Overview
11 DESCRIPTION Each glass, single-patient-use, sterile vial of BYFAVO (remimazolam) for injection contains 20 mg remimazolam, equivalent to 27.2 mg remimazolam besylate. Remimazolam is a benzodiazepine. Its chemical description is 4H-imidazol[1,2-a][1,4]benzodiazepine-4-propionic acid, 8-bromo-1-methyl-6-(2-pyridinyl)-(4S)-, methyl ester, benzenesulfonate (1:1).
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action BYFAVO is a benzodiazepine. BYFAVO binds to brain benzodiazepine sites (gamma amino butyric acid type A [GABA A ] receptors), while its carboxylic acid metabolite (CNS7054) has a 300 times lower affinity for the receptor. BYFAVO, like other benzodiazepines, did not show clear selectivity between subtypes of the GABA A receptor. 12.2 Pharmacodynamics Dose finding studies determined the IV dosing recommendation of the initial 5 mg bolus, followed by 2.5 mg top-up doses. Median time to peak sedation, defined as the lowest Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score after the initial dose, in the Phase 3 trials was 3 to 3.
Indications
- 1 INDICATIONS AND USAGE BYFAVO ® is indicated for the induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less. BYFAVO (remimazolam) for injection is a benzodiazepine indicated for the induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less. ( 1 )
Common Doses
- 5 mg
- 2.5 mg
- 1.25 mg
- 75 mcg
Dosage
2 DOSAGE AND ADMINISTRATION Individualize and titrate BYFAVO dosing to desired clinical effect. ( 2.2 ) Adult Patients : Administer an initial dose intravenously as a 5 mg push injection over a 1-minute time period. ( 2.2 ) If necessary, administer supplemental doses of 2.5 mg intravenously over a 15-second time period. At least 2 minutes must elapse prior to the administration of any supplemental dose. ( 2.2 ) ASA III-IV Patients (at the discretion of the physician) : Based on the general condition of the patient, administer 2.5 mg to 5 mg over 1-minute time period. ( 2.
Black Box Warning
WARNING: PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION AND RISKS FROM CONCOMITANT USE WITH OPIOID ANALGESICS WARNING: PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION, AND RISKS FROM CONCOMITANT USE WITH OPIOID ANALGESICS AND OTHER SEDATIVE-HYPNOTICS See full prescribing information for complete boxed warning Only personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer BYFAVO. ( 2.1 , 5.
Contraindications
- 4 CONTRAINDICATIONS BYFAVO is contraindicated in patients with a history of severe hypersensitivity reaction to dextran 40 or products containing dextran 40 [see Warnings and Precautions (5.3) ]. Hypersensitivity to dextran 40. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections: Neonatal Sedation and Withdrawal Syndrome [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1) ] The most common adverse reactions (>10%) in patients receiving BYFAVO for procedural sedation are hypotension, hypertension, diastolic hypertension, systolic hypertension, hypoxia, and diastolic hypotension. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Acacia Pharma at 1-877-357-9237 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.
Interactions
- 7 DRUG INTERACTIONS 7.1 Opioid Analgesics and Other Sedative-Hypnotics The sedative effect of intravenous BYFAVO can be accentuated by concomitantly administered CNS depressant medications, including opioid analgesics, other benzodiazepines, and propofol. Continuously monitor vital signs during sedation and through the recovery period. Titrate the dose of BYFAVO when administered with opioid analgesics and sedative-hypnotics to the desired clinical response [see Warnings and Precautions (5.2) ].