SUGAMMADEX

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C72H112O48S8
Molecular Weight	2002.151
Optical Activity	UNSPECIFIED
Defined Stereocenters	40 / 40
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12O[C@H](CSCCC(O)=O)[C@@H](O[C@@]3([H])O[C@H](CSCCC(O)=O)[C@@H](O[C@@]4([H])O[C@H](CSCCC(O)=O)[C@@H](O[C@@]5([H])O[C@H](CSCCC(O)=O)[C@@H](O[C@@]6([H])O[C@H](CSCCC(O)=O)[C@@]([H])(O[C@H]7O[C@H](CSCCC(O)=O)[C@@]([H])(O[C@H]8O[C@H](CSCCC(O)=O)[C@@]([H])(O[C@H]9O[C@H](CSCCC(O)=O)[C@@H](O1)[C@H](O)[C@H]9O)[C@H](O)[C@H]8O)[C@H](O)[C@H]7O)[C@H](O)[C@H]6O)[C@H](O)[C@H]5O)[C@H](O)[C@H]4O)[C@H](O)[C@H]3O)[C@H](O)[C@H]2O

InChI

InChIKey=WHRODDIHRRDWEW-VTHZAVIASA-N

InChI=1S/C72H112O48S8/c73-33(74)1-9-121-17-25-57-41(89)49(97)65(105-25)114-58-26(18-122-10-2-34(75)76)107-67(51(99)43(58)91)116-60-28(20-124-12-4-36(79)80)109-69(53(101)45(60)93)118-62-30(22-126-14-6-38(83)84)111-71(55(103)47(62)95)120-64-32(24-128-16-8-40(87)88)112-72(56(104)48(64)96)119-63-31(23-127-15-7-39(85)86)110-70(54(102)46(63)94)117-61-29(21-125-13-5-37(81)82)108-68(52(100)44(61)92)115-59-27(19-123-11-3-35(77)78)106-66(113-57)50(98)42(59)90/h25-32,41-72,89-104H,1-24H2,(H,73,74)(H,75,76)(H,77,78)(H,79,80)(H,81,82)(H,83,84)(H,85,86)(H,87,88)/t25-,26-,27-,28-,29-,30-,31-,32-,41-,42-,43-,44-,45-,46-,47-,48-,49-,50-,51-,52-,53-,54-,55-,56-,57-,58-,59-,60-,61-,62-,63-,64-,65-,66-,67-,68-,69-,70-,71-,72-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11960492
Curator's Comment: Description was created based on several sources, including https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022225lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/25885973

Sugammadex (ORG 25969) is a cyclodextrin derivative was synthesized as synthetic receptor (or host molecule) for neuromuscular blockers (rocuronium and vecuronium). It forms a complex with the neuromuscular blocking agents rocuronium and vecuronium, and it reduces the amount of neuromuscular blocking agent available to bind to nicotinic cholinergic receptors in the neuromuscular junction. This results in the reversal of neuromuscular blockade induced by rocuronium and vecuronium. The clinical use of sugammadex promises to eliminate many of the shortcomings in current anesthetic practice with regard to antagonism of rocuronium and other aminosteroid muscle relaxants. Sugammadex is indicated for the reversal of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide in adults undergoing surgery.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
CHEMBL1201244: ROCURONIUM 2 Target ID: CHEMBL1201244: ROCURONIUM Sources: https://www.ncbi.nlm.nih.gov/pubmed/11960492 \| https://www.ncbi.nlm.nih.gov/pubmed/19104176	Binding Agent 1064
CHEMBL1201219: VECURONIUM 2 Target ID: CHEMBL1201219: VECURONIUM Sources: https://www.ncbi.nlm.nih.gov/pubmed/19104176	Binding Agent 1064

Conditions

Condition	Modality	Targets	Highest Phase	Product
Neuromuscular blockade 5 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022225lbl.pdf http://adis.springer.com/drugs/800016367	Preventing		Approved 8429	BRIDION Approved Use BRIDION (sugammadex) is indicated for the reversal of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide in adults undergoing surgery Launch Date 2015

C_max

Value	Dose	Analyte	Population
66.1 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02011490	4 mg/kg single, intravenous bolus dose: 4 mg/kg route of administration: intravenous bolus experiment type: single co-administered:	SUGAMMADEX plasma	Homo sapiens population: healthy age: sex: food status:
60.6 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02011490	4 mg/kg single, intravenous bolus dose: 4 mg/kg route of administration: intravenous bolus experiment type: single co-administered:	SUGAMMADEX plasma	Homo sapiens population: unhealthy age: sex: food status:
62.2 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02011490	4 mg/kg single, intravenous bolus dose: 4 mg/kg route of administration: intravenous bolus experiment type: single co-administered:	SUGAMMADEX plasma	Homo sapiens population: unhealthy age: sex: food status:

