Byfavo Dosing and Administration

Recommended Dosage for Procedural Sedation

The recommended adult dosage of Byfavo and infusion rate by ASA status is shown in the table below. Individualize Byfavo dosing and titrate to desired clinical response.

For Adult Patients
For ASA III-IV Adult Patients
Induction
Administer 5 mg intravenously over a 1-minute time period.
Administer 2.5 mg to 5 mg intravenously over 1 minute based on the general condition of the patient.
Maintenance (as needed) At least 2 minutes must elapse prior to administration of any supplemental dose and assessment of level of sedation
Administer 2.5 mg intravenously over 15 seconds.
Administer 1.25 mg to 2.5 mg intravenously over 15 seconds.

No dosing adjustments are needed for BMI.

Clinical Considerations

  • Half‐life is prolonged with increasing severity of hepatic impairment leading to a need for careful dose titration in patients with severe hepatic impairment
  • Some data suggest a potential of greater sensitivity (a faster onset of loss of consciousness and a longer duration of sedation) of some older individuals; administer supplemental doses of Byfavo slowly to achieve the level of sedation required for the procedure
  • Monitor all patients for cardiorespiratory complications

Preparation of Byfavo

Each single-patient-use, preservative-free vial contains 20 mg Byfavo lyophilized powder for reconstitution, equivalent to 27.2 mg remimazolam besylate. The product must be prepared immediately before use.

  • To reconstitute Byfavo for injection:
    • Add 8.2 mL sterile 0.9% Sodium Chloride Injection, USP, to the vial; direct the stream of solution toward the wall of the vial
    • Gently swirl the vial (do not shake) until the contents are fully dissolved
  • The reconstituted product will deliver a final concentration of 2.5 mg/mL
  • Reconstituted Byfavo can be stored in the vial for up to 8 hours under controlled room temperature at 20°C to 25°C (68°F to 77°F)
  • Once removed from packaging, protect vials from light

Administration With Other Fluids

Byfavo has been shown to be compatible with the following fluids:

  • 0.9% NaCl Injection, USP
  • 5% Dextrose Injection, USP
  • 20% Dextrose Injection, USP
  • 5% Dextrose and 0.45% NaCl Injection, USP
  • Ringer’s Solution

Byfavo is incompatible with:

  • Lactated Ringer’s Solution*
  • Acetated Ringer’s Solution

Byfavo compatibility with other agents has not been adequately evaluated. Do not mix Byfavo with other drugs or fluids prior to administration.

*Lactated Ringer’s Solution is also known as Ringer’s Lactate Solution, Compound Sodium Lactate Solution or Hartmann’s Solution (a solution containing Sodium Chloride, Sodium Lactate, Potassium Chloride, and Calcium Chloride Dihydrate)

Acetated Ringer’s Solution is a solution containing Sodium Chloride, Sodium Acetate, Potassium Chloride, and Calcium Chloride Dihydrate

Indication and Important Safety Information

WARNING: PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION AND RISKS FROM CONCOMITANT USE WITH OPIOID ANALGESICS AND OTHER SEDATIVE-HYPNOTICS

Indication

Byfavo is a benzodiazepine indicated for the induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less.

Important Safety Information

WARNING: PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION AND RISKS FROM CONCOMITANT USE WITH OPIOID ANALGESICS AND OTHER SEDATIVE-HYPNOTICS

Personnel and Equipment for Monitoring and Resuscitation

  • Only personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer Byfavo.
  • Administering personnel must be trained in the detection and management of airway obstruction, hypoventilation, and apnea, including the maintenance of a patent airway, supportive ventilation, and cardiovascular resuscitation.
  • Byfavo has been associated with hypoxia, bradycardia, and hypotension. Continuously monitor vital signs during sedation and during the recovery period.
  • Resuscitative drugs, and age- and size-appropriate equipment for bag-valve-mask–assisted ventilation must be immediately available during administration of Byfavo.

Risks From Concomitant Use With Opioid Analgesics and Other Sedative-Hypnotics

Concomitant use of benzodiazepines, including Byfavo, and opioid analgesics may result in profound sedation, respiratory depression, coma, and death. The sedative effect of intravenous Byfavo can be accentuated by concomitantly administered CNS depressant medications, including other benzodiazepines and propofol. Continuously monitor patients for respiratory depression and depth of sedation.

Contraindication

Byfavo is contraindicated in patients with a history of severe hypersensitivity reaction to dextran 40 or products containing dextran 40.

Personnel and Equipment for Monitoring and Resuscitation

Clinically notable hypoxia, bradycardia, and hypotension were observed in Phase 3 studies of Byfavo. Continuously monitor vital signs during sedation and through the recovery period. Only personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer Byfavo. Administering personnel must be trained in the detection and management of airway obstruction, hypoventilation, and apnea, including the maintenance of a patent airway, supportive ventilation, and cardiovascular resuscitation. Resuscitative drugs, and age- and size-appropriate equipment for bag-valve-mask–assisted ventilation must be immediately available during administration of Byfavo. Consider the potential for worsened cardiorespiratory depression prior to using Byfavo concomitantly with other drugs that have the same potential (eg, opioid analgesics or other sedative-hypnotics). Administer supplemental oxygen to sedated patients through the recovery period. A benzodiazepine reversal agent (flumazenil) should be immediately available during administration of Byfavo.

