Sugammadex

Overview

Sugammadex, sold under the brand name Bridion, is a medication for the reversal of neuromuscular blockade induced by rocuronium and vecuronium in general anaesthesia. It is the first selective relaxant binding agent (SRBA). It is marketed by Merck.[1][2] WP

The most common side effects include cough, airway problems due to the anaesthesia wearing off, reduced blood pressure and other complications such as changes in heart rate.[3] WP

Sugammadex is available as a generic medication.[4] WP

Uses, dosage and effects

Medical uses

Sugammadex is indicated for the reversal of neuromuscular blockade induced by rocuronium or vecuronium.[1][3] WP

Pharmacology

Pharmacodynamics

Sugammadex is a modified γ-cyclodextrin, with a lipophilic core and a hydrophilic periphery. This gamma cyclodextrin has been modified from its natural state by placing eight carboxyl thio ether groups at the sixth carbon positions. These extensions extend the cavity size allowing greater encapsulation of the rocuronium molecule. These negatively charged extensions electrostatically bind to the quaternary nitrogen of the target as well as contribute to the aqueous nature of the cyclodextrin. Sugammadex's binding encapsulation of rocuronium is one of the strongest among cyclodextrins and their guest molecules. The rocuronium molecule (a modified steroid) bound within sugammadex's lipophilic core, is rendered unavailable to bind to the acetylcholine receptor at the neuromuscular junction. WP⚠ A table follows this text in the source and is not copied here. Open the source to see it.

Left: Schematic of a sugammadex molecule encapsulating a rocuronium molecule. Right: Space-filling model of a sugammadex sodium molecule in the same orientation. WP

Sugammadex, unlike neostigmine, does not inhibit acetylcholinesterase so cholinergic effects are not produced and co-administration of an antimuscarinic agent (glycopyrronium bromide or atropine) is not needed. Sugammadex might therefore be expected to have fewer adverse effects than the traditional reversal agents. WP

When muscle relaxant with rapid onset and short duration of action is required, there has been little choice apart from succinylcholine but this drug has important contraindications; for example, it can trigger malignant hyperthermia in susceptible individuals, it has a prolonged duration of action in patients with pseudocholinesterase deficiency and it causes an increase in plasma potassium concentration which is dangerous in some circumstances. Rocuronium has a comparably quick onset in high dose (0.6 mg kg⁻¹ to 1 mg kg⁻¹) and can be rapidly reversed with sugammadex (16 mg kg⁻¹), so this drug combination offers an alternative to suxamethonium. WP

'Recurarisation', a phenomenon of recurrence of neuromuscular block, may occur where the reversal agents wear off before a neuromuscular blocking drug is completely cleared. This is very unusual with all but the longest acting neuromuscular blocking drugs (such as gallamine, pancuronium or tubocurarine). It has been demonstrated to occur only rarely with sugammadex, and only when insufficient doses were administered. The underlying mechanism is thought to be related to redistribution of relaxant after reversal. It may occur for a limited range of sugammadex doses which are sufficient for complex formation with relaxant in the central compartment, but insufficient for additional relaxant returning to central from peripheral compartments.[5][6] WP

Sugammadex has been shown to have affinity for two other aminosteroid neuromuscular blocking agents, vecuronium and pancuronium. Although sugammadex has a lower affinity for vecuronium than for rocuronium, reversal of vecuronium is still effective because fewer vecuronium molecules are present in vivo for equivalent blockade: vecuronium is approximately seven times more potent than rocuronium. Sugammadex encapsulates with a 1:1 ratio and therefore will adequately reverse vecuronium as there are fewer molecules to bind compared to rocuronium. Shallow pancuronium blockade has been successfully reversed by sugammadex in phase III clinical trials.[7][8] WP

History

History

Sugammadex was discovered by the pharmaceutical company Organon at the Newhouse Research Site in Scotland. Organon was acquired by Schering-Plough in 2007; Schering-Plough merged with Merck in 2009. Sugammadex is now owned and sold by Merck.[9] WP

