Sugammadex

Identification

Name
Sugammadex
Accession Number
DB06206
Type
Small Molecule
Groups
Approved
Description

Sugammadex is a selective relaxant binding agent indicated for reversal of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide during surgery in adults. Rocuronium bromide and vecuronium bromide are neuromuscular blocking medications that cause temporary paralysis and are especially useful for general anesthesia, ventilation, or tracheal intubation that patients may require for surgery. Sugammadex provides a new treatment option to reverse the effects of those medications and possibly help patients recover sooner post-surgery. Sugammadex (brand name Bridion) is marketed by Merck Sharp and Dohme, and was approved by the United States FDA on December 15, 2015.

Structure
Thumb
Synonyms
  • Sugammadex
External IDs
ORG-25969
Product Ingredients
IngredientUNIICASInChI Key
Sugammadex sodiumERJ6X2MXV7343306-79-6KMGKABOMYQLLDJ-UHFFFAOYSA-F
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BridionSolution100 mgIntravenousMerck Ltd.2016-02-19Not applicableCanada
BridionInjection, solution100 mg/1mLIntravenousMerck Sharp & Dohme Corp.2015-12-15Not applicableUs
BridionInjection, solution100 mg/1mLIntravenousMerck Sharp & Dohme Corp.2015-12-15Not applicableUs
Categories
UNII
361LPM2T56
CAS number
343306-71-8
Weight
Average: 2002.12
Monoisotopic: 2000.408874758
Chemical Formula
C72H112O48S8
InChI Key
WHRODDIHRRDWEW-VTHZAVIASA-N
InChI
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
IUPAC Name
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-carboxyethyl)sulfanyl]methyl})-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]methyl}sulfanyl)propanoic acid
SMILES
O[C@@H]1[C@@H](O)[C@@H]2O[C@H]3O[C@H](CSCCC(O)=O)[C@@H](O[C@H]4O[C@H](CSCCC(O)=O)[C@@H](O[C@H]5O[C@H](CSCCC(O)=O)[C@@H](O[C@H]6O[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](O[C@H]1O[C@@H]2CSCCC(O)=O)[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

Pharmacology

Indication

Sugammadex is indicated for the reversal of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide in adults undergoing surgery.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Sugammadex is a modified gamma-cyclodextrin which forms very tight water soluble complexes at a 1:1 ratio with steroidal neuromuscular blocking drugs (rocuronium > vecuronium >> pancuronium). Sugammadex creates a concentration gradient which favors movement of rocurionium from the neuromuscular junction into the plasma, which quickly reverses rocuronium-induced neuromuscular blockade. The free rocuronium in the plasma are then bound tightly to sugammadex, assisting the diffusion of the remaining rocuronium molecules out of the neuromuscular junction and increasing bound and free rocuronium in the plasma.

Absorption

Sugammadex is administered intravenously.

Volume of distribution

At steady state, the volume of distribution is 11-14 L in adult patients with normal renal function.

Protein binding

Sugammadex does not bind plasma proteins.

Metabolism

No metabolites of sugammadex were observed during clinical studies.

Route of elimination

Renal excretion of unchanged product. >90 of dose is excreted within 24 hours. 0.02% is excreted in feces and air.

Half life

About 2 hours

Clearance

88L/min

Toxicity

Patients with severe renal impairment (with creatinine clearance below 30 mL/min) should avoid use of drug as their clearance of the drug is reduced and there is inconsistent evidence about its safety in this subset of patients.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding and hemorrhage can be increased when (R)-warfarin is combined with Sugammadex.
(S)-WarfarinThe risk or severity of bleeding and hemorrhage can be increased when (S)-Warfarin is combined with Sugammadex.
4-hydroxycoumarinThe risk or severity of bleeding and hemorrhage can be increased when 4-hydroxycoumarin is combined with Sugammadex.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Abciximab is combined with Sugammadex.
AcenocoumarolThe risk or severity of bleeding and hemorrhage can be increased when Acenocoumarol is combined with Sugammadex.
Acetylsalicylic acidThe risk or severity of bleeding and hemorrhage can be increased when Acetylsalicylic acid is combined with Sugammadex.
AlteplaseThe risk or severity of bleeding and hemorrhage can be increased when Alteplase is combined with Sugammadex.
AmediplaseThe risk or severity of bleeding and hemorrhage can be increased when Amediplase is combined with Sugammadex.
AnagrelideThe risk or severity of bleeding and hemorrhage can be increased when Anagrelide is combined with Sugammadex.
AncrodThe risk or severity of bleeding and hemorrhage can be increased when Ancrod is combined with Sugammadex.
Food Interactions
No interactions found.

