Flumazenil pharmaselect 0.1 mg/ml

Package leaflet: Information for the user

Flumazenil Pharmaselect, 0.1 mg/ml
Injection solution / concentrate for infusion solution
Flumazenilum
Please read all of this leaflet carefully before use, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor or pharmacist.
• If the patient experiences any adverse reactions, including those not listed in this leaflet, inform your doctor immediately. See section 4.

Table of contents

1. What Flumazenil Pharmaselect 0.1 mg/ml is and what it is used for
2. Important information before use of Flumazenil Pharmaselect 0.1 mg/ml
3. How to use Flumazenil Pharmaselect 0.1 mg/ml
4. Possible side effects
5. How to store Flumazenil Pharmaselect 0.1 mg/ml
6. Contents of the pack and other information

1. What Flumazenil Pharmaselect 0.1 mg/ml is and what it is used for

Flumazenil Pharmaselect 0.1 mg/ml is an antidote used to completely or partially reverse the central sedative effects of benzodiazepines (a class of drugs with calming, sleep-inducing, muscle-relaxing, and anti-anxiety properties).
It is therefore used to awaken patients after certain diagnostic procedures or in intensive care units to reverse sedation in patients who have received sedative medications. Flumazenil Pharmaselect 0.1 mg/ml is also used in the diagnosis and treatment of benzodiazepine poisoning or overdose.

2. Important information before use of Flumazenil Pharmaselect 0.1 mg/ml

When not to use Flumazenil Pharmaselect 0.1 mg/ml

• If the patient has hypersensitivity (allergy) to flumazenil or any of the other ingredients of this medicine listed in section 6.
• If benzodiazepines were administered to treat life-threatening conditions (e.g., to control intracranial pressure or to treat severe epileptic seizures).
• If symptoms of severe poisoning with tricyclic antidepressants are present.
• In cases of mixed poisoning involving benzodiazepines and certain types of antidepressants (so-called tricyclic antidepressants such as imipramine, clomipramine, mirtazapine, and mianserin). The toxic effects of these drugs may be mitigated by the protective action of benzodiazepines. In the presence of significant overdose symptoms of these drugs, Flumazenil Pharmaselect 0.1 mg/ml must not be used to reverse benzodiazepine effects.

Warnings and precautions
Before using Flumazenil Pharmaselect 0.1 mg/ml, discuss with your doctor or nurse.

• If the patient does not wake up after administration of Flumazenil Pharmaselect 0.1 mg/ml, consider other causes of the condition besides benzodiazepine poisoning, as Flumazenil Pharmaselect 0.1 mg/ml specifically reverses the effects of benzodiazepines only.
• If Flumazenil Pharmaselect 0.1 mg/ml is used at the end of surgery to reverse sedation, it should not be administered before the full reversal of neuromuscular blocking agents.
• Since the duration of action of Flumazenil Pharmaselect 0.1 mg/ml is usually shorter than that of benzodiazepines, sedation caused by benzodiazepines may recur. The patient should be closely monitored, preferably in an intensive care unit, until the effect of Flumazenil Pharmaselect 0.1 mg/ml has fully subsided. In patients with concomitant liver dysfunction, the effect may be delayed, and prolonged monitoring may be required.
• In patients previously treated with long-term benzodiazepine therapy, rapid injection of large doses of Flumazenil Pharmaselect 0.1 mg/ml (greater than 1 mg) should be avoided, as this may trigger withdrawal symptoms.
• In patients previously treated with long-term, high-dose benzodiazepines, consider whether the benefits of using Flumazenil Pharmaselect 0.1 mg/ml outweigh the risk of withdrawal symptoms (see section 4: Possible side effects).
• Children previously administered midazolam should be closely monitored in intensive care for at least 2 hours after administration of Flumazenil Pharmaselect 0.1 mg/ml, as sedation and respiratory difficulties may recur. If other benzodiazepines were used for sedation, the duration of monitoring should be adjusted according to the expected duration of action of the respective drug.
• In patients with epilepsy treated long-term with benzodiazepines, Flumazenil Pharmaselect 0.1 mg/ml is not recommended, as it may provoke seizures.
• In cases of severe head or brain injury (and/or unstable intracranial pressure), caution is required, as Flumazenil Pharmaselect 0.1 mg/ml may cause increased intracranial pressure, cerebral perfusion disturbances, or seizures.
• Flumazenil Pharmaselect 0.1 mg/ml is not recommended for the treatment of benzodiazepine dependence or for managing benzodiazepine withdrawal symptoms.
• Flumazenil Pharmaselect 0.1 mg/ml may provoke panic attacks in patients with a history of such episodes.
• In patients experiencing preoperative anxiety or with a history of anxiety disorders.
• In patients with alcohol or drug dependence, there is an increased risk of benzodiazepine dependence or tolerance.
• In patients with heart or liver problems.

