Patient leaflet - Byfavo
B. PACKAGE LEAFLET
Package leaflet: Information for the patient
Byfavo 20 mg powder for solution for injection
remimazolam
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▼ This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.
Read all of this leaflet carefully before you are given this medicine because it contains important information for you.
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– Keep this leaflet. You may need to read it again.
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– If you have any further questions, ask your doctor or nurse.
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– If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not
listed in this leaflet. See section 4.
What is in this leaflet
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1. What Byfavo is and what it is used for
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2. What you need to know before you are given Byfavo
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3. How Byfavo is given
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4. Possible side effects
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5. How Byfavo is stored
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6. Contents of the pack and other information
1. What Byfavo is and what it is used for
Byfavo is a medicine that contains the active substance remimazolam.
Remimazolam is one of a group of substances known as benzodiazepines.
Byfavo is a sedative given before a medical test or procedure to make you feel relaxed and sleepy (sedated).
2. What you need to know before you are given Byfavo
You must not be given Byfavo if:
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– you are allergic to remimazolam or other benzodiazepines (such as midazolam) or any of the other ingredients of this medicine (listed in section 6).
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– you have an unstable form of a condition called myasthenia gravis (weakness of muscles) in which your chest muscles that help you breathe get weak
Warnings and precautions
Talk to your doctor or nurse before using Byfavo if you have any severe illness or condition and in particular if:
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– you have very low or very high blood pressure or tend to faint
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– you have heart problems especially a very slow and/or irregular (arrhythmic) heart rate
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– you have any breathing problems including shortness of breath
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– you have severe liver problems.
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– you have a condition called myasthenia gravis in which your muscles are weak
Byfavo can cause temporary loss of memory. Your doctor will assess you before you leave the
hospital or clinic and give you necessary advice.
Children and adolescents
Byfavo should not be given to patients under the age of 18 years because it has not been tested in children and adolescents.
Other medicines and Byfavo
Tell your doctor if you are taking, have recently taken or might take any other medicines, in particular about:
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– opioids (including painkillers such as morphine, fentanyl and codeine or certain cough medicines or medicines for use in drug substitution therapy)
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– antipsychotics (medicines to treat certain psychiatric illnesses)
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– anxiolytics (tranquilizers or medicines that reduce anxiety)
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– medicines that cause sedation (for example temazepam or diazepam)
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– antidepressants (medicines to treat depression)
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– certain antihistamines (medicines to treat allergies)
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– certain antihypertensives (medicines to treat high blood pressure)
It is important to tell your doctor or nurse if you are taking other medicines, as using more than one at the same time can change the effect of the medicines involved.
Byfavo with alcohol
Alcohol can change the effect of Byfavo. Tell your doctor or nurse:
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– how much alcohol you drink regularly or if you have had problems with alcohol use;
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– if you have drunk alcohol in the last 24 hours.
Do not drink alcohol for 24 hours before you are given Byfavo.
Pregnancy and breast-feeding
You should not use Byfavo if you are pregnant or think you may be pregnant. Tell your doctor or nurse if you are pregnant or think you may be pregnant.
If you are a breastfeeding mother, do not breastfeed for 24 hours after you are given this medicine.
Driving and using machines
Byfavo makes you sleepy, forgetful and affects your ability to concentrate. Even though these effects wear off rapidly, you must not drive and operate machinery until these effects are completely gone. Ask your doctor about when you can drive or operate machinery again.
Byfavo contains dextran 40 for injection
This medicine contains 79.13 mg of dextran 40 for injection in each vial. Rarely, dextrans can cause severe allergic reactions. If you have breathing difficulty or swelling or you feel faint, get medical help at once.
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3. How Byfavo is given
Your doctor will decide on the right dose for you.
Your breathing, heart rate and blood pressure will be monitored during the procedure and the doctor will adjust the dose if needed.
A doctor or nurse will give you Byfavo by injection into your vein (blood stream) before and during your medical test or procedure. Byfavo is mixed with sterile saline to make a solution before it is used.
After the procedure
Your doctor or nurse will check on you for a while after sedation to make sure that you feel well and are fit to go home.
If you are given too much Byfavo
If you are given too much Byfavo, you may have the following symptoms:
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– you may feel dizzy
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– you may get confused
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– you may feel sleepy
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– your eyesight may get blurry or you may have involuntary eye movements (dancing eyes)
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– you may get agitated
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– you may feel weak
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– your blood pressure may drop
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– your heartbeat may slow down
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– your breathing may become slow and shallow
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– you may lose consciousness
Your doctor will know how to treat you.