Risks From Concomitant Use With Opioid Analgesics and Other Sedative-Hypnotics

Concomitant use of Byfavo and opioid analgesics may result in profound sedation, respiratory depression, coma, and death. The sedative effect of IV Byfavo can be accentuated when administered with other CNS depressant medications (eg, other benzodiazepines and propofol). Titrate the dose of Byfavo when administered with opioid analgesics and sedative-hypnotics to the desired clinical response. Continuously monitor sedated patients for hypotension, airway obstruction, hypoventilation, apnea, and oxygen desaturation. These cardiorespiratory effects may be more likely to occur in patients with obstructive sleep apnea, the elderly, and ASA III or IV patients.

Hypersensitivity Reactions

Byfavo contains dextran 40, which can cause hypersensitivity reactions, including rash, urticaria, pruritus, and anaphylaxis. Byfavo is contraindicated in patients with a history of severe hypersensitivity reaction to dextran 40 or products containing dextran 40.

Neonatal Sedation

Use of benzodiazepines during the later stages of pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) in the neonate. Observe newborns for signs of sedation and manage accordingly.

Pediatric Neurotoxicity

Published animal studies demonstrate that anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity increase neuronal apoptosis in the developing brain and result in long-term cognitive deficits when used for longer than 3 hours. The clinical significance of this is not clear. However, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester of gestation through the first several months of life but may extend out to approximately 3 years of age in humans.

Anesthetic and sedation drugs are a necessary part of the care of children needing surgery, other procedures, or tests that cannot be delayed, and no specific medications have been shown to be safer than any other. Decisions regarding the timing of any elective procedures requiring anesthesia should take into consideration the benefits of the procedure weighed against the potential risks.

Adverse Reactions

The most common adverse reactions reported in >10% of patients (N=630) receiving Byfavo 5-30 mg (total dose) and undergoing colonoscopy (two studies) or bronchoscopy (one study) were: hypotension, hypertension, diastolic hypertension, systolic hypertension, hypoxia, and diastolic hypotension.

Use in Specific Populations

Pregnancy
There are no data on the specific effects of Byfavo on pregnancy. Benzodiazepines cross the placenta and may produce respiratory depression and sedation in neonates. Monitor neonates exposed to benzodiazepines during pregnancy and labor for signs of sedation and respiratory depression.

Lactation
Monitor infants exposed to Byfavo through breast milk for sedation, respiratory depression, and feeding problems. A lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk during treatment and for 5 hours after Byfavo administration.

Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Byfavo should not be used in patients less than 18 years of age.

Geriatric Use
No overall differences in safety or effectiveness were observed between these subjects and younger subjects. However, there is a potential for greater sensitivity (eg, faster onset, oversedation, confusion) in some older individuals. Administer supplemental doses of Byfavo slowly to achieve the level of sedation required and monitor all patients closely for cardiorespiratory complications.

Hepatic Impairment

In patients with severe hepatic impairment, the dose of Byfavo should be carefully titrated to effect. Depending on the overall status of the patient, lower frequency of supplemental doses may be needed to achieve the level of sedation required for the procedure. All patients should be monitored for sedation-related cardiorespiratory complications.

Abuse and Dependence

Byfavo is a federally controlled substance (CIV) because it contains remimazolam which has the potential for abuse and physical dependence.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088

Please click to access full Prescribing Information.

BYF HCP ISI 10/2020

Indication and Important Safety Information

WARNING: PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION AND RISKS FROM CONCOMITANT USE WITH OPIOID ANALGESICS AND OTHER SEDATIVE-HYPNOTICS

Indication

Byfavo is a benzodiazepine indicated for the induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less.

Important Safety Information

WARNING: PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION AND RISKS FROM CONCOMITANT USE WITH OPIOID ANALGESICS AND OTHER SEDATIVE-HYPNOTICS

Personnel and Equipment for Monitoring and Resuscitation

  • Only personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer Byfavo.
  • Administering personnel must be trained in the detection and management of airway obstruction, hypoventilation, and apnea, including the maintenance of a patent airway, supportive ventilation, and cardiovascular resuscitation.
  • Byfavo has been associated with hypoxia, bradycardia, and hypotension. Continuously monitor vital signs during sedation and during the recovery period.
  • Resuscitative drugs, and age- and size-appropriate equipment for bag-valve-mask–assisted ventilation must be immediately available during administration of Byfavo.

