Byfavo

Patient Information Leaflet

Byfavo 20 mg powder for concentrate for solution for infusion

remimazolam
Please read this leaflet carefully before you are given 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 or nurse.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor or nurse. See section 4.

Contents of this leaflet

1. What Byfavo is and what it is used for
2. What you need to know before you are given Byfavo
3. How Byfavo is administered
4. Possible side effects
5. How to store Byfavo
6. Contents of the pack and other information

1. What Byfavo is and what it is used for
Byfavo is a medicine containing the active substance remimazolam.
Remimazolam belongs to a group of medicines called benzodiazepines.
Byfavo is a sedative given before a medical examination or procedure to induce relaxation and drowsiness.

2. What you should know before you are given Byfavo

Do not receive Byfavo if:

• you are allergic to remimazolam or to other benzodiazepines (such as midazolam) or to any of the other ingredients of this medicine (listed in section 6);
• you have an unstable form of myasthenia gravis (muscle weakness), in which the chest muscles that help you breathe become weakened.

Warnings and precautions
Talk to your doctor or nurse before receiving Byfavo if you have a disease or severe condition, especially if:

• you have very low or very high blood pressure or tend to faint;
• you have heart problems, particularly a very slow and/or irregular heartbeat (arrhythmia);
• you have breathing problems including shortness of breath;
• you have severe liver problems;
• you suffer from myasthenia gravis, a condition characterized by muscle weakness;
• you regularly use recreational drugs or have had problems with drug use in the past.

Byfavo may cause temporary memory loss. Your doctor will assess your condition before allowing you to leave the hospital or clinic and will provide you with the necessary advice.
Children and adolescents
Byfavo must not be administered to patients under 18 years of age, as it has not been studied in children and adolescents.
Other medicines and Byfavo
Inform your doctor if you are taking, have recently taken, or might take any other medicines, especially:

• opioids (including painkillers such as morphine, fentanyl and codeine or certain cough medicines or medicines used in drug substitution therapy),
• antipsychotics (medicines used to treat certain psychiatric disorders),
• anxiolytics (tranquilizers or medicines that reduce anxiety),
• medicines that cause sedation (such as temazepam or diazepam),
• antidepressants (medicines used to treat depression),
• certain antihistamines (medicines used to treat allergies),
• certain antihypertensives (medicines used to treat high blood pressure).

It is important to inform your doctor or nurse if you are taking other medicines, as concomitant use of multiple medicines may alter the effects of the medicines involved.
Byfavo and alcohol
Alcohol may alter the effect of Byfavo. Inform your doctor or nurse:

• about the amount of alcohol you regularly consume or if you have had problems with alcohol consumption.

Do not drink alcohol within 24 hours before administration of Byfavo.
Pregnancy and breastfeeding
Do not use Byfavo if you are pregnant or suspect you may be pregnant. Inform your doctor or nurse if you are pregnant or suspect you may be pregnant.
If you are breastfeeding, do not breastfeed for 24 hours after administration of this medicine.
Driving and using machines
Byfavo causes drowsiness, memory loss, and affects your ability to concentrate. Although these effects disappear rapidly, you must not drive or operate machinery until these effects have completely disappeared. Ask your doctor when you can drive or use machines again.
Byfavo contains dextran 40 for injection
This medicine contains 79.13 mg of dextran 40 for injection in each vial.
Dextrans rarely may cause severe allergic reactions. If you experience difficulty breathing, swelling, or feel faint, consult your doctor immediately.

3. How Byfavo is administered

Your doctor will prescribe the correct dose for you.
During the procedure, your breathing, heart rate, and blood pressure will be monitored and, if necessary, your doctor will adjust the dose.
A doctor or nurse will administer Byfavo to you as an intravenous injection (into the bloodstream) before and during the medical examination or procedure. Before use, Byfavo is mixed with a sterile saline solution to prepare an infusion solution.

After the procedure
After sedation, the doctor or nurse will monitor you for some time to ensure that you feel well and are able to go home safely.

