BYFAVO

Byfavo Generic Name & Formulations

Legal Class

CIV

General Description

Remimazolam 20mg; per vial; lyophilized pwd for IV inj after reconstitution; contains dextran 40; preservative-free.

Pharmacological Class

Benzodiazepine.

How Supplied

Single-patient-use vial (12mL)—10

Manufacturer

Acadia Pharmaceuticals

Generic Availability

Mechanism of Action

Remimazolam 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. Remimazolam, like other benzodiazepines, did not show clear selectivity between subtypes of the GABA_A receptor.

Byfavo Indications

Indications

Induction and maintenance of procedural sedation lasting 30mins or less.

Byfavo Dosage and Administration

Adult

Individualize. Titrate to achieve clinical response. Give by IV inj. Induction: 5mg over 1min; for American Society of Anesthesiologists Physical Status (ASA-PS) III or IV: 2.5–5mg over 1min. Maintenance (as needed): 2.5mg over 15secs; for ASA-PS III or IV: 1.25–2.5mg over 15secs. Must wait ≥2mins prior to administration of any supplemental dose.

Children

<18yrs: not established.

Byfavo Contraindications

Not Applicable

Byfavo Boxed Warnings

Boxed Warning

Personnel and equipment for monitoring and resuscitation. Risks from concomitant use with opioid analgesics and other sedative-hypnotics.

Byfavo Warnings/Precautions

Warnings/Precautions

Should be administered only by trained personnel in procedural sedation, detection/management of airway obstruction, hypoventilation, and apnea. Have resuscitative drugs/equipment, supportive ventilation, reversal agent (eg, flumazenil) readily available. Give supplemental oxygen through the recovery period. Continuously monitor for cardiorespiratory effects (esp. in those with obstructive sleep apnea, elderly, ASA-PS III or IV patients). Severe hepatic impairment. Elderly. Pediatric neurotoxicity. Neonatal sedation and withdrawal syndrome; monitor neonates exposed during pregnancy or labor. Pregnancy (esp. late stage). Nursing mothers: monitor infants; consider interrupting breastfeeding, pumping and discarding breast milk during and for 5hrs after administration.

Byfavo Pharmacokinetics

Absorption

Byfavo overall maximum plasma concentration (C_max) after IV administration of 0.01 to 0.5 mg/kg was 189 to 6,960 ng/mL, and overall area under the concentration versus time curve from time 0 to infinity (AUC_0-∞) was 12.1 to 452 ng∙h/mL; Byfavo cumulative dose versus Byfavo total exposure (AUC_0-∞) suggested a close to dose-proportional relationship. Metabolite C_max was achieved ~20–30 minutes post dose.

Distribution

Byfavo volume of distribution (Vz) was 0.76 to 0.98 L/kg. Plasma protein binding of Byfavo was >91%, primarily to human serum albumin.

Metabolism

The main route of metabolism of Byfavo is via conversion to primary inactive metabolite CNS7054, which is then subject to hydroxylation and glucuronidation. Conversion to CNS7054 is mediated by tissue carboxylesterases (primarily type 1A), with no meaningful contribution by cytochrome P450 enzymes. The half-life of the metabolite was 2.4–3.8 hours.

Elimination

Byfavo has a terminal elimination half-life from plasma of 37–53 minutes and mean distribution half-life (t1/2α) is between 0.5 and 2 minutes. In colonoscopy patients, ~0.003% Byfavo is excreted unchanged in urine, and 50–60% is excreted in urine as the metabolite CNS7054.

Byfavo Interactions

Interactions

Increased risk of profound sedation, respiratory depression, coma, and death with concomitant CNS depressants, including opioid analgesics, other benzodiazepines, propofol; monitor continuously during and through recovery period; titrate Byfavo when concomitant with opioid analgesics and sedative-hypnotics.

Byfavo Adverse Reactions

Adverse Reactions

Hypotension, hypertension, diastolic hyper- or hypotension, systolic hypertension, hypoxia; hypersensitivity reactions.

Byfavo Clinical Trials

See Literature

Byfavo Note