Ask your doctor or nurse if you have any questions 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 users)
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– Low blood pressure
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– Unusually slow or shallow breathing (and low oxygen level in blood)
Common (may affect up to 1 in 10 users)
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– Headache
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– Feeling dizzy
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– Slow heart rate
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– Feeling sick (nausea)
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– Being sick (vomiting)
Uncommon (may affect up to 1 in 100 users)
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– Sleepiness
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– Feeling cold
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– Chills
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– Hiccups
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 By reporting side effects you can help provide more information on the safety of this medicine.
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5. How Byfavo is stored
Professionals in the hospital or clinic are responsible for storing this medicine.
6. Contents of the pack and other information
What Byfavo contains
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– The active substance is remimazolam. Each vial contains remimazolam besylate equivalent to 20 mg of remimazolam. After reconstitution each mL contains 2.5 mg of remimazolam.
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– The other ingredients are:
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– Dextran 40 for injection
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– Lactose monohydrate
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– Hydrochloric acid
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– Sodium hydroxide
See section 2, “Byfavo contains dextran 40 for injection”.
What Byfavo looks like and contents of the pack
Byfavo is a white to off-white powder for solution for injection.
Pack sizes
10 vial pack
Marketing Authorisation Holder
PAION Netherlands B.V.
Vogt 21
6422 RK Heerlen
Netherlands
Manufacturer
PAION Netherlands B.V.
Vogt 21
6422 RK Heerlen
Netherlands
ADOH B.V.
Godfried Bomansstraat 31
6543 JA Nijmegen
Netherlands
This leaflet was last revised in
Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site
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The following information is intended for healthcare professionals only:
Byfavo 20 mg powder for solution for injection
FOR INTRAVENOUS USE ONLY
Must be reconstituted before use with Sodium Chloride 9 mg/mL (0.9%) solution for injection
Read the Summary of Product Characteristics (SmPC) carefully before use.
Remimazolam must only be administered by health care professionals experienced in sedation. The patient should be monitored throughout by a separate healthcare professional, who is not involved in the conduct of the procedure, and whose sole task is to monitor the patient. All personnel must be trained in the detection and management of airway obstruction, hypoventilation and apnoea, including the maintenance of a patent airway, supportive ventilation and cardiovascular resuscitation. The patient's respiratory and cardiac function must be continuously monitored. Resuscitative medicinal products and age- and size-appropriate equipment for restoring airway patency and bag/valve/mask ventilation must be immediately available. A benzodiazepine antagonist (flumazenil, a medicine for counteracting the effects of remimazolam) must be immediately available for use.
Remimazolam dosing should be individually titrated to an effective dose which provides the desired level of sedation and minimises adverse reactions (see Table 1). Additional doses can be administered as needed to induce or maintain the desired level of sedation. At least 2 minutes should elapse prior to administration of any supplemental dose in order to fully assess the sedative effect. Adding or switching to another sedative should be considered if 5 doses of remimazolam within 15 minutes do not result in the desired level of sedation. Remimazolam is associated with fast onset and offset of sedation. In clinical trials, peak sedation occurred 3–3.5 minutes after the initial bolus and patients became fully alert 12–14 minutes from last dose of remimazolam.
Opioid co-administered medicinal products are known to increase the sedative effect of remimazolam and to depress the ventilatory response to carbon dioxide stimulation (see sections 4.4 and 4.5 of the SmPC).
Table 1: Dosing guidelines for adults
| Adults <65 years of age | Elderly >65 years of age and/or with ASA-PS# III-IV and/or body weight <50 kg | |
| Procedural sedation with opioid | Induction Administer opioid Wait 1–2 min Initial dose: Injection: 5 mg (2 mL) over 1 min Wait 2 min Maintenance / titration Injection: 2.5 mg (1 mL) over 15 sec Maximal total dose administrated in the clinical trials was 33 mg. | Induction Administer opioid* Wait 1–2 min Initial dose: Injection: 2.5–5 mg (1–2 mL) over 1 min Wait 2 min Maintenance / titration Injection: 1.25–2.5 mg (0.5–1 mL) over 15 sec Maximal total dose administrated in the clinical trials was 17.5 mg. |
| Procedural sedation without opioid | Induction Injection: 7 mg (2.8 mL) over 1 min Wait 2 min Maintenance / titration Injection: 2.5 mg (1 mL) over 15 sec Maximal total dose administrated in the clinical trials was 33 mg. | Induction Injection: 2.5–5 mg (1–2 mL) over 1 min Wait 2 min Maintenance / titration Injection: 1.25–2.5 mg (0.5–1 mL) over 15 sec Maximal total dose administrated in the clinical trials was 17.5 mg. |
* For administration to patients concomitantly taking opioids, CNS depressants, alcohol or benzodiazepines see section 4.4 of the SmPC.
e.g. 50 micrograms fentanyl or a suitably reduced dose for elderly or debilitated patients. For fentanyl doses administered in clinical trials see section 5.1 of the SmPC.