Children and adolescents
Children and adolescents previously treated with midazolam should be monitored for at least 2 hours after flumazenil administration due to the potential risk of recurrence of sedation and respiratory disturbances. If other benzodiazepines were used for sedation, monitoring duration should be adjusted to the expected duration of action of the respective drug.
Due to insufficient data, flumazenil should be used with caution in the following cases:

• Reversal of sedation in children under 1 year of age,
• Treatment of overdose in children,
• Neonatal resuscitation,
• Reversal of sedative effects of benzodiazepines used for induction of anesthesia in children.

Until adequate data are available, flumazenil should not be used in children under 1 year of age unless the risk to the patient (especially in cases of accidental overdose) outweighs the potential benefits.
Children and adolescents should receive flumazenil only after intentional sedation.
Flumazenil is not recommended in children and adolescents for indications other than reversal of mild sedation induced by benzodiazepines, due to lack of controlled clinical studies. The same applies to children under 1 year of age.

Flumazenil Pharmaselect 0.1 mg/ml and other medicines
Inform your doctor about all medicines currently or recently taken, including those obtained without a prescription.
When using Flumazenil Pharmaselect 0.1 mg/ml to treat overdose conditions, it should be remembered that the toxic effects of other psychotropic medicinal products (especially tricyclic antidepressants such as imipramine) may be intensified when benzodiazepine effects are blocked. No interactions have been observed with other central nervous system depressants.

Flumazenil Pharmaselect 0.1 mg/ml with food and drink
No interactions with food or drink are known.

Pregnancy, breastfeeding, and fertility
Due to insufficient experience with use during pregnancy, Flumazenil Pharmaselect 0.1 mg/ml should be used only if the expected benefits outweigh the potential risks to the fetus. Use of Flumazenil Pharmaselect 0.1 mg/ml during pregnancy is not contraindicated in critical situations.
It is not known whether Flumazenil Pharmaselect 0.1 mg/ml passes into breast milk. Therefore, breastfeeding should be interrupted for 24 hours after administration of Flumazenil Pharmaselect 0.1 mg/ml.

Before taking any medicine, consult your doctor or pharmacist.

Driving and operating machinery
Patients are advised not to drive, operate machinery, or engage in any other activity requiring mental alertness for at least 24 hours after flumazenil administration, as sedation may recur.

Flumazenil Pharmaselect 0.1 mg/ml contains sodium
Flumazenil Pharmaselect contains approximately 3.6 mg of sodium per ml (18 mg per 5 ml vial or 36 mg per 10 ml vial) of injection solution. This should be taken into account in patients on a controlled sodium diet.

3. How to use Flumazenil Pharmaselect 0.1 mg/ml

Flumazenil Pharmaselect 0.1 mg/ml may be administered only by an anaesthesiologist or a physician experienced in anaesthesia.
The recommended dosing is shown in the table below:

Children and adolescents (from 1 to 17 years of age)
Reversal of sedation while maintaining consciousness
Dosage:
Intravenous injection of 0.01 mg/kg body weight (not exceeding 0.2 mg) administered over 15 seconds. If, after
45 seconds of observation, the desired level of consciousness is not achieved, a further injection may be given
at a dose of 0.01 mg/kg b.w. (not exceeding 0.2 mg), which may be repeated if necessary every 60 seconds (no more than 4 times), without exceeding the maximum total dose of
0.05 mg/kg b.w. or 1 mg, whichever is lower.
Infants under 1 year of age
There is insufficient data on the use of Flumazenil Pharmaselect 0.1 mg/ml in infants under 1 year of age. Therefore, Flumazenil Pharmaselect 0.1 mg/ml may be administered to infants under 1 year of age only when the expected benefits for the patient outweigh the potential risks.
Patients with hepatic or renal impairment
In patients with impaired liver function, elimination of Flumazenil Pharmaselect 0.1 mg/ml may be delayed; therefore, careful dose selection is recommended.
In patients with impaired kidney function, no dosage adjustment is required.
Method of administration
Flumazenil Pharmaselect 0.1 mg/ml is administered either undiluted as an intravenous injection (into a vein) or diluted as an intravenous infusion (prolonged administration).
Flumazenil Pharmaselect 0.1 mg/ml is intended for single use only. Any unused solution should be discarded.
Prior to administration, healthcare personnel must verify that the solution is clear, colourless, and free from particulate matter.
For any further questions regarding the use of this medicinal product, please contact a physician or pharmacist. Information intended exclusively for healthcare professionals is provided in a separate section below.

4. Possible adverse reactions

Like all medicines, Flumazenil Pharmaselect 0.1 mg/ml may cause adverse reactions, although
they do not occur in everyone.

Very common (may occur in more than 1 in 10 people):

• Nausea

Common (may occur in less than 1 in 10 people):

• Hypersensitivity reactions, anaphylaxis.
• Feeling of anxiety (after rapid injection; does not require treatment), difficulty falling asleep and staying asleep (insomnia), feeling of drowsiness (somnolence), emotional lability.
• Headache, dizziness, feeling of agitation, involuntary tremors or shivering, dry mouth, abnormal rapid and deep breathing (hyperventilation), speech disorders, subjective skin sensations (e.g. feeling of cold, heat, tingling, pressure) not caused by external stimuli (paresthesia).
• Double vision, squinting (strabismus), increased lacrimation (production of tears).
• Palpitations (awareness of increased heart rate; after rapid injection; does not require treatment).
• Flushing of the face and neck, drop in blood pressure (especially upon standing), transient increase in blood pressure (upon waking).
• Vomiting, hiccups.
• Excessive sweating.
• Fatigue, pain at the injection site.