References

General References
  1. Naguib M: Sugammadex: another milestone in clinical neuromuscular pharmacology. Anesth Analg. 2007 Mar;104(3):575-81. [PubMed:17312211]
  2. Schaller SJ, Fink H: Sugammadex as a reversal agent for neuromuscular block: an evidence-based review. Core Evid. 2013;8:57-67. doi: 10.2147/CE.S35675. Epub 2013 Sep 25. [PubMed:24098155]
  3. Nag K, Singh DR, Shetti AN, Kumar H, Sivashanmugam T, Parthasarathy S: Sugammadex: A revolutionary drug in neuromuscular pharmacology. Anesth Essays Res. 2013 Sep-Dec;7(3):302-6. doi: 10.4103/0259-1162.123211. [PubMed:25885973]
External Links
KEGG Drug
D05940
PubChem Compound
6918585
PubChem Substance
347827763
ChemSpider
32689915
ChEBI
90953
ChEMBL
CHEMBL2111107
Wikipedia
Sugammadex
ATC Codes
V03AB35 — Sugammadex
AHFS Codes
  • 92:12.00 — Antidotes
FDA label
Download (354 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingPreventionIncidence of Postoperative Residual Curarization1
1CompletedTreatmentAnaphylactic-type reactions / Hypersensitivity1
1CompletedTreatmentHypersensitivity1
1CompletedTreatmentImpaired Renal Function1
1RecruitingTreatmentHigh-Frequency Jet Ventilation / Vocal Cord Resection1
2CompletedNot AvailableObesity, Morbid1
2CompletedTreatmentMorbidly Obese Patients1
2CompletedTreatmentAdjunct to general anesthesia therapy6
2Not Yet RecruitingPreventionCurarization, Postoperative Residual2
2, 3CompletedTreatmentOrganophosphate Poisoning1
2, 3Not Yet RecruitingTreatmentAnaesthesia therapy / Beta-Thalassemia / Hepatic Metastases / Pediatric Cancer / Pediatric Hepatoblastoma / Pediatric Tumor1
2, 3Unknown StatusTreatmentNeuromuscular Blockade / Obesity, Morbid1
3Active Not RecruitingTreatmentMinor burns1
3CompletedPreventionPost-Operative Nausea and Vomiting (PONV)1
3CompletedTreatmentAnaesthesia therapy4
3CompletedTreatmentAnaesthesia therapy / Neuromuscular Blockade1
3CompletedTreatmentAntithrombotic Agents / Arthroplasty, Replacement, Hip / Arthroplasty, Replacement, Knee / Coagulation, Blood / Neuromuscular Blockade1
3CompletedTreatmentDiaphragmatic Dysfunction / Muscle Fatigue / Muscle Weakness1
3CompletedTreatmentNeuromuscular Blockade5
3CompletedTreatmentAdjunct to general anesthesia therapy / Neuromuscular Blockade2
3CompletedTreatmentPostoperative Neuromuscular Block1
3CompletedTreatmentSurgical Procedures, Elective1
3CompletedTreatmentAdjunct to general anesthesia therapy10
3RecruitingTreatmentGeneral Surgery1
3Unknown StatusNot AvailableNeuromuscular Blockade1
4Active Not RecruitingPreventionNeuromuscular Blockade / Postoperative Complications1
4Active Not RecruitingSupportive CareMuscle Relaxation1
4CompletedNot AvailableInjury to Nerve During Surgery1
4CompletedNot AvailableLaparoscopy / Neuromuscular Blockade / Pneumoperitoneum / Rating Scales / Surgical Conditions1
4CompletedBasic ScienceElectromyography / Respiratory Muscles1
4CompletedDiagnosticIntraocular Pressure Changes During Tracheal Extubation1
4CompletedOtherNeuromuscular Blockade3
4CompletedPreventionIncidence of Postoperative Nausea and Vomiting1
4CompletedScreeningAnesthesia; Functional1
4CompletedScreeningSpinal Curvatures1
4CompletedTreatmentAnaesthesia1
4CompletedTreatmentAnaesthesia therapy1
4CompletedTreatmentAnesthesia Recovery1
4CompletedTreatmentBrain Cancer1
4CompletedTreatmentCaesarean Sections / Pregnancy1
4CompletedTreatmentChronic Renal Failure (CRF) / Neuromuscular Blockade1
4CompletedTreatmentCirrhosis and Chronic Liver Disease1
4CompletedTreatmentComplication of Ventilation Therapy / Observation of Neuromuscular Block / Postoperative Recovery1
4CompletedTreatmentGallbladder disorders1
4CompletedTreatmentIncomplete Reversal of Neuromuscular Block1
4CompletedTreatmentIntubation, Endotracheal1
4CompletedTreatmentLaparoscopic Herniotomy1
4CompletedTreatmentMajor Abdominal Surgery1
4CompletedTreatmentNeuromuscular Block1