Flumazenil 100 Micrograms/Ml Solution For Injection Or Infusion

Package leaflet: Information for the user

Flumazenil 100 micrograms/ml solution for injection or infusion

Flumazenil

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

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

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

- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

This medicine will be always administered to you by an anaesthetist or experienced physician.

What is in this leaflet:

1. What Flumazenil 100 micrograms/ml solution for injection or infusion is and what it is used for

2. What you need to know before you receive Flumazenil 100 micrograms/ml solution for injection or infusion.

3. How you will receive Flumazenil 100 micrograms/ml solution for injection or infusion

4. Possible side effects

5. How to store Flumazenil 100 micrograms/ml solution for injection or infusion

6. Contents of the pack and other information

1. What Flumenazil 100 micrograms/ml solution for injection or infusion is and what it is used for

Flumazenil 100 micrograms/ml solution for injection or infusion contains the active ingredient called Flumazenil.

Flumazenil 100 micrograms/ml solution for injection or infusion is a counteragent (antidote) for the complete or partial reversal of the central sedative effects of benzodiazepines (a specific group of medicines with sedative, sleep inducing, muscle relaxing and antianxiety 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 100 micrograms/ml solution for injection or infusion 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.

You will not receive Flumazenil 100 micrograms/ml solution for injection or infusion

• if you are allergic to flumazenil or any of the other ingredients of this medicine (listed in section 6).

• if benzodiazepines have been given to you to control a life-threatening condition (for example control of pressure in the brain or a serious epileptic fit).

• if you have taken too much of a benzodiazepine along with other medicines such as tricyclic and/or tetracyclic antidepressants (for example Imipramine, Clomipramine, Mirtazepine or Mianserin). Harmful effects of these other antidepressants may not be seen if you are also using benzodiazepines. If you have signs of overdose with other antidepressants, you must not receive Flumazenil 100 micrograms/ml solution for injection or infusion.

You must not be given Flumazenil 100 micrograms/ml solution for injection or infusion if any of the above applies to you. If you are not sure, talk to your doctor or nurse before receiving Flumazenil 100 micrograms/ml solution for injection or infusion.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before receiving Flumazenil 100 micrograms/ml solution for injection or infusion if any of the following apply to you:.

• 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.

• 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 closely observed, possibly in the intensive care unit 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 been treated for long periods with high doses of benzodiazepines, the advantages of the use of Flumazenil should be 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 have epilepsy and have been taking benzodiazepines for a long period of time Flumazenil 100 micrograms/ml solution for injection or infusion can cause fits (convulsions).

• If you have a serious brain injury (for example pressure in the brain or a serious epileptic fit) because Flumazenil 100 micrograms/ml solution for injection or infusion can increase the pressure in the brain.

• If you are dependent (rely) on benzodiazepines or if you have benzodiazepine withdrawal symptoms, you should not receive Flumazenil 100 micrograms/ml solution for injection or infusion.

• If you have had panic or anxiety attacks in the past, Flumazenil 100 micrograms/ml solution for injection or infusion can cause new attacks.

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

• Children and infants should only receive Flumazenil 100 micrograms/ml solution for injection or infusion to reverse conscious sedation (where they remain awake). Children should be closely observed for at least 2 hours after receiving Flumazenil 100 micrograms/ml solution for injection or infusion. There are insufficient data for any other indications. The same applies for children below the age of 1 year.

Other medicines and Flumazenil 100 micrograms/ml solution for injection or infusion

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Flumazenil can alter the effect of medicines with a similar mechanism of action like zopiclone or triazolopyridazine (medicines used to help you sleep).

Harmful effects of other medicines (especially tricyclic antidepressants like Imipramine) may worsen when the effects of benzodiazepines are treated with Flumazenil 100 micrograms/ml solution for injection or infusion.

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 receiving this medicine.