AUC

Value	Dose	Analyte	Population
61.1 ug*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02011490	4 mg/kg single, intravenous bolus dose: 4 mg/kg route of administration: intravenous bolus experiment type: single co-administered:	SUGAMMADEX plasma	Homo sapiens population: healthy age: sex: food status:
148 ug*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02011490	4 mg/kg single, intravenous bolus dose: 4 mg/kg route of administration: intravenous bolus experiment type: single co-administered:	SUGAMMADEX plasma	Homo sapiens population: unhealthy age: sex: food status:
335 ug*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02011490	4 mg/kg single, intravenous bolus dose: 4 mg/kg route of administration: intravenous bolus experiment type: single co-administered:	SUGAMMADEX plasma	Homo sapiens population: unhealthy age: sex: food status:

Doses

Dose	Population	Adverse events
96 mg/kg single, intravenous Highest studied dose Dose: 96 mg/kg Route: intravenous Route: single Dose: 96 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/20825252	healthy, 18-65 years n = 12 Health Status: healthy Age Group: 18-65 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/20825252	Other AEs: Dysgeusia, Headache... Other AEs: Dysgeusia (66.7%) Headache (16.7%) Fatigue (16.7%) Nausea (16.7%) Dizziness postural (8.3%) Abdominal pain (8.3%) Pharyngolaryngeal pain (16.7%) Micturition urgency (8.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/20825252
16 mg/kg single, intravenous Recommended Dose: 16 mg/kg Route: intravenous Route: single Dose: 16 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66	unhealthy n = 496 Health Status: unhealthy Population Size: 496 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66	Disc. AE: Anaphylactic shock... AEs leading to discontinuation/dose reduction: Anaphylactic shock (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66
4 mg/kg single, intravenous Recommended Dose: 4 mg/kg Route: intravenous Route: single Dose: 4 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66	unhealthy n = 1505 Health Status: unhealthy Population Size: 1505 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66	Disc. AE: Hypersensitivity reaction... AEs leading to discontinuation/dose reduction: Hypersensitivity reaction (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66
32 mg/kg single, intravenous Dose: 32 mg/kg Route: intravenous Route: single Dose: 32 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66	unhealthy n = 165 Health Status: unhealthy Population Size: 165 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66	Disc. AE: Hypersensitivity reaction... AEs leading to discontinuation/dose reduction: Hypersensitivity reaction (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66
8 mg/kg single, intravenous Dose: 8 mg/kg Route: intravenous Route: single Dose: 8 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66	unhealthy n = 156 Health Status: unhealthy Population Size: 156 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66	Disc. AE: Tachycardia... AEs leading to discontinuation/dose reduction: Tachycardia (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66

AEs

AE	Significance	Dose	Population
Fatigue	16.7%	96 mg/kg single, intravenous Highest studied dose Dose: 96 mg/kg Route: intravenous Route: single Dose: 96 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/20825252	healthy, 18-65 years n = 12 Health Status: healthy Age Group: 18-65 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/20825252
Headache	16.7%	96 mg/kg single, intravenous Highest studied dose Dose: 96 mg/kg Route: intravenous Route: single Dose: 96 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/20825252	healthy, 18-65 years n = 12 Health Status: healthy Age Group: 18-65 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/20825252
Nausea	16.7%	96 mg/kg single, intravenous Highest studied dose Dose: 96 mg/kg Route: intravenous Route: single Dose: 96 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/20825252	healthy, 18-65 years n = 12 Health Status: healthy Age Group: 18-65 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/20825252
Pharyngolaryngeal pain	16.7%	96 mg/kg single, intravenous Highest studied dose Dose: 96 mg/kg Route: intravenous Route: single Dose: 96 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/20825252	healthy, 18-65 years n = 12 Health Status: healthy Age Group: 18-65 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/20825252
Dysgeusia	66.7%	96 mg/kg single, intravenous Highest studied dose Dose: 96 mg/kg Route: intravenous Route: single Dose: 96 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/20825252	healthy, 18-65 years n = 12 Health Status: healthy Age Group: 18-65 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/20825252
Abdominal pain	8.3%	96 mg/kg single, intravenous Highest studied dose Dose: 96 mg/kg Route: intravenous Route: single Dose: 96 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/20825252	healthy, 18-65 years n = 12 Health Status: healthy Age Group: 18-65 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/20825252
Dizziness postural	8.3%	96 mg/kg single, intravenous Highest studied dose Dose: 96 mg/kg Route: intravenous Route: single Dose: 96 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/20825252	healthy, 18-65 years n = 12 Health Status: healthy Age Group: 18-65 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/20825252
Micturition urgency	8.3%	96 mg/kg single, intravenous Highest studied dose Dose: 96 mg/kg Route: intravenous Route: single Dose: 96 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/20825252	healthy, 18-65 years n = 12 Health Status: healthy Age Group: 18-65 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/20825252
Anaphylactic shock	1 patient Disc. AE	16 mg/kg single, intravenous Recommended Dose: 16 mg/kg Route: intravenous Route: single Dose: 16 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66	unhealthy n = 496 Health Status: unhealthy Population Size: 496 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66
Hypersensitivity reaction	1 patient Disc. AE	4 mg/kg single, intravenous Recommended Dose: 4 mg/kg Route: intravenous Route: single Dose: 4 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66	unhealthy n = 1505 Health Status: unhealthy Population Size: 1505 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66
Hypersensitivity reaction	1 patient Disc. AE	32 mg/kg single, intravenous Dose: 32 mg/kg Route: intravenous Route: single Dose: 32 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66	unhealthy n = 165 Health Status: unhealthy Population Size: 165 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66
Tachycardia	1 patient Disc. AE	8 mg/kg single, intravenous Dose: 8 mg/kg Route: intravenous Route: single Dose: 8 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66	unhealthy n = 156 Health Status: unhealthy Population Size: 156 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000MedR.pdf Page: p. 66