If you have been given too much Byfavo
If you have been given an overdose of Byfavo, you may experience the following symptoms:

• you may feel dizzy
• you may feel confused
• you may feel sleepy
• your vision may become blurred or you may have involuntary eye movements (dancing eyes)
• you may feel agitated
• you may feel weak
• your blood pressure may drop
• your heartbeat may slow down
• your breathing may become slow and weak
• you may lose consciousness

Your doctor knows how to treat you.
Speak to your doctor or nurse if you have any doubts about the use of this medicine.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

• Low blood pressure
• Unusually slow or weak breathing (and low blood oxygen levels)

Common (may affect up to 1 in 10 people)

• Headache
• Dizziness
• Slow heart rate
• Feeling unwell (nausea)
• Malaise (vomiting)

Uncommon (may affect up to 1 in 100 people)

• Drowsiness
• Feeling cold
• Chills
• Hiccups

Not known (frequency cannot be estimated from the available data)

• Sudden severe allergic reaction

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly through the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Byfavo

Healthcare operators in hospitals or clinics are responsible for the storage of this
medicinal product.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial. The expiry date refers to the last day of that month.
Chemical and physical stability has been demonstrated for 24 hours at 20-25°C.
From a microbiological standpoint, unless the method of opening/reconstitution/dilution excludes the risk of microbial contamination, the product should be used immediately. Otherwise, the duration and conditions of storage during use are the responsibility of the user (see section 6.3 of the SmPC).
Do not use this medicine if you notice visible particles or discoloration.

6. Pack contents and other information

What Byfavo contains

• The active substance is remimazolam. Each vial contains remimazolam besilate equivalent to 20 mg of remimazolam. After reconstitution, each mL contains 2.5 mg of remimazolam.
• The other components are:
• dextran 40 for injectable preparations
• lactose monohydrate
• hydrochloric acid
• sodium hydroxide See section 2, “Byfavo contains dextran 40 for injectable preparations”.

Description of the appearance of Byfavo and pack contents
Byfavo is a white to off-white powder for injectable solution.
Number of dosage units
Pack of 10 vials
Marketing Authorisation Holder
PAION Pharma GmbH
Heussstraße 25
52078 Aachen
Germany
Manufacturer
PAION Deutschland GmbH
Heussstraße 25
52078 Aachen
Germany
PAION Pharma GmbH
Heussstraße 25
52078 Aachen
Germany
For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu .

The following information is intended exclusively for healthcare professionals:
Byfavo 20 mg powder for injectable solution
FOR INTRAVENOUS USE ONLY
Must be reconstituted prior to use with sodium chloride 9 mg/mL (0.9 %) injectable solution
Read the product characteristics summary (SmPC) carefully before use.
Remimazolam must be administered only by healthcare professionals experienced in sedation procedures. Throughout the duration of treatment, the patient must be monitored by another healthcare professional who is not involved in performing the procedure and whose sole responsibility is patient monitoring. This personnel must be trained in the detection and management of airway obstruction, hypoventilation, and apnea, as well as in maintaining airway patency, providing assisted ventilation, and performing cardiovascular resuscitation. The patient's cardiac and respiratory function must be continuously monitored. Resuscitation medications, age-appropriate and properly sized equipment for restoring airway patency, and a self-inflating bag for ventilation must be immediately available. A benzodiazepine antagonist (flumazenil) must also be readily available.

Instructions for reconstitution
NB: Strict aseptic techniques must be used during handling, preparation, and administration of Byfavo.
For reconstitution, use a sterile needle and a 10 mL sterile syringe. Remove the closure cap from the vial, pierce the vial stopper at a 90° angle, and add 8.2 mL of sodium chloride 9 mg/mL (0.9 %) injectable solution, directing the saline flow towards the vial wall. Gently swirl the vial until the contents are completely dissolved. The reconstituted solution should be clear, colourless to pale yellow. The vial provides a final concentration of 2.5 mg/mL of remimazolam.
The reconstituted solution should be inspected visually before administration to ensure absence of particulate matter and discoloration. If particles or discoloration are present, the solution must be discarded.
The reconstituted solution is for single use only; any unused portion must be disposed of in accordance with local regulations.

