use Flumazenil

4.    Possible side effects

5.    How to store Flumazenil

6.    Contents of the pack and other 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 held under sedative conditions. Flumazenil may also be used for the diagnosis and treatment of intoxications or overdose with benzodiazepines.

Flumazenil Kabi is also used in children (more than 1 year old) to wake them up after they have been given a 'benzodiazepine' medicine to make them sleepy during a medical procedure.

2. What you need to know before you use Flumazeni

Do not use Flumazenil

-    if you are allergic (hypersensitive) to flumazenil or any of the other ingredients (listed in section 6).

-    if benzodiazepines have been administered to you to control a potentially life-threatening situation (for example control of pressure in the brain or a serious epileptic seizure).

-    in mixed intoxications with benzodiazepines and certain types of other antidepressants (so called tricyclic and tetracyclic antidepressants like Imipramine, Clomipramine, Mirtazapine or Mianserin). The toxicity

of these antidepressants can be masked by protective benzodiazepine effects. If you are showing signs of a significant overdose of these antidepressants, Flumazenil must not be used to reverse benzodiazepine effects.

Warnings and precautions

-    If you do not wake up after Flumazenil is administered, another reason for this will be considered because Flumazenil specifically reverses the effects of benzodiazepines.

-    If Flumazenil is administered to you at the end of your operation to wake you up, it should not be given until the effects of muscle relaxants have gone away.

-    As the action of flumazenil is usually shorter than that of benzodiazepines, sedation may possibly recur. You will be closely observed, possibly in the intensive care unit until the effects of flumazenil have gone away.

-    If you have received high dose and/or long-term (chronic) treatment with benzodiazepines, at any time within the weeks preceding flumazenil administration, rapid injection of high doses of flumazenil (more than 1 mg) should be avoided since this may cause withdrawal symptoms (see section

4. Possible side effects).

-    If you have been treated for long periods with high doses of benzodiazepines, the advantages of the use of Flumazenil should be carefully weighed against the risk of withdrawal symptoms.

-    In children previously sedated with midazolam.

These children should be closely observed in intensive care units for at least 2 hours after administration of Flumazenil because repeated sedation or difficulty with breathing can occur. In case of sedation by other benzodiazepines, the monitoring must be adjusted according to their expected duration.

-    If you are epileptic and have received benzodiazepine treatment for a long period of time, the administration of flumazenil is not recommended as flumazenil can cause seizures.

-    Seizures or other toxic effects can be more severe in cases of mixed drug overdose (e.g. intoxication with benzodiazepines and cyclic antidepressents)

-    If you have serious brain injury (and/or instable pressure in your brain) care willl be taken as Flumazenil can cause an increased pressure in your brain.

-    As Flumazenil is not recommended for the treatment of benzodiazepine-dependence or for the treatment of benzodiazepines-withdrawal-symptoms.

-    If you have experienced panic attacks in the past Flumazenil can cause new attacks.

-    If you are dependent on alcohol or medicines as you have a higher risk of benzodiazepine tolerance and dependence.

-    if your liver is not working well flumazenil elimination can be delayed.

Children

-    Children should only receive Flumazenil after deliberate sedation. There are unsufficient data for any other indications. The same applies for children below the age of 1 year

Other medicines and Flumazenil

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

When using Flumazenil in cases of an accidental overdose it has to be taken into account that the toxic effects of other psychotropic medicinal products (especially tricyclic anti-depressants like Imipramine) taken concurrently, may increase with the subsidence of the benzodiazepine effect. Interaction with other central nervous system depressants has not been observed.

Flumazenil with alcohol

There is no known interaction between ethanol and flumazenil.

Pregnancy, breast-feeding and fertility

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 taking this medicine.

Because of insufficient experience during pregnanacy 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 receiving Flumazenil for the reversal of the sedative effects of benzodiazepines you must not drive a car, operate machinery or engage in any other physically or mentally demanding activity for at least 24 hours since sedation may possibly recur.

Flumazenil contains sodium chloride

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 by patients on a controlled sodium diet.

3. How to use Flumazenil

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

Flumazenil will be given by your anaesthetist or experienced physician. Flumazenil may be used at the same time as other resuscitative measures.

This medicinal product is for single use only. Any unused solution should be discarded. The solution should be inspected visually prior to use. It should only be used if the solution is clear, colourless and practically free from particles.

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 (kidney) or hepatic (liver) impairment

In patients with impaired liver function, the elimination of flumazenil may be delayed and therefore careful titration of dosage is recommended.

