Remimazolam Explained

Verifiedfields:changed
Watchedfields:changed
Verifiedrevid:451607085
Width:222
Tradename:Byfavo
Dailymedid:Remimazolam
Routes Of Administration:Intravenous
Atc Prefix:N05
Atc Suffix:CD14
Legal Ca:Schedule IV
Legal De:Anlage III
Legal Uk:PSA
Legal Us:Schedule IV
Legal Eu:Rx-only
Legal Eu Comment:[1] [2]
Elimination Half-Life:45 - 70 minutes
Index2 Label:as salt
Cas Number:308242-62-8
Pubchem:9867812
Drugbank:DB12404
Chemspiderid:8043503
Unii:7V4A8U16MB
Kegg:D11788
Kegg2:D10194
Chembl:4297526
Synonyms:CNS-7056[3]
Iupac Name:methyl 3-[(4''S'')-8-bromo-1-methyl-6-(pyridin-2-yl)-4''H''-imidazo[1,2-''a''][1,4]benzodiazepin-4-yl]propanoate
C:21
H:19
Br:1
N:4
O:2
Smiles:COC(=O)CC[C@@H]1N=C(c2ccccn2)c2cc(Br)ccc2-n2c(C)cnc21
Stdinchi:1S/C21H19BrN4O2/c1-13-12-24-21-17(7-9-19(27)28-2)25-20(16-5-3-4-10-23-16)15-11-14(22)6-8-18(15)26(13)21/h3-6,8,10-12,17H,7,9H2,1-2H3/t17-/m0/s1
Stdinchikey:CYHWMBVXXDIZNZ-KRWDZBQOSA-N

Remimazolam, sold under the brand name Byfavo, is a medication for the induction and maintenance of procedural sedation in adults for invasive diagnostic or surgical procedures lasting 30 minutes or less.[4] [5] [6] It is a benzodiazepine drug, developed by PAION AG in collaboration with several regional licensees as an alternative to the short-acting imidazobenzodiazepine midazolam, for use in the induction of anesthesia and conscious sedation for minor invasive procedures. Remimazolam was found to have both a more rapid onset and a shorter duration than midazolam, and human clinical trials showed a faster recovery time and predictable, consistent pharmacokinetics, suggesting some advantages over existing drugs for these applications.[7] [8]

The most common side effects for procedural sedation include low blood pressure, high blood pressure, diastolic hypertension, systolic hypertension, low blood oxygen level, and diastolic hypotension.

Remimazolam was approved for medical use in the United States in July 2020, and in the European Union in March 2021.

Medical uses

Remimazolam is indicated for the induction and maintenance of procedural sedation in adults (lasting 30 minutes or less in the USA).[9]

History

Remimazolam was approved for medical use in the United States in July 2020.

The U.S. Food and Drug Administration (FDA) approved remimazolam based on evidence from three clinical trials (Trial 1/NCT02290873, Trial 2/NCT02296892 and Trial 3/NCT02532647) in adults undergoing short procedures. Trials were conducted at 32 sites in the United States.

Trials 1 and 3 were conducted in participants undergoing colonoscopy and Trial 2 was conducted in participants undergoing bronchoscopy procedures.

In the trials, participants were randomly divided in three groups: one group received remimazolam, one group received placebo and one group received midazolam (similar, but approved drug). In the first two groups, neither participants nor investigators knew which medications were given and participants could also receive midazolam as a rescue drug when needed for sedation. In the third group, all participants received midazolam only Additionally, in all three trials participants received a medication for pain control

Trials 1 and 2 compared participants who received remimazolam to participants in the other two groups, measuring the success of sedation with the set of pre-determined criteria. Data from Trial 3 were used primarily to assess the side effects of remimazolam when multiple dosing is used.

Society and culture

Legal status

On 28 January 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Byfavo, intended for procedural sedation. The applicant for this medicinal product is PAION Netherlands B.V.[10] Remimazolam (Byfavo) was approved for medical use in the European Union in March 2021.

