FLUMAZENIL 0.1 mg/ml Solution

Contents of the leaflet

1. Package Leaflet: Information for the User
2. Flumazenil Pharmaselect, 0.1 mg/ml
3. Solution for Injection / Concentrate for Solution for Infusion
   1. Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.
   2. Table of Contents of the Leaflet
   3. What is Flumazenil Pharmaselect 0.1 mg/ml and what is it used for
   4. Important information before taking Flumazenil Pharmaselect 0.1 mg/ml
   5. When not to use Flumazenil Pharmaselect 0.1 mg/ml
   6. Warnings and precautions
   7. Children and adolescents
   8. Flumazenil Pharmaselect 0.1 mg/ml and other medicines
   9. Flumazenil Pharmaselect 0.1 mg/ml with food and drink
   10. Pregnancy, breastfeeding, and fertility
   11. Driving and using machines
   12. Flumazenil Pharmaselect 0.1 mg/ml contains sodium
   13. Flumazenil Pharmaselect contains approximately 3.6 mg of sodium per ml (18 mg/5 ml vial or 36 mg/10 ml vial)
4. How to take Flumazenil Pharmaselect 0.1 mg/ml
   1. Children and adolescents (from 1 to 17 years of age)
   2. Reversal of sedation with preservation of consciousness
   3. Dosage:
   4. Children under 1 year of age
   5. Patients with liver or kidney disorders
5. Possible side effects
   1. Additional side effects in children
   2. Reporting side effects
6. How to store Flumazenil Pharmaselect 0.1 mg/ml
7. Contents of the pack and other information
   1. What Flumazenil Pharmaselect 0.1 mg/ml contains:
   2. What Flumazenil Pharmaselect 0.1 mg/ml looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. Date of last revision of the leaflet: February 2017
   5. Flumazenil Pharmaselect 0.1 mg/ml.

Package Leaflet: Information for the User

Flumazenil Pharmaselect, 0.1 mg/ml

Solution for Injection / Concentrate for Solution for Infusion

Flumazenil

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

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

Table of Contents of the Leaflet

• 1. What is Flumazenil Pharmaselect 0.1 mg/ml and what is it used for
• 2. Important information before taking Flumazenil Pharmaselect 0.1 mg/ml
• 3. How to take 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 is Flumazenil Pharmaselect 0.1 mg/ml and what is it used for

Flumazenil Pharmaselect 0.1 mg/ml is an antidote used to completely or partially reverse the central sedative effects of benzodiazepines (a group of medicines with sedative, hypnotic, muscle relaxant, and anxiolytic properties). It is used to wake up patients after certain diagnostic tests or in intensive care units to wean patients off sedatives. Flumazenil Pharmaselect 0.1 mg/ml is also used in the diagnosis and treatment of benzodiazepine overdose or poisoning.

• 2.

Important information before taking Flumazenil Pharmaselect 0.1 mg/ml

When not to use Flumazenil Pharmaselect 0.1 mg/ml

• If the patient is allergic(hypersensitive) to flumazenil or any of the other ingredients of this medicine listed in section 6.
• If benzodiazepines were given to treat life-threatening conditions(e.g., to control intracranial pressure or to treat severe seizures).
• If the patient has experienced symptoms of severe poisoning with antidepressant medicines (called tricyclic antidepressants)
• In mixed poisoningwith benzodiazepines and certain types of antidepressants (so-called tricyclic antidepressants, such as imipramine, clomipramine, mirtazapine, and mianserin). The toxic effect of these medicines may be alleviated by the protective effect of benzodiazepines. If symptoms of significant overdose of these medicines occur, Flumazenil Pharmaselect 0.1 mg/ml should not be used to reverse the effects of benzodiazepines.

Warnings and precautions

Before starting treatment with Flumazenil, discuss it with your doctor or nurse.