No dosage adjustments are required in patients with impaired kidney function.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

For information intended for healthcare professionals please see accordant section below.

4. Possible side effects

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

Very common (may affect more than 1 in 10 people) Nausea

Common (may affect up to 1 in 10 people)

hypersensitivity reactions (allergic reactions), anxiety (after rapid injection, not requiring treatment), emotional lability, having problems in initiating and maintaining sleep (insomnia), feeling sleepy (somnolence), vertigo, headache, agitation (after rapid injection, not requiring treatment), unvoluntary trembling or quivering (tremor), dry mouth, abnormal rapid and deep respiration (hyperventilation), speech disorder, subjective cutaneous sensations (e.g. cold, warmth, tingling, pressure, etc.) in the absence of stimulation (paresthesia), double vision, strabismus (squinting), lacrimation (production of tear fluid) increased, heart palpitations (after rapid injection, not requiring treatment), reddening of the skin (flushing), low blood pressure on transition from lying to standing, transient increased blood pressure (on awaking), vomitting, hiccup, sweating, fatigue, injection site pain

V005

M0xxxxx/00 UK

Uncommon (may affect up to 1 in 100 people)

Fear (after rapid injection, not requiring treatment), convulsions (in patients suffering from epilepsy or severe liver insufficiency, mainly after long-term treatment with benzodiazepines or mixed drug overdose (see section 2 warnings and precautions), abnormal hearing, slow or rapid heart rate, premature beat of your heart (extrasystole), difficulty breathing (dyspnoea), cough, nasal congestion, chest pain, shivering (after rapid injection, not requiring treatment)..

Not known (frequency cannot be estimated from the available data)

Withdrawal symptoms (see below); panic attacks (in patients with a history of panic reactions); abnormal crying, agitation, aggressive reactions, flushing

If you were treated for a long period with benzodiazepines flumazenil can induce withdrawal symptoms. The symptoms are: tension, agitation, anxiety, emotional lability, confusion, hallucinations, involuntary trembling or quivering (tremor) and convulsions.

In general the undesirable effects in children do not

differ much from that in adults. When using Flumazenil to awaken a child from sedation, 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.

The other ingredients are disodium edetate, glacial acetic acid, sodium chloride, sodium hydroxide solution 4%, water for injections.

What Flumazenil looks like and contents of the pack

Flumazenil is a clear and colourless solution for injection and concentrate for solution for infusion in colourless glass ampoules.

Following packaging sizes are available:

Carton boxes with 5 or 10 ampoules containing 5 ml solution.

Carton boxes with 5 or 10 ampoules containing 10 ml solution

Not all packaging sizes may be marked.

Marketing Authorisation Holder and Manufacturer

Fresenius Kabi Limited

Cestrian Court, Eastgate Way, Manor Park, Runcorn Cheshire WA7 1NT United Kingdom

Manufacturer:

hameln pharmaceuticals gmbh Langes Feld 13 31789 Hameln Germany

This leaflet was last revised 02/2013

5. How to store Flumazenil

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 refers to the last day of that month.

Do not store above 25°C

This medicinal product is for single use only.

Shelf life after first opening: the medicinal product should be used immediately.

Shelf life after dilution: 24 hours.

Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 °C, unless dilution has taken place in controlled and validated aseptic conditions.

Do not use this medicine if the solution is not clear and free from particles.

Any unused solution should be discarded in accordance with local requirements.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information.

What Flumazenil contains The active substance is flumazenil.

Each millilitre contains 0.1 mg = 100 micrograms flumazenil. Each ampoule with 5 ml contains 0.5 mg = 500 micrograms flumazenil.

Each ampoule with 10 ml contains 1.0 mg = 1000 micrograms flumazenil.

FRESENIUS

KABI

The following information is intended for healthcare professionals only:

Detailed storage conditions can be found in section 5. How to store Flumazenil.

When Flumazenil is to be used in infusion, it must be diluted prior to infusion. Flumazenil should only be diluted with sodium chloride 9 mg/ml (0.9% w/v) solution, glucose 50 mg/ml (5% w/v) or sodium chloride 4.5 mg/ml (0.45% w/v) + glucose 25 mg/ml (2.5% w/v) solution. Compatibility between flumazenil and other solutions for injection has not been established.

This medicinal product must not be mixed with other medicinal products except for those mentioned in this section.

For further information on dosage instructions please see section 3 of the Package Information Leaflet.