Flumazenil Kabi

Package Leaflet: Information for the User

Flumazenil Kabi 0.1 mg/ml Injection Solution

Generic Medicine
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, nurse, or healthcare professional.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, nurse, or healthcare professional. See section 4.

Contents of this leaflet:

1. What Flumazenil Kabi is and what it is used for
2. What you need to know before taking Flumazenil Kabi
3. How to take Flumazenil Kabi
4. Possible side effects
5. How to store Flumazenil Kabi
6. Contents of the pack and other information

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

Flumazenil Kabi is an antagonist (antidote) capable of completely or partially reversing the central sedative effects of benzodiazepines (a specific class with sedative, hypnotic, muscle relaxant, and anxiolytic properties).
Therefore, it can be used in anesthesia to restore consciousness after certain diagnostic procedures, or in intensive care following sedation. Flumazenil can also be used for the diagnosis and treatment of benzodiazepine intoxication or overdose.
Flumazenil Kabi is used in children (over 1 year of age) to reverse sedation induced by benzodiazepines following a medical procedure.

2. What you need to know before taking Flumazenil Kabi

Do NOT use Flumazenil Kabi

• if you are allergic (hypersensitive) to flumazenil or to any of the other ingredients (listed in section 6);
• if you have been administered benzodiazepines to control a potentially life-threatening condition (e.g. to control intracranial pressure or a severe epileptic seizure);
• in mixed intoxications involving benzodiazepines and certain other types of antidepressants (so-called tricyclic and tetracyclic antidepressants such as imipramine, clomipramine, mirtazapine or mianserin). The toxicity of these antidepressants may be masked by the protective effects of benzodiazepines. If you show symptoms of overdose with these antidepressants, do not use Flumazenil Kabi to reverse the effects of benzodiazepines.

Warnings and precautions

• If you do not regain consciousness after administration of Flumazenil Kabi, consider other causes, as Flumazenil Kabi specifically reverses the effects of benzodiazepines.
• If you are given Flumazenil Kabi after a surgical procedure to reverse sedation, it should not be administered until the effects of muscle relaxants have worn off.
• Since the duration of action of flumazenil is normally shorter than that of benzodiazepines, sedative effects may reappear. You will be closely monitored, possibly in an intensive care unit, until the effects of flumazenil have completely disappeared.
• If you have received high and/or prolonged (chronic) benzodiazepine treatment at any time within the preceding weeks before flumazenil administration, rapid injection of high doses of flumazenil (greater than 1 mg) should be avoided, as withdrawal symptoms may occur (see section 4. Possible side effects).
• If you have been treated for long periods with high doses of benzodiazepines, the benefits of using Flumazenil Kabi must be weighed against the risk of withdrawal symptoms.
• In children previously sedated with midazolam. These children must be closely monitored in intensive care units for at least 2 hours after administration of Flumazenil Kabi, as repeated sedative effects or respiratory difficulties may occur. For sedation with other benzodiazepines, monitoring should be adjusted according to the expected duration of action.
• If you have epilepsy and have been taking benzodiazepines for a long time, administration of flumazenil is not recommended, as flumazenil may trigger epileptic seizures.
• Seizures or other toxic effects may be more severe in cases of overdose involving multiple drugs (e.g. intoxication with benzodiazepines and cyclic antidepressants).
• If you have severe brain damage (and/or unstable intracranial pressure), you will be carefully monitored, as Flumazenil Kabi may cause an increase in intracranial pressure.
• Flumazenil Kabi is not recommended for the treatment of benzodiazepine dependence or benzodiazepine withdrawal symptoms.
• If you have previously suffered from panic attacks, Flumazenil Kabi may trigger new episodes.
• If you are dependent on alcohol or medications, as the risk of tolerance and dependence on benzodiazepines is higher.
• If your liver does not function properly, elimination of flumazenil may be delayed.

Children

• Children should receive Flumazenil Kabi only after conscious sedation. Available data are insufficient for any other indication. The same applies to children under 1 year of age.

Other medicines and Flumazenil Kabi
Inform your doctor if you are taking or have recently taken any other medicines,
including those obtained without a prescription.
When flumazenil is used in cases of accidental overdose, it should be considered that
toxic effects of other psychotropic medicines (especially tricyclic antidepressants such as
imipramine) taken concomitantly may increase as the benzodiazepine effect wears off.
No interaction has been observed with other central nervous system depressant drugs.

Flumazenil Kabi and alcohol
No interactions between ethanol and flumazenil are known.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Due to insufficient experience with use during pregnancy, Flumazenil Kabi should be used only if the benefits to you outweigh the potential risks to the fetus. Administration of flumazenil during pregnancy is not contraindicated in emergency situations.
It is not known whether flumazenil is excreted in breast milk. Therefore, breastfeeding is recommended to be avoided for 24 hours following administration of flumazenil.

Driving and using machines
After receiving flumazenil to reverse the sedative effects of benzodiazepines, you must not drive vehicles, operate machinery, or perform any other physically or mentally demanding activities for at least 24 hours after sedation, as sedative effects may reappear.

Flumazenil Kabi contains sodium chloride
This medicine contains 3.7 mg of sodium per ml (18.5 mg/vial in the 5 ml vial or 37 mg/vial in the 10 ml vial) of injectable solution. This should be taken into account if you are on a sodium-controlled diet.