• If the patient does not wake upafter administration of Flumazenil Pharmaselect 0.1 mg/ml, consider another cause of their condition other than benzodiazepine poisoning, as Flumazenil Pharmaselect 0.1 mg/ml specifically reverses the effects of benzodiazepines.
• If Flumazenil Pharmaselect 0.1 mg/ml is used at the end of surgery to wake up the patient, it should not be administered before the complete reversal of the effects of muscle relaxants.
• Since the duration of action of Flumazenil Pharmaselect 0.1 mg/ml is usually shorter than that of benzodiazepines, sedation caused by benzodiazepines may return. The patient should be closely monitored, preferably in an intensive care unit, until the effects of Flumazenil Pharmaselect 0.1 mg/ml have worn off. Due to the fact that in patients with concomitant liver function disorders, the effect of the medicine may be delayed, as described above, a longer observation time may be required.
• In case of previous long-term benzodiazepine therapy, it is recommended to avoid rapid injectionof large doses of Flumazenil Pharmaselect 0.1 mg/ml (more than 1 mg), as they may cause withdrawal symptoms.
• In case of previous long-term therapy with high dosesof benzodiazepines, it should be considered whether the benefits of using Flumazenil Pharmaselect 0.1 mg/ml outweigh the risk of withdrawal symptoms(see section 4).
• Children who have previously been treated with midazolamshould be closely monitored in an intensive care unit for at least 2 hours after administration of Flumazenil Pharmaselect 0.1 mg/ml, as sedation and respiratory difficulties may return. If other benzodiazepines were used for sedation, the duration of monitoring should be adjusted according to the expected duration of their action.
• In patients with epilepsywho have been treated with benzodiazepines for a long time, Flumazenil Pharmaselect 0.1 mg/ml is not recommended, as it may cause seizures.
• In severe head injuries(and/or unstable intracranial pressure), caution is advised, as Flumazenil Pharmaselect 0.1 mg/ml may cause increased intracranial pressure, cerebral perfusion disorders, or seizures.
• Flumazenil Pharmaselect 0.1 mg/ml is not recommended for the treatment of benzodiazepine dependenceor to combat benzodiazepine withdrawal symptoms.
• Flumazenil Pharmaselect 0.1 mg/ml may cause panic attacksif the patient has a history of panic attacks.
• If the patient experiences anxiety during the preoperative period or has a history of anxiety disorders.
• If the patient has a history of alcohol or drug dependence, there is an increased risk of benzodiazepine dependence or tolerance.
• If the patient has heart or liver problems.

Children and adolescents

Children and adolescents who have been previously treated with midazolamshould be monitored for at least 2 hours after administration of flumazenil, due to the potential risk of return of sedationand respiratory difficulties. If other benzodiazepines were used for sedation, the duration of monitoring should be adjusted according to the expected duration of their action. 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,
• resuscitation of newborns,
• reversal of sedative effects of benzodiazepines used for induction of anesthesia in children.

Until sufficient data are available, flumazenil should not be used in children under 1 year of age, unless the expected benefits to the patient outweigh the potential risks. Children and adolescents should only receive flumazenil after intentionally induced sedation. In children and adolescents, it is not recommended to use flumazenil for other indications than reversal of shallow sedation caused by benzodiazepines, as there are no controlled clinical trials. The same applies to children under 1 year of age.

Flumazenil Pharmaselect 0.1 mg/ml and other medicines

Tell your doctor about all medicines you are taking or have recently taken, including those obtained without a prescription. When using Flumazenil Pharmaselect 0.1 mg/ml to treat overdose, remember that the toxic effects of other psychotropic medicines (especially tricyclic antidepressants, such as imipramine) may be exacerbated by the blockade of benzodiazepine effects. 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 and drink are known.

Pregnancy, breastfeeding, and fertility

Due to insufficient experience with the use of the medicine during pregnancy, Flumazenil Pharmaselect 0.1 mg/ml can only be used when the expected benefits outweigh the potential risks to the fetus. The 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 hoursafter administration of Flumazenil Pharmaselect 0.1 mg/ml. Before taking any medicine, consult your doctor or pharmacist.

Driving and using machines

It is recommended that the patient does not drive a car, does not operate machines, and does not engage in any other activitythat requires mental effort for at least 24 hours after administration of flumazenil, as sedation may return.

Flumazenil Pharmaselect 0.1 mg/ml contains sodium

Flumazenil Pharmaselect contains approximately 3.6 mg of sodium per ml (18 mg/5 ml vial or 36 mg/10 ml vial)

of solution for injection. This should be taken into account in patients controlling their sodium intake.

3. How to take Flumazenil Pharmaselect 0.1 mg/ml

Flumazenil Pharmaselect 0.1 mg/ml may be administered by an anesthesiologist or a doctor experienced in anesthesiology. The recommended dosage is presented in the table below:

Children and adolescents (from 1 to 17 years of age)

Reversal of sedation with preservation of consciousness

Dosage:

Intravenous injection of 0.01 mg/kg body weight (not exceeding 0.2 mg) over 15 seconds. If the desired level of consciousness is not achieved after a 45-second observation period, a subsequent injection of 0.01 mg/kg body weight (not exceeding 0.2 mg) can be administered, which can be repeated every 60 seconds (no more than 4 times), not exceeding the maximum dose of 0.05 mg/kg body weight or 1 mg, whichever is lower.

