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FLUMAZENIL 0.1 MG/ML SOLUTION FOR INJECTION / INFUSION

Active substance(s): FLUMAZENIL / FLUMAZENIL / FLUMAZENIL

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PACKAGE LEAFLET: INFORMATION FOR THE USER

Flumazenil 0.1 mg/ml
solution for injection/infusion
flumazenil

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.
• 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.
What is in this leaflet
1. What Flumazenil is and what it is used for
2. What you need to know before you use Flumazenil
3. How to use Flumazenil
4. Possible side effects
5. How to store Flumazenil
6. Contents of the pack and 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. WHAT YOU NEED TO KNOW BEFORE YOU USE
FLUMAZENIL
Do not use Flumazenil
• if you are allergic to flumazenil or any of the other ingredients (listed
in Section 6).
• if benzodiazepines have been given to you to control a lifethreatening 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.
Warnings and precautions
Talk to your doctor or pharmacist before using 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 liver problems.
• 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.
• 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.
Other medicines and Flumazenil
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 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.
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 200micrograms) and
repeated at 60 second intervals where necessary (a maximum of 4
times) to maximum total dose of 50 micrograms/kg or 1mg, whichever

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.

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.

is lower. The dose should be individualised based on the patient’s
response. No data available on the safety and efficacy of repeated
administration of flumazenil to children for re-sedation.
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, this medicine 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)
• fear
• fits (convulsions)
• abnormal hearing
• irregular heartbeat
• difficulty breathing
• cough
• blocked nose (nasal congestion)
• chest pain
• shivering
Unknown
• severe allergic reaction
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.
Reporting of side effects
If you get any side effects, talk to your doctor or nurse.
This includes any possible side effects not listed in this leaflet. You can
also report side effects directly via the national reporting system listed
in: Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard
By reporting side effects you can help provide more information on
the safety of this medicine.

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 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.
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 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 Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó, 8, 8A e 8B - Fervença
2705-906 Terrugem SNT, Portugal
Tel.: +351 219 608 410
Fax: +351 219 615 102
e-mail: geral@hikma.pt
Manufacturer
Hikma Italia SpA
Viale Certosa, 10, 27100 Pavia, Italy
Distributed by:
Consilient Health (UK) Ltd.
No.1 Church Road, Richmond upon Thames, Surrey, TW9 2QE
This leaflet was last revised in May 2017.

P0445

Intensive Care
The recommended initial dose of Flumazenil is 0.3 mg i.v. 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.

Paediatric population
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
10micrograms/kg may be administered (up to 200micrograms) and
repeated at 60 second intervals where necessary (a maximum of 4
times) to maximum total dose of 50 micrograms/kg or 1mg, whichever
is lower. The dose should be individualised based on the patient’s
response. No data 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.
Patients with renal or hepatic impairment
Since flumazenil is primarily metabolized in the liver, careful titration
of dosage is recommended in patients with impaired hepatic function.
No dosage adjustments are required in patients with renal impairment.

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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