Incompatibilities
Byfavo is incompatible with Ringer's lactate solution (also known as compound sodium lactate solution or Hartmann's solution), Ringer's acetate solution, and Ringer's sodium bicarbonate infusion solution.
After reconstitution, this medicinal product must not be mixed with other medicinal products except those mentioned below.

Compatibility
Reconstituted Byfavo has been shown to be compatible with the following intravenous fluids when administered through the same intravenous line:

• Glucose (5 %) injectable solution
• Glucose (20 %) injectable solution
• Glucose (5 %) – sodium chloride (0.45 %) injectable solution
• Ringer's solution
• Sodium chloride (0.9 %) injectable solution

Compatibility with other intravenous fluids has not been evaluated.

Shelf life
Chemical and physical in-use stability has been demonstrated for 24 hours between 20 °C and 25 °C.
From a microbiological standpoint, unless the method of opening/reconstitution/dilution excludes the risk of microbial contamination, the product should be used immediately. Otherwise, the times and conditions of storage during use are the responsibility of the user.

Special precautions for storage
Keep vials in the outer cardboard box to protect the medicinal product from light.

Patient information leaflet

Byfavo 50 mg powder for concentrate for solution for injection/infusion

remimazolam
Please read this leaflet carefully before this medicine is administered to you 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 or nurse.
• If you get any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

1. What Byfavo is and what it is used for
2. What you need to know before you are given Byfavo
3. How Byfavo is administered
4. Possible side effects
5. How to store Byfavo
6. Contents of the pack and other information

1. What Byfavo is and what it is used for
Byfavo is a medicine containing the active substance remimazolam. It belongs to a group of medicines known as benzodiazepines. Byfavo is administered to induce loss of consciousness (to fall asleep) before a surgical procedure.

2. What you need to know before you are given Byfavo

Do not be given Byfavo if:

• you are allergic to remimazolam or to other benzodiazepines (such as midazolam) or to any of the other ingredients of this medicine (listed in section 6);
• you have an unstable form of myasthenia gravis (muscle weakness), in which the chest muscles that help you breathe become weakened.

Warnings and precautions
Talk to your doctor or nurse before receiving Byfavo if you have any illness or severe condition, especially if:

• you have very low or very high blood pressure or tend to faint;
• you have heart problems, particularly a very slow and/or irregular heartbeat (arrhythmia);
• you have breathing problems including shortness of breath;
• you have severe liver problems;
• you have myasthenia gravis, a condition characterized by muscle weakness;
• you regularly use recreational drugs or have had problems with drug use in the past.

Byfavo may cause temporary memory loss. Your doctor will assess your condition before allowing you to leave the hospital or clinic and will provide you with necessary advice.
Some patients undergoing surgical procedures may experience sudden mental confusion (delirium) after the procedure. This is more common in patients undergoing major surgery, who are older, have memory problems, are exposed to deep anaesthesia/sedation and/or for a prolonged period, or have infections. Patients with delirium may have difficulty following a conversation, may be more confused at certain times than others, become agitated and restless, or become drowsy and very sluggish, and may have disturbing dreams or hear noises or voices that are not real.
Your doctor will assess your condition and arrange for the necessary treatment to manage it.
Benzodiazepines sometimes cause effects opposite to the expected effect of the medicine. These may be called "paradoxical" effects. They include, for example, aggressive behaviour, agitation, anxiety.
They are more common in elderly people when they receive high doses of the medicine or when the medicine is administered rapidly.

Children and adolescents
Byfavo must not be given to patients under 18 years of age because it has not been studied in children and adolescents.

Other medicines and Byfavo
Tell your doctor if you are taking, have recently taken, or might take any other medicines, especially:

• opioids (including painkillers such as morphine, fentanyl and codeine or certain cough medicines or medicines used in drug substitution therapy),
• antipsychotics (medicines for the treatment of certain psychiatric disorders),
• anxiolytics (tranquillisers or medicines that reduce anxiety),
• medicines that cause sedation (such as temazepam or diazepam),
• antidepressants (medicines for the treatment of depression),
• certain antihistamines (medicines for the treatment of allergies),
• certain antihypertensives (medicines for the treatment of high blood pressure).