Uncommon (may occur in less than 1 in 100 people):

• Anxiety (after rapid injection; does not require treatment).
• Seizures (in patients with epilepsy or severe liver impairment, especially after long-term benzodiazepine treatment or in cases of mixed poisoning).
• Hearing disturbances.
• Heart rate too slow or too fast, premature heartbeats (extrasystoles).
• Breathing difficulties, cough, stuffy nose, chest pain.
• Pallor.
• Chills.

Frequency not known (frequency cannot be estimated from available data):

• Mental changes, euphoria, anxiety, crying spells, aggressive behaviour, panic attacks*.
• Spontaneous movements.
• Increased sensitivity to pain, weight gain, common cold.
• Withdrawal symptoms: feeling of stimulation or anxiety (after rapid injection; does not require treatment), emotional lability, feeling of confusion, sensory disturbances.

In patients who have been using high doses of benzodiazepines and (or) have been taking benzodiazepines
long-term, rapid injection of high doses of flumazenil should be avoided. This may lead to
withdrawal symptoms, such as tension, stimulation, anxiety, emotional lability, confusion, sensory disturbances, hallucinations, involuntary tremors or shivering, and seizures.
Flumazenid should not be administered in high doses too rapidly.
*In patients with a history of anxiety disorders, flumazenil may provoke panic attacks.

Additional adverse reactions in children
Generally, adverse reactions in children do not differ significantly from those observed in adults.
After administration of Flumazenil Pharmaselect 0.1 mg/ml to reverse light sedation in children,
crying spells, agitation, and aggressive behaviour may additionally occur.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed
in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported
directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 2-222 Warsaw
Tel: + 48 22 49 21 301
Fax: + 48 22 49 21 309
e-mail: [email protected] .
Adverse reactions can also be reported to the responsible entity. By reporting
adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Flumazenil Pharmaselect 0.1 mg/ml

Keep out of the sight and reach of children.
Do not use Flumazenil Pharmaselect 0.1 mg/ml after the expiry date stated on the label and carton.
The expiry date refers to the last day of the stated month.
Do not store above 25°C.
Shelf-life after first opening: the medicinal product should be used immediately.
Shelf-life after dilution: 24 hours at a temperature of 2 to 8°C. Intravenous infusion solutions should be discarded after 24 hours.
Do not use this medicine if the solution is not clear and free from particles.
Any unused solution should be disposed of according to local regulations.
Medicines should not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines no longer required.
These measures will help protect the environment.

6. Contents of the package and other information

What Flumazenil Pharmaselect 0.1 mg/ml contains:

• The active substance is flumazenil.

Each millilitre contains 0.1 mg of flumazenil.
Each 5 ml ampoule contains 0.5 mg of flumazenil.
Each 10 ml ampoule contains 1.0 mg of flumazenil.

• Other components are: disodium edetate, acetic acid 1%, sodium chloride, sodium hydroxide solution 1%, water for injections.

What Flumazenil Pharmaselect 0.1 mg/ml looks like and contents of the pack
Flumazenil Pharmaselect 0.1 mg/ml is a clear, colourless concentrate for solution for injection or infusion, supplied in colourless glass ampoules OPC (one point cut) with a blue dot.
The following pack sizes are available:
Cardboard boxes containing 5 or 10 ampoules with 5 ml of solution.
Cardboard boxes containing 5 or 10 ampoules with 10 ml of solution.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Pharmaselect International Beteiligungs GmbH
Ernst-Melchior-Gasse 20, 1020 Vienna, Austria
Phone: +43 1 -786 03 86-0
Fax: +43 1- 786 03 86-20
E-mail: [email protected]

Manufacturer:
Pharmaselect International Beteiligungs GmbH
Ernst-Melchior-Gasse 20, 1020 Vienna, Austria

Information intended exclusively for healthcare professionals:

Prior to administration, Flumazenil Pharmaselect 0.1 mg/ml for infusion must be diluted.
Flumazenil Pharmaselect 0.1 mg/ml may only be diluted with sodium chloride 9 mg/ml (0.9%), glucose 50 mg/ml (5%) solution, or Ringer's solution (8.6 g NaCl, 0.3 g KCl, and 0.33 g CaCl/l).
Compatibility of Flumazenil Pharmaselect 0.1 mg/ml with other infusion solutions has not been established.
This medicinal product must not be mixed with other medicinal products except those mentioned above.
Detailed storage instructions are provided in section 5 How to store Flumazenil Pharmaselect 0.1 mg/ml.
Further information on dosing can be found in section 3 of the patient leaflet.