Risks From Concomitant Use With Opioid Analgesics and Other Sedative-Hypnotics

Concomitant use of benzodiazepines, including Byfavo, and opioid analgesics may result in profound sedation, respiratory depression, coma, and death. The sedative effect of intravenous Byfavo can be accentuated by concomitantly administered CNS depressant medications, including other benzodiazepines and propofol. Continuously monitor patients for respiratory depression and depth of sedation.

Contraindication

Byfavo is contraindicated in patients with a history of severe hypersensitivity reaction to dextran 40 or products containing dextran 40.

Personnel and Equipment for Monitoring and Resuscitation

Clinically notable hypoxia, bradycardia, and hypotension were observed in Phase 3 studies of Byfavo. Continuously monitor vital signs during sedation and through the recovery period. Only personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer Byfavo. Administering personnel must be trained in the detection and management of airway obstruction, hypoventilation, and apnea, including the maintenance of a patent airway, supportive ventilation, and cardiovascular resuscitation. Resuscitative drugs, and age- and size-appropriate equipment for bag-valve-mask–assisted ventilation must be immediately available during administration of Byfavo. Consider the potential for worsened cardiorespiratory depression prior to using Byfavo concomitantly with other drugs that have the same potential (eg, opioid analgesics or other sedative-hypnotics). Administer supplemental oxygen to sedated patients through the recovery period. A benzodiazepine reversal agent (flumazenil) should be immediately available during administration of Byfavo.

Risks From Concomitant Use With Opioid Analgesics and Other Sedative-Hypnotics

Concomitant use of Byfavo and opioid analgesics may result in profound sedation, respiratory depression, coma, and death. The sedative effect of IV Byfavo can be accentuated when administered with other CNS depressant medications (eg, other benzodiazepines and propofol). Titrate the dose of Byfavo when administered with opioid analgesics and sedative-hypnotics to the desired clinical response. Continuously monitor sedated patients for hypotension, airway obstruction, hypoventilation, apnea, and oxygen desaturation. These cardiorespiratory effects may be more likely to occur in patients with obstructive sleep apnea, the elderly, and ASA III or IV patients.

Hypersensitivity Reactions

Byfavo contains dextran 40, which can cause hypersensitivity reactions, including rash, urticaria, pruritus, and anaphylaxis. Byfavo is contraindicated in patients with a history of severe hypersensitivity reaction to dextran 40 or products containing dextran 40.

Neonatal Sedation

Use of benzodiazepines during the later stages of pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) in the neonate. Observe newborns for signs of sedation and manage accordingly.

Pediatric Neurotoxicity

Published animal studies demonstrate that anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity increase neuronal apoptosis in the developing brain and result in long-term cognitive deficits when used for longer than 3 hours. The clinical significance of this is not clear. However, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester of gestation through the first several months of life but may extend out to approximately 3 years of age in humans.

Anesthetic and sedation drugs are a necessary part of the care of children needing surgery, other procedures, or tests that cannot be delayed, and no specific medications have been shown to be safer than any other. Decisions regarding the timing of any elective procedures requiring anesthesia should take into consideration the benefits of the procedure weighed against the potential risks.

Adverse Reactions

The most common adverse reactions reported in >10% of patients (N=630) receiving Byfavo 5-30 mg (total dose) and undergoing colonoscopy (two studies) or bronchoscopy (one study) were: hypotension, hypertension, diastolic hypertension, systolic hypertension, hypoxia, and diastolic hypotension.

Use in Specific Populations

Pregnancy
There are no data on the specific effects of Byfavo on pregnancy. Benzodiazepines cross the placenta and may produce respiratory depression and sedation in neonates. Monitor neonates exposed to benzodiazepines during pregnancy and labor for signs of sedation and respiratory depression.

Lactation
Monitor infants exposed to Byfavo through breast milk for sedation, respiratory depression, and feeding problems. A lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk during treatment and for 5 hours after Byfavo administration.

Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Byfavo should not be used in patients less than 18 years of age.

Geriatric Use
No overall differences in safety or effectiveness were observed between these subjects and younger subjects. However, there is a potential for greater sensitivity (eg, faster onset, oversedation, confusion) in some older individuals. Administer supplemental doses of Byfavo slowly to achieve the level of sedation required and monitor all patients closely for cardiorespiratory complications.

Hepatic Impairment

In patients with severe hepatic impairment, the dose of Byfavo should be carefully titrated to effect. Depending on the overall status of the patient, lower frequency of supplemental doses may be needed to achieve the level of sedation required for the procedure. All patients should be monitored for sedation-related cardiorespiratory complications.

Abuse and Dependence

Byfavo is a federally controlled substance (CIV) because it contains remimazolam which has the potential for abuse and physical dependence.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088

Please click to access full Prescribing Information.

BYF HCP ISI 10/2020

ASA=American Society of Anesthesiologists Physical Status. BMI=body mass index. CI=confidence interval. NaCl=sodium chloride.

Reference: Byfavo [package insert]. Indianapolis, IN: Acacia Pharma Inc.