# American Society of Anesthesiologists Physical Status
Special populations
Elderly, ASA-PS III-IV patients and patients with body weight <50 kg
Elderly patients and patients with ASA-PS III-IV may be more sensitive to the effects of sedatives.
Before administration of remimazolam a careful assessment of the overall condition of patients
>65 years of age and/or with ASA-PS III-IV, especially with low body weight (<50 kg), is therefore of particular relevance when deciding upon individualised dosage adjustments for these patients (see section 4.4 of SmPC).
Renal impairment
No dosage adjustment is required in any grade of renal impairment (including patients with glomerular filtration rate [GFR] <15 mL/min).
Hepatic impairment
The metabolising enzyme (carboxylesterase-1 [CES-1]) for remimazolam is predominantly located in the liver and the clearance of remimazolam is affected by increasing stages of hepatic impairment (see section 5.2 of SmPC). No dose adjustment is recommended for patients with mild (Child-Pugh scores 5 and 6) or moderate (Child-Pugh scores 7 to 9) hepatic impairment. In patients with severe hepatic impairment (Child-Pugh scores 10 to 15; data from only 3 subjects in clinical trials), the clinical effects may be more pronounced and last longer than in healthy subjects. No dose adjustments are required but careful attention should be paid to the timing of titration doses and remimazolam should be carefully titrated to effect in these patients (see section 4.4 of SmPC).
Concomitant use of opioids
Concomitant use of remimazolam and opioids may result in profound sedation, respiratory depression, coma and death. In patients with longer-term opioid use, caution is advised; do not presume these effects will be attenuated. See monitoring section below.
Concomitant use of alcohol / CNS depressants
The concomitant use of remimazolam with alcohol or/and CNS depressants should be avoided.
Alcohol intake should be avoided for 24 hours before remimazolam administration. Such concomitant use has the potential to increase the clinical effects of remimazolam, possibly including severe sedation or clinically relevant respiratory depression. See monitoring section below.
Chronic benzodiazepine use
Patients who receive chronic benzodiazepine therapy (e.g., for insomnia or anxiety disorders) may develop tolerance to the sedative effects of remimazolam. Hence, a larger cumulative dose of remimazolam may be required to achieve the desired level of sedation. It is recommended to follow the titration regimen in section 4.2 of the SmPC and titrate up based on the patient’s sedationresponse, until the desired depth of sedation is achieved. See monitoring section below.
Monitoring
Patients should be monitored closely during and after the procedure for signs and symptoms of respiratory depression and sedation. The physician should also be aware of the typical time taken for patients to recover from the effects of remimazolam and concomitant opioid used in the clinical trials (see section 5.1 of the SmPC), but that this may vary in individual patients. Patients should be closely monitored until they are judged by the healthcare professional to be sufficiently recovered.
Reconstitution instructions
Note: Strict aseptic techniques must be mainted during handling, preparation and use of Byfavo.
To reconstitute, use a sterile needle and a 10 mL sterile syringe, remove the vial cap, puncture the vial stopper at an angle of 90° and add 8.2 mL of sodium chloride 9 mg/mL (0.9%) solution for injection, directing the stream of saline toward the wall of the vial. Gently swirl the vial until the contents are fully dissolved. The reconstituted solution should be clear and colourless to light yellow. The vial delivers a final concentration of 2.5 mg/mL of remimazolam.
The reconstituted solution must be inspected visually for particulate matter and discolouration prior to administration. If particles or discolouration are present then the solution should be discarded.
The reconsituted solution is for single use only, any unused portion must be disposed of in accordance with local requirements.
Incompatibilities
Byfavo is incompatible with Compound Sodium Lactate Solution for infusion.
After reconstitution, this medicinal product must not be mixed with other medicinal products except those mentioned below.
Compatibilities
Reconstituted Byfavo has been shown to be compatible with the following i.v. fluids when administered through the same i.v. line:
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– Glucose (5%) solution for injection
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– Glucose (20%) solution for injection
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– Glucose (5%) – sodium chloride (0.45%) solution for injection
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– Ringers Solution
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– Sodium chloride (0.9%) solution for injection