Because of insufficient experience with the use of flumazenil during pregnancy Flumazenil 100 micrograms/ml solution for injection or infusion 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 you received Flumazenil 100 micrograms/ml solution for injection or infusion.

Driving and using machines

After you have received Flumazenil 100 micrograms/ml solution for injection or infusion the effects of benzodiazepines can come back. You must not drive a car, operate machinery or do strenuous (energetic) activity for at least 24 hours after your treatment with Flumazenil 100 micrograms/ml solution for injection or infusion.

Flumazenil 100 micrograms/ml solution for injection or infusion contains sodium

This medicine contains 3.6 mg sodium per ml (18 mg per 5 ml vial) solution for injection. You should take this into consideration and inform your doctor or anaesthetist if you are on a controlled sodium diet. .

Flumazenil 100 micrograms/ml solution for injection or infusion is administered as an intravenous (into a vein) injection or may be diluted for infusion (injection over a longer period).

Flumazenil 100 micrograms/ml solution for injection or infusion will be given by your anaesthetist 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 your need. It depends on the circumstances and must be decided case by case. More details for healthcare professionals are given at the end of the package leaflet.

Use in anaesthesia

The recommended starting dose for adults is 200 micrograms given by slow injection into a vein over 15 seconds. If the required level of consciousness is not obtained after 60 seconds, a further dose of 100 micrograms can be given. This dose can be repeated every 60 seconds until the desired level of consciousness is achieved, up to a maximum total dose of 1 mg. The usual dose is 300-600 micrograms .

Use in intensive care situations

- If you become drowsy again you may be given a slow, continuous injection (infusion) into a vein at a rate of 100-400 micrograms per hour until the correct level of consciousness is achieved.

- If after repeated doses there is no marked improvement in consciousness or independent breathing, your doctor will probably stop giving Flumazenil 100 micrograms/ml solution for injection or infusion and use another method to raise your level of consciousness.

Use in children above the age of 1 year

In case of children above 1 year of age, the starting dose is 10 micrograms/kg body weight (up to 200 micrograms) administered intravenously over a period of 15 seconds. This dose can be repeated, if after a waiting period of 45 seconds the required level of consciousness is not obtained: a follow-up injection of 10 micrograms/Kg (up to 200 micrograms) may be administered.

Where necessary repeated injections at 60-second intervals (up to a maximum of 4 times) to a maximum dose of 50 micrograms/kg or 1 mg, depending on which is the lowest dose can be injected.

Use in children under the age of 1 year

There is little information on the use of flumazenil in children less than 1 year old. Children of less than 1 year old should only be given Flumazenil 100 micrograms/ml solution for injection or infusion if the benefits are expected to be greater than the risk.

If you have any further questions, ask your doctor.

Patients with liver problems

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

Patients with kidney problems

No dose adjustment is required in patients with impaired kidney function.

If you are given more Flumazenil 100 micrograms/ml solution for injection or infusion than you should

If you think you have been given too much Flumazenil 100 micrograms/ml solution for injection or infusion, you should feel no ill effects, however, it would be wise to contact your doctor, pharmacist or hospital as quickly as possible.

If you are stopped being given Flumazenil 100 micrograms/ml solution for injection or infusion

Flumazenil 100 micrograms/ml solution for injection or infusion treatment ends when you become fully conscious. However, because the effects of Flumazenil 100 micrograms/ml solution for injection or infusion may wear off quickly and you may need repeat doses, you should remain under close medical supervision until all drowsiness has subsided.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them. Possible side effects include:

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

• Feeling sick (nausea)

Common (may affect up to 1 in 10 people)

• 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 (may affect up to 1 in 100 people)

• 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 100 micrograms/ml solution for injection or infusion can cause withdrawal symptoms such as:

• tension

• panic (agitation)

• anxiety

• confusion

• abnormal sensory perceptions (hearing voices, seeing things that are not there, sensations on the skin)

• shaking (tremor)

• fits (convulsions)

Additional side effects in children

Similar effects listed above can be seen in children. When Flumazenil 100 micrograms/ml solution for injection or infusion has been used in children abnormal crying, agitation and aggressive reactions have been reported.