It is important to inform your doctor or nurse if you are taking other medicines, as taking several medicines together may alter the effects of the medicines in question.

Byfavo and alcohol

• Alcohol may alter the effect of Byfavo. Inform your doctor or nurse about the amount of alcohol you regularly consume or if you have had problems with alcohol consumption.

Do not drink alcohol within 24 hours before receiving Byfavo.

Pregnancy and breastfeeding
Do not use Byfavo if you are pregnant or suspect you may be pregnant. Inform your doctor or nurse if you are pregnant or suspect you may be pregnant.
If you are breastfeeding, do not breastfeed for 24 hours after administration of this medicine.

Driving and using machines
Byfavo causes drowsiness, memory loss and affects your ability to concentrate. Even though these effects disappear rapidly, you must not drive or operate machinery until these effects have completely worn off. Ask your doctor when you can drive or operate machinery again.

Byfavo contains dextran 40 for injectable preparations
This medicine contains 198 mg of dextran 40 for injectable preparations in each vial.
Dextrans rarely may cause severe allergic reactions. If you experience difficulty breathing, swelling or feel faint, consult your doctor immediately.

3. How Byfavo is administered

Your doctor will prescribe the correct dose for you.
During the procedure, your breathing, heart rate, and blood pressure will be monitored and, if necessary, your doctor will adjust the dose.
A doctor or nurse will administer Byfavo to you as an intravenous injection (into the bloodstream) before and during surgery. Before use, Byfavo is mixed with a sterile sodium chloride solution to prepare a solution. You may need several medications to keep you asleep, prevent pain, and maintain proper breathing with stable blood pressure. Your doctor will decide which medications you require.
Recovery time after stopping administration is expected to be 12–15 minutes.
If you have been given too much Byfavo
If you have been given an excessive dose of Byfavo, you may experience the following symptoms:

• your blood pressure may drop
• your heartbeat may slow down
• your breathing may become slow and weak

Your doctor will know how to treat you.
Speak to your doctor or nurse if you have any doubts about the use of this medicine.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

• Slow heart rate
• Low blood pressure
• Feeling unwell (nausea)
• Feeling unwell (vomiting)

Common (may affect up to 1 in 10 people)

• Feeling restless
• Headache
• Dizziness
• Unusually slow or weak breathing (and low oxygen levels in the blood)
• Prolonged drowsiness or feeling of unconsciousness after the procedure
• Shivering

Uncommon (may affect up to 1 in 100 people)

• Hiccups
• Abnormal positioning of the tongue in the mouth (higher, towards the palate, and further back in the mouth than normal)
• Feeling cold

Not known (frequency cannot be estimated from the available data)

• Sudden severe allergic reaction

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, tell your doctor or nurse.
You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Byfavo

Healthcare operators in hospitals or clinics are responsible for the storage of this
medicinal product.
Keep this medicine out of the sight and reach of children.
Do not use this medicinal product after the expiry date stated on the carton and vial. The expiry date refers to the last day of that month.
Chemical and physical stability has been demonstrated for 24 hours at 20-25°C.
From a microbiological standpoint, unless the method of opening/reconstitution/dilution excludes the risk of microbial contamination, the product should be used immediately. Otherwise, the duration and conditions of storage during use are the responsibility of the user (see section 6.3 of the SmPC).
Do not use this medicinal product if you notice visible particles or discoloration.

