Procedural sedation, Induction and maintenance

Benzodiazepine
Remimazolam is a benzodiazepine that 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."""

1.Distribution: Vd: 0.76 to 0.98 L/kg.
2.Protein binding: >91%; primarily to albumin.
3.Metabolism: Via conversion to primary inactive metabolite CNS7054 by tissue carboxylesterases (primarily type 1A), which is then subject to hydroxylation and glucuronidation.
4.Half-life elimination: 37 to 53 minutes.
5.Excretion: Urine (0.003% [unchanged]; 50% to 60% [inactive metabolite]).

Severe hypersensitivity reaction to dextran 40 or products containing dextran 40 .

There have been reports of newborns exhibiting sedative symptoms when mothers used benzodiazepines during late pregnancy. Although there are no data on the effects of BYFAVO use in pregnant women, observational studies of other benzodiazepines in pregnant women have not established drug-related risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, a study in pregnant rabbits administered 30 mg intravenously—equivalent to four times the maximum recommended human dose (MRHD)—during organogenesis observed reduced embryonic and fetal body weights, but no evidence of malformations or fetal death. Adequate reproductive and developmental toxicology studies in rodents to fully assess the effects of BYFAVO have not been completed. Published studies in pregnant non-human primates indicate that exposure to anesthetic and sedative drugs that block NMDA receptors and/or enhance GABA activity for more than 3 hours during peak brain development increases neuronal apoptosis in the offspring’s developing brain. There are no data on drug exposure in non-human primates equivalent to human pregnancy before the third trimester. The estimated background risks of major birth defects and miscarriage in the general population, including the population of pregnant women, are unknown for the specific population using BYFAVO. In the United States general population, the clinically recognized estimated background risk for major birth defects and miscarriage is approximately 2-4% and 15-20%, respectively. Data on BYFAVO use in pregnant women are either unavailable or limited (fewer than 300 pregnancy outcomes). Animal studies have not shown direct or indirect harmful effects related to reproductive toxicity. As a precautionary measure, the use of BYFAVO during pregnancy is best avoided. 【文字內容由仿單翻譯而來】

There are currently no data on remimazolam in human breast milk, its effects on breastfed infants, or on milk production. Remimazolam is present in animal milk. When a drug is found in animal milk, it is likely to be present in human breast milk as well. There have been reports of infants being exposed to benzodiazepines through breastfeeding. Infants exposed to BYFAVO through breastfeeding should be monitored for sedation, respiratory depression, and feeding difficulties. During BYFAVO administration and for 5 hours afterward (approximately 5 elimination half-lives), breastfeeding mothers should consider interrupting breastfeeding, expressing and discarding breast milk to minimize drug exposure to the nursing infant. When weighing the developmental and health benefits of breastfeeding, the mother’s clinical need for BYFAVO and the potential adverse effects from BYFAVO or the underlying maternal condition on the nursing infant should also be considered. It is not yet known whether remimazolam and its major metabolite (CNS7054) are excreted into human milk. Available animal toxicology data indicate that remimazolam and CNS7054 are excreted into milk. Because the risk to newborns/infants cannot be excluded, remimazolam should be avoided in breastfeeding women. If remimazolam use is necessary, it is recommended to discontinue breastfeeding until 24 hours after the last dose. 【文字內容由仿單翻譯而來】

>10%: Cardiovascular: Bradycardia (4% to 11%), decreased diastolic blood pressure (8% to 14%), hypertension (20% to 28%), hypotension (33% to 39%; increased diastolic blood pressure 10% to 25%), systolic hypertension (5% to 22%) Respiratory: Hypoxia (22%), tachypnea (14%) 1% to 10%: Cardiovascular: Tachycardia (8%) Gastrointestinal: Nausea (4%) Nervous system: Headache (3%) Miscellaneous: Fever (4%)

Induction of procedural sedation:
1.Healthy adults: IV: 5 mg over 1 minute.
2.American Society of Anesthesiologists physical status III or IV patients: IV: 2.5 to 5 mg over 1 minute based on general condition of patient.
Maintenance of procedural sedation:
1.Healthy adults: IV: 2.5 mg over 15 seconds as needed; at least 2 minutes must elapse prior to administration of any supplemental dose.
2.American Society of Anesthesiologists physical status III or IV patients: IV: 1.25 to 2.5 mg over 15 seconds as needed; at least 2 minutes must elapse prior to administration of any supplemental dose.

N/A

There are no dosage adjustments provided in the manufacturer’s labeling; however, pharmacokinetics were not altered in patients with mild to severe renal impairment.

1.Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling.
2.Severe impairment: There are no specific dosage adjustments provided in the manufacturer’s labeling; use caution and carefully titrate to effect; lower frequency of supplemental doses may be needed.

a) Store at a controlled room temperature between 20 and 25 degrees C, with excursions permitted between 15 and 30 degrees C. Protect from light once removed from packaging. b) After reconstitution, drug can be stored in the vial for up to 8 hours at a controlled room temperature between 20 and 25 degrees C. Protect from light. After 8 hours, discard unused portion.