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022225Orig1s000PharmR.pdf#page=198 Page: 198.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:90953	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:90953
ChemicalBook	CB71011756	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB71011756
MolPort	MolPort-046-424-800	https://www.molport.com/shop/molecule-link/MolPort-046-424-800

PubMed

Title	Date	PubMed
Cyclodextrin-derived host molecules as reversal agents for the neuromuscular blocker rocuronium bromide: synthesis and structure-activity relationships.	2002 Apr 25	11960492
Neostigmine but not sugammadex impairs upper airway dilator muscle activity and breathing.	2008 Sep	18559352
Discovery, development, and clinical application of sugammadex sodium, a selective relaxant binding agent.	2009 Feb 6	19920893
Pharmacokinetic-pharmacodynamic model for the reversal of neuromuscular blockade by sugammadex.	2009 Jan	19104176
Sugammadex, a neuromuscular blockade reversal agent, causes neuronal apoptosis in primary cultures.	2013	23983586
Sugammadex: A revolutionary drug in neuromuscular pharmacology.	2013 Sep-Dec	25885973

Patents

Sample Use Guides

In Vivo Use Guide

BRIDION (sugammadex) can be used to reverse different levels of rocuronium- or vecuronium-induced neuromuscular blockade. For rocuronium and vecuronium: • A dose of 4 mg/kg BRIDION is recommended if spontaneous recovery of the twitch response has reached 1 to 2 post-tetanic counts (PTC) and there are no twitch responses to train-of-four (TOF) stimulation following rocuronium- or vecuronium-induced neuromuscular blockade. • A dose of 2 mg/kg BRIDION is recommended if spontaneous recovery has reached the reappearance of the second twitch (T2) in response to TOF stimulation following rocuronium- or vecuronium-induced neuromuscular blockade. For rocuronium only: • A dose of 16 mg/kg BRIDION is recommended if there is a clinical need to reverse neuromuscular blockade soon (approximately 3 minutes) after administration of a single dose of 1.2 mg/kg of rocuronium. The efficacy of the 16 mg/kg dose of BRIDION following administration of vecuronium has not been studied.

Route of Administration: Intravenous

In Vitro Use Guide

75 ug/ml sugammadex causes apoptotic/necrosis neuron death in primary cultures.

Name

Type

Language

SUGAMMADEX

Official Name

English

.GAMMA.-CYCLODEXTRIN, 6A,6B,6C,6D,6E,7F,6G,6H-OCTAKIS-S-(2-CARBOXYETHYL)-6A,6B,6C,6D,6E,7F,6G,6H-OCTATHIO-

Common Name

English

Sugammadex [WHO-DD]

Common Name

English

6,6',6'',6''',6'''',6''''',6'''''',6'''''''-OCTAKIS-S-(2-CARBOXYLATOETHYL)-6,6',6'',6''',6'''',6''''',6'''''',6'''''''-OCTATHIOCYCLO-.ALPHA.-(1->4)-D-OCTAGLUCOPYRANOSIDE

Common Name

English

SUGAMMADEX [USAN]

Common Name

English

SUGAMMADEX [EMA EPAR]

Common Name

English

SUGAMMADEX [MI]

Common Name

English

sugammadex [INN]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QV03AB35