6. Pack contents and other information

What Byfavo contains

• The active substance is remimazolam. Each vial contains remimazolam besylate equivalent to 50 mg of remimazolam. After reconstitution, each mL contains 5 mg of remimazolam, which is further diluted before use. Your doctor will determine the exact dose suitable for you.
• The other components are:
• dextran 40 for injectable preparations
• lactose monohydrate
• hydrochloric acid
• sodium hydroxide

See section 2, “Byfavo contains dextran 40 for injectable preparations”.
Description of the appearance of Byfavo and pack contents
Byfavo is a white/whiteish powder for concentrate for solution for injection/infusion (powder for concentrate).
Number of dosage units
Pack of 10 vials
Marketing Authorization Holder
PAION Pharma GmbH
Heussstraße 25
52078 Aachen
Germany
Manufacturer
PAION Deutschland GmbH
Heussstraße 25
52078 Aachen
Germany
PAION Pharma GmbH
Heussstraße 25
52078 Aachen
Germany
For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu .
<------------------------------------------------------------------------------------------------------------------------>
The following information is intended for healthcare professionals only:
Byfavo 50 mg powder for concentrate for solution for injection/infusion
FOR INTRAVENOUS USE ONLY
Must be reconstituted and further diluted with sodium chloride 9 mg/mL (0.9%) injection solution before use
Read the Summary of Product Characteristics (SmPC) carefully before use.
Remimazolam must be administered exclusively in hospitals or in properly equipped day surgery units by physicians trained in anaesthesia.
Cardiac and respiratory functions must be continuously monitored (e.g., electrocardiogram [ECG], pulse oximetry), and facilities for airway maintenance and artificial ventilation, as well as other resuscitation equipment, must be immediately available at all times.
Instructions for use
General precautions
Each vial is for single use only. Reconstitution and dilution must be performed using aseptic techniques. Once the vial has been opened, the contents must be used immediately (section 6.3 of the SmPC). To avoid consequences, the needle should be inserted at an angle between 45° and 60°, with the bevel of the needle tip facing upwards (i.e., away from the stopper), sometimes referred to as "bevel up". Apply slight pressure and gradually increase the angle as the needle enters the vial. The needle should be at a 90° angle when the bevel passes through the stopper.
Instructions for reconstitution
Byfavo must be reconstituted by adding 10 mL of sodium chloride 9 mg/mL (0.9%) injection solution and gently swirling until the powder is completely dissolved. The reconstituted Byfavo solution will be clear and colourless to pale yellow. If visible particulate matter or discoloration is observed, the solution must be discarded.
Instructions for dilution
For administration, the reconstituted solution must be further diluted. The appropriate volume of the reconstituted remimazolam solution should be withdrawn from one or more vials and added to a syringe or infusion bag containing sodium chloride 9 mg/mL (0.9%) injection solution to achieve a final concentration of 1–2 mg/mL of remimazolam (Table 1).
Table 1. Dilution instructions

Administration with other liquids
Compatibility has been demonstrated for the reconstitution and dilution of Byfavo in sodium chloride (0.9%) as described above with the following:
5% glucose infusion;
20% glucose p/v, solution for infusion;
0.45% sodium chloride p/v and 5% glucose p/v, solution for infusion;
0.9% sodium chloride, infusion for intravenous use;
Ringer's solution (sodium chloride 8.6 g/l, potassium chloride 0.3 g/l, calcium chloride dihydrate 0.33 g/l).

This medicinal product must not be mixed or administered simultaneously in the same infusion line with medicinal products other than the fluids described in this section.

Incompatibilities
Incompatibilities between Byfavo and concomitantly administered solutions may cause precipitation/turbidity, which could lead to occlusion at the vascular access site. Byfavo is incompatible with Ringer's lactate solution (also known as compound sodium lactate solution or Hartmann's solution), Ringer's acetate solution, Ringer's sodium bicarbonate solution for infusion, and other alkaline solutions, because the solubility of the product is low at pH 4 or higher.

This medicinal product must not be mixed or administered simultaneously in the same infusion line with other medicinal products except those mentioned in "Administration with other liquids".

In-use stability after reconstitution
Chemical and physical stability during use has been demonstrated for 24 hours at 20 °C to 25 °C.
From a microbiological standpoint, unless the method of opening/reconstitution/dilution excludes the risk of microbial contamination, the product should be used immediately. Otherwise, the duration and conditions of storage during use are the responsibility of the user.

Special precautions for storage
Keep vials in the outer cardboard box to protect the medicinal product from light.