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

5. How to store Flumazenil 100 micrograms/ml solution for injection or infusion

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 after EXP. The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

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 time and conditions prior to use are the responsibility of the user and would not be longer than 24 hours at 2 to 8°C.

Single use only. After first opening the medicinal product should be used immediately.

Discard any unused portion. 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.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

6. Content of the pack and other information

What Flumazenil 100 micrograms/ml solution for injection or infusion contains

The active substance is flumazenil.

Each ml of solution for injection or infusion contains 100 micrograms of flumazenil.

The other ingredients are

• sodium chloride

• disodium edetate

• glacial acetic acid

• hydrochloric acid (for pH adjustment)

• sodium hydroxide (for pH adjustment)

• water for injections

What Flumazenil 100 micrograms/ml solution for injection or infusion looks like and content of the pack

The solution is a clear and colorless solution free from visible particles.

It is filled into Type I colourless tubular vial with grey bromo butyl omniflex coated rubber stopper and flip off aluminium seal.

Flumazenil 100 micrograms/ml solution for injection or infusion is available in pack sizes of:

1 x 5 ml vial,

5 x 5 ml vial,

6 x 5 ml vial,

10 x 5 ml vial,

12 x 5 ml vial,

25 x 5 ml vial

Not all pack sizes may be marketed

Marketing Authorization Holder and Manufacturer:

Marketing Authorisation Holder

Mylan

Potters Bar, Hertfordshire, EN6 1TL, United Kingdom Manufacturer

Agila Specialties Polska Sp.z.o.o 10, Daniszewska Str,

03-230 Warsaw, Poland

The leaflet was last revised in 09/2014.

The following information is intended for healthcare professionals only.

Flumazenil 100 micrograms/ml solution for injection or infusion

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 the 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 100 micrograms/ml solution for injection or infusion, the possibility should be considered that the intoxication is due to agents other than benzodiazepines.

If Flumazenil 100 micrograms/ml solution for injection or infusion 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 100 micrograms/ml solution for injection or infusion 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.

How to store Flumazenil 100 micrograms/ml solution for injection or infusion

When Flumazenil 100 micrograms/ml solution for injection or infusion 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.

This medicinal product does not require any special storage conditions.

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

From a microbiological perspective, the diluted Flumazenil 100 micrograms/ml solution for injection or infusion should be used immediately. If not used immediately, the in-use storage should not be longer than 24 hours at 2 to 8°C.

Flumazenil 100 micrograms/ml solution for injection or infusion must not be mixed with other medicinal products except for those mentioned above.

The recommended doses for Flumazenil 100 micrograms/ml solution for injection or infusion

Adults

Anaesthesia

The recommended starting dose is 200 micrograms administered intravenously over 15 seconds. If the required level of consciousness is not obtained within 60 seconds, a further dose of 100 micrograms can be injected and repeated at 60-second intervals, up to a maximum dose of 1.0 mg. The usual dose required lies between 300 and 600 micrograms, but may deviate depending on the patient’s characteristics and the benzodiazepine used.

Intensive care

If drowsiness recurs, an intravenous infusion of 100 micrograms - 400 micrograms per hour 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 re-sedation 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.

Children above 1 year of age

For the reversal of conscious sedation induced with benzodiazepines in children > 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 obtained after waiting an additional 45 seconds, further injection of 10 micrograms/kg may be administered (up to 200 micrograms) and repeated at 60 second intervals where necessary (a maximum of 4 times) to a maximum total dose of 50 micrograms/kg or 1 mg, whichever is lower. The dose should be individualised based on the patient's response. No data are available on the safety and efficacy of repeated administration of flumazenil to children for re-sedation.

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.

Elderly

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

Patients with renal and 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.