Research

Phase I[11] and Ib[12] dose-finding studies for procedural sedation with patients recovering faster from remimazolam than midazolam. Phase II trials comparing remimazolam to the standard anesthesia protocols for cardiac surgery and colonoscopy were presented at major conferences in October 2014.[13]

A Phase IIa trial comparing remimazolam to midazolam for upper endoscopy was published in December 2014, finding a similar safety profile.[14] Remimazolam was originally synthesized in the late 1990s at Glaxo Wellcome in their labs in Research Triangle Park, North Carolina.[15] [16] [17]

Notes and References

  1. Web site: Byfavo EPAR . European Medicines Agency (EMA) . 9 December 2020 . 20 April 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  2. Web site: Byfavo Product information . Union Register of medicinal products . 3 March 2023.
  3. Kilpatrick GJ, McIntyre MS, Cox RF, Stafford JA, Pacofsky GJ, Lovell GG, Wiard RP, Feldman PL, Collins H, Waszczak BL, Tilbrook GS . 6 . CNS 7056: a novel ultra-short-acting Benzodiazepine . Anesthesiology . 107 . 1 . 60–66 . July 2007 . 17585216 . 10.1097/01.anes.0000267503.85085.c0 . 19504961 . free .
  4. Web site: Byfavo- remimazolam besylate injection, powder, lyophilized, for solution. DailyMed. 20 July 2020. 25 February 2021.
  5. Web site: Drug Trials Snapshots: Byfavo. Food and Drug Administration. 2 July 2020. 25 February 2021.
  6. Cosmo Pharmaceuticals Announces US FDA Approval of Byfavo (remimazolam injection) for the Induction and Maintenance of Procedural Sedation. Cosmo Pharmaceuticals NV. 2 July 2020. 25 February 2021.
  7. Rogers WK, McDowell TS . Remimazolam, a short-acting GABA(A) receptor agonist for intravenous sedation and/or anesthesia in day-case surgical and non-surgical procedures . IDrugs . 13 . 12 . 929–937 . December 2010 . 21154153 .
  8. Saari TI, Uusi-Oukari M, Ahonen J, Olkkola KT . Enhancement of GABAergic activity: neuropharmacological effects of benzodiazepines and therapeutic use in anesthesiology . Pharmacological Reviews . 63 . 1 . 243–267 . March 2011 . 21245208 . 10.1124/pr.110.002717 . 930379 .
  9. Web site: Byfavo: FDA-Approved Drugs. Food and Drug Administration. 25 February 2021.
  10. Web site: Byfavo: Pending EC decision. European Medicines Agency. 29 January 2021. 25 February 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  11. Antonik LJ, Goldwater DR, Kilpatrick GJ, Tilbrook GS, Borkett KM . A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part I. Safety, efficacy, and basic pharmacokinetics . Anesthesia and Analgesia . 115 . 2 . 274–283 . August 2012 . 22190555 . 10.1213/ANE.0b013e31823f0c28 . 21457057 . free .
  12. Worthington MT, Antonik LJ, Goldwater DR, Lees JP, Wilhelm-Ogunbiyi K, Borkett KM, Mitchell MC . A phase Ib, dose-finding study of multiple doses of remimazolam (CNS 7056) in volunteers undergoing colonoscopy . Anesthesia and Analgesia . 117 . 5 . 1093–1100 . November 2013 . 24108261 . 10.1213/ANE.0b013e3182a705ae . 24581168 . free .
  13. Web site: Two Scientific Remimazolam Presentations Are Accepted for ASA and ACG Meeting in October 2014. Oct 1, 2014. 25 February 2021. MarketWired.
  14. Borkett KM, Riff DS, Schwartz HI, Winkle PJ, Pambianco DJ, Lees JP, Wilhelm-Ogunbiyi K . A Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy . Anesthesia and Analgesia . 120 . 4 . 771–780 . April 2015 . 25502841 . 10.1213/ANE.0000000000000548 . 20941788 . free .
  15. Stafford JA, Pacofsky GJ, Cox RF, Cowan JR, Dorsey GF, Gonzales SS, Jung DK, Koszalka GW, McIntyre MS, Tidwell JH, Wiard RP, Feldman PL . 6 . Identification and structure-activity studies of novel ultrashort-acting benzodiazepine receptor agonists . Bioorganic & Medicinal Chemistry Letters . 12 . 21 . 3215–3218 . November 2002 . 12372537 . 10.1016/s0960-894x(02)00512-7 .
  16. Pacofsky GJ, Stafford JA, Cox RF, Cowan JR, Dorsey GF, Gonzales SS, Kaldor I, Koszalka GW, Lovell GG, McIntyre MS, Tidwell JH, Todd D, Whitesell G, Wiard RP, Feldman PL . 6 . Relating the structure, activity, and physical properties of ultrashort-acting benzodiazepine receptor agonists . Bioorganic & Medicinal Chemistry Letters . 12 . 21 . 3219–3222 . November 2002 . 12372538 . 10.1016/s0960-894x(02)00513-9 .
  17. Short-acting benzodiazepines. 2009-01-06. US. 7473689. CeNes Ltd.. Feldman PL, Jung DK, Kaldor I, Pacofsky JG, Stafford JA, Tidwell JH .