Children under 1 year of age

There is insufficient data on the use of Flumazenil Pharmaselect 0.1 mg/ml in children under 1 year of age. Therefore, Flumazenil Pharmaselect 0.1 mg/ml can only be administered to children under 1 year of age when the expected benefits to the patient outweigh the potential risks.

Patients with liver or kidney disorders

In patients with impaired liver function, the elimination of Flumazenil Pharmaselect 0.1 mg/ml may be delayed, so cautious dosingis recommended. In patients with kidney disorders, no dose adjustment is required. Administration method Flumazenil Pharmaselect 0.1 mg/ml is administered as an undiluted solution by intravenous injection (into a vein) or as a diluted solution by intravenous infusion (prolonged administration). Flumazenil Pharmaselect 0.1 mg/ml is intended for single use. Unused solution should be discarded. Before administration, medical personnel should check if the solution is clear, colorless, and free of impurities. If you have any further questions about the use of this medicine, ask your doctor or pharmacist. Information intended only for healthcare professionals is included below.

4. Possible side effects

Like all medicines, Flumazenil Pharmaselect 0.1 mg/ml 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, anaphylaxis.
• Feeling of anxiety (after rapid injection; does not require treatment), sleep disorders and insomnia, feeling of drowsiness (drowsiness), emotional instability.
• Headaches, dizziness, feeling of agitation, involuntary tremors or shivers, 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, strabismus, increased tear production.
• Palpitations (awareness of accelerated heart action; after rapid injection; does not require treatment).
• Flushing of the skin of the face and neck, decrease in blood pressure (especially when standing up), transient increase in blood pressure (when waking up).
• Vomiting, hiccups.
• Excessive sweating.
• Fatigue, pain at the injection site.

Uncommon (may affect up to 1 in 100 people):

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

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

• Changes in mental state, euphoria, anxiety, crying spells, aggressive behavior, 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 instability, feeling of confusion, sensory disturbances.

In patients who have taken large doses of benzodiazepines and/or have taken benzodiazepines for a long time, it is recommended to avoid rapid injection of large doses of flumazenil. This may cause withdrawal symptoms, such as tension, stimulation, anxiety, emotional instability, confusion, sensory disturbances, hallucinations, involuntary tremors or shivers, and seizures. Flumazenil should not be administered in large doses too quickly. *In patients with a history of anxiety disorders, flumazenil may cause panic attacks.

Additional side effects in children

Generally, side effects in childrendo not differ significantly from those observed in adults. After administration of Flumazenil Pharmaselect 0.1 mg/ml to reverse shallow sedation in children, additional side effects may include crying spells, stimulation, and aggressive behavior.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products 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]. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

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 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. Solutions for intravenous infusion should be discarded after 24 hours. Do not use this medicine if you notice that the solution is not clear and free of impurities. Unused solution should be disposed of in accordance with local regulations. Medicines should not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Flumazenil Pharmaselect 0.1 mg/ml contains:

• The active substanceis flumazenil.

Each milliliter 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.

• The other ingredientsare: 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 and colorless concentrate for solution for injection or infusion in colorless glass ampoules OPC (one point cut), with a blue dot. The following pack sizes are available: Cardboard boxes with 5 or 10 ampoules containing 5 ml of solution. Cardboard boxes with 5 or 10 ampoules containing 10 ml of solution. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization 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

Date of last revision of the leaflet: February 2017

--------------------------------------------------------------------------------------------------------------- Information intended only for healthcare professionals: Before using Flumazenil Pharmaselect 0.1 mg/ml in infusion, it must be diluted beforehand. Flumazenil Pharmaselect 0.1 mg/ml can only be diluted with sodium chloride 9 mg/ml (0.9%) solution, glucose 50 mg/ml (5%) solution, and Ringer's solution (8.6 g NaCl, 0.3 g KCl, and 0.33 g CaCl/l). The compatibility of Flumazenil Pharmaselect 0.1 mg/ml with other infusion solutions has not been tested. This medicinal product should not be mixed with other medicinal products except those mentioned above. Detailed instructions for storage are included in section 5 How to store Flumazenil Pharmaselect 0.1 mg/ml. More information on dosing can be found in section 3 of the patient leaflet.

Flumazenil Pharmaselect 0.1 mg/ml.