The US Food and Drug Administration (FDA) initially rejected Schering-Plough's New Drug Application for sugammadex in 2008, but finally approved the medication for use in the United States in December 2015. Sugammadex was approved for use in the European Union in July 2008.[3][10–13] WP

Chemistry

Formula

C72H112O48S8 PC

CAS number

343306-71-8 PC

Molar mass (g/mol)

2002.2 PC

IUPAC name (computed by PubChem)

3-[[(1S,3S,5S,6S,8S,10S,11S,13S,15S,16S,18S,20S,21S,23S,25S,26S,28S,30S,31S,33S,35S,36S,38S,40S,41R,42R,43R,44R,45R,46R,47R,48R,49R,50R,51R,52R,53R,54R,55R,56R)-10,15,20,25,30,35,40-heptakis(2-carboxyethylsulfanylmethyl)-41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56-hexadecahydroxy-2,4,7,9,12,14,17,19,22,24,27,29,32,34,37,39-hexadecaoxanonacyclo[36.2.2.23,6.28,11.213,16.218,21.223,26.228,31.233,36]hexapentacontan-5-yl]methylsulfanyl]propanoic acid PC

SMILES

C(CSC[C@@H]1[C@@H]2[C@@H]([C@H]([C@H](O1)O[C@@H]3[C@H](O[C@@H]([C@@H]([C@H]3O)O)O[C@@H]4[C@H](O[C@@H]([C@@H]([C@H]4O)O)O[C@@H]5[C@H](O[C@@H]([C@@H]([C@H]5O)O)O[C@@H]6[C@H](O[C@@H]([C@@H]([C@H]6O)O)O[C@@H]7[C@H](O[C@@H]([C@@H]([C@H]7O)O)O[C@@H]8[C@H](O[C@@H]([C@@H]([C@H]8O)O)O[C@@H]9[C@H](O[C@H](O2)[C@@H]([C@H]9O)O)CSCCC(=O)O)CSCCC(=O)O)CSCCC(=O)O)CSCCC(=O)O)CSCCC(=O)O)CSCCC(=O)O)CSCCC(=O)O)O)O)C(=O)O PC

InChIKey

WHRODDIHRRDWEW-VTHZAVIASA-N PC

PubChem CID

6918585

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Bridion- sugammadex injection, solution. 14 December 2018
2. Other Dosing for Bridion (sugammadex)
3. Journal / agency Bridion EPAR. 17 September 2018
4. Journal / agency Sugammadex Adroiq. 16 June 2023
5. Journal / agency Miller RD. Sugammadex: an opportunity to change the practice of anesthesiology?. Anesthesia and Analgesia. March 2007. doi:10.1213/01.ane.0000255645.64583.e8 · PMID 17312188
6. Journal / agency Eleveld DJ, Kuizenga K, Proost JH, Wierda JM. A temporary decrease in twitch response during reversal of rocuronium-induced muscle relaxation with a small dose of sugammadex. Anesthesia and Analgesia. March 2007. doi:10.1213/01.ane.0000250617.79166.7f · PMID 17312212
7. Journal / agency Welliver M. New drug sugammadex: a selective relaxant binding agent. AANA Journal. October 2006. PMID 17048555
8. Other Decoopman M (2007). "Reversal of pancuronium-induced block by the selective relaxant binding agent sugammadex". Eur J Anaesthesiol. 24(Suppl 39):110-111
9. Journal / agency Naguib M. Sugammadex: another milestone in clinical neuromuscular pharmacology. Anesthesia and Analgesia. March 2007. doi:10.1213/01.ane.0000244594.63318.fc · PMID 17312211
10. Other U.S. FDA Issues Action Letter for Sugammadex. 2008-08-01
11. Journal / agency Bridion (sugammadex) Injection. 4 February 2016
12. Journal / agency FDA approves Bridion to reverse effects of neuromuscular blocking drugs used during surgery. 2015-12-15
13. Other Bridion (sugammadex) Injection - First and Only Selective Relaxant Binding Agent - Approved in European Union. 2008-07-29

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.