3. How to take Flumazenil Kabi

Flumazenil Kabi is administered by intravenous injection (into a vein) or diluted
as an intravenous infusion (over a longer period).
Flumazenil will be administered by an anaesthetist or an experienced doctor. Flumazenil may
be used together with other resuscitation methods.
This medicine is for single use only. Any unused solution must be discarded. The solution should be
visually inspected before use. The solution should only be used if it is clear, colourless, and practically free from particles.
The recommended dose is described as follows:

Patients with renal (kidney) or hepatic (liver) impairment
In patients with impaired hepatic function, elimination of flumazenil may
be delayed and therefore careful dose adjustment is recommended.
Dose adjustments are not required in patients with impaired
renal function.

Use in children

Children over one year of age
Reversal of procedural sedation

Dosage:
The recommended initial dose is 10 micrograms/kg (up to 200 micrograms) administered intravenously over 15 seconds. If, after waiting 45 seconds, the desired level of consciousness has not been achieved, an additional injection of 10 micrograms/kg (up to 200 micrograms) may be given, and if necessary, repeated every 60 seconds (up to a maximum of 4 times) until a maximum dose of 50 micrograms/kg or 1 mg is reached, whichever is lower.

Children under one year of age
There is insufficient data on the use of Flumazenil Kabi in children under one year of age. Therefore, Flumazenil Kabi should be administered to children under one year of age only if the potential benefits outweigh the possible risks.

If you have any doubts about the use of this product, consult your doctor or pharmacist.
For information intended for healthcare professionals, please see the section below.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone 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, does not require treatment), emotional lability, difficulty falling asleep and staying asleep (insomnia), feeling sleepy (somnolence), dizziness, headache, agitation (after rapid injection, does not require treatment), tremors, dry mouth, abnormally rapid and deep breathing (hyperventilation), speech disorders, subjective skin sensations (e.g. cold, heat, tingling, pressure, etc.) in the absence of stimuli (paraesthesia), double vision, strabismus, increased lacrimation, palpitations (after rapid injection, does not require treatment), skin redness (flushing), low blood pressure due to changing from lying to standing position, transient increase in blood pressure (upon waking), vomiting, hiccups, sweating, fatigue, pain at the injection site.

Uncommon (may affect up to 1 in 100 people)
Fear (after rapid injection, does not require treatment), seizures (in patients with epilepsy or severe hepatic insufficiency, especially after long-term treatment with benzodiazepines or overdose of drug mixtures (see section 2. Warnings and precautions), abnormal hearing, rapid or slow heartbeat, premature heartbeat (extrasystoles), breathing difficulties (dyspnoea), cough, nasal congestion, chest pain, chills (after rapid injection, does not require 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, severe allergic reactions (anaphylaxis).

If you have undergone prolonged treatment with benzodiazepines, flumazenil may induce withdrawal symptoms. The symptoms are: tension, agitation, anxiety, emotional lability, confusion, hallucinations, tremors and seizures.

In general, side effects in children do not differ greatly from those in adults. When Flumazenil Kabi is used to wake a child from sedation, abnormal crying, agitation and aggressive reactions have been reported.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Flumazenil Kabi

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 carton. The expiry date refers to the last day of the month.
Do not store above 25°C.
This medicine is for single use only.
Usability after first opening: the medicine must be used immediately.
Stability after dilution: 24 hours.
Chemical and physical stability under usage conditions has been demonstrated for 24 hours at 25°C.
From a microbiological standpoint, the product should be used immediately. If not used immediately, storage times and conditions prior to use are the responsibility of the user and generally should not exceed 24 hours at 2–8°C, unless dilution has been carried out under controlled and validated aseptic conditions.
Do not use this medicine if the solution is not clear and free from particles.
Any unused solution must be disposed of in accordance with local legal requirements.
Do not dispose of medicines via wastewater or household waste.
Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Flumazenil Kabi contains
The active substance is flumazenil.
Each millilitre 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 disodium edetate, glacial acetic acid, sodium chloride, 4% sodium hydroxide solution, water for injections.

Description of the appearance of Flumazenil Kabi and contents of the pack
Flumazenil Kabi is a clear, colourless, concentrated injectable solution in colourless glass vials.
The following packs are available:
Carton pack containing 5 or 10 vials with 5 ml of injectable solution.
Carton pack containing 5 or 10 vials with 10 ml of injectable solution.
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Fresenius Kabi Italia S.r.l.
Via Camagre, 41
37063 Isola della Scala
Verona - Italy

Manufacturers:
Hameln pharmaceuticals GmbH, Langes Feld 13, 31789 Hameln, Germany
Fresenius Kabi Austria GmbH
Hafnerstrasse 36 - 8055 Graz - Austria

This medicinal product is authorised in the European Economic Area Member States under the following names

The following information is intended for healthcare professionals only:

The storage conditions are detailed in section 5. How to store
Flumazenil Kabi.
When Flumazenil Kabi is used for infusion, it must be diluted prior to infusion.
Flumazenil should only be diluted with sodium chloride 9 mg/ml (0.9% w/v) solutions,
glucose 50 mg/ml (5% w/v) solutions, or sodium chloride 4.5 mg/ml (0.45%
w/v) + glucose 25 mg/ml (2.5% w/v) solutions. Compatibility of flumazenil with other injectable
solutions has not been demonstrated.
This medicinal product must not be mixed with other medicinal products except those
mentioned in this section. For further information on dosage instructions, please refer to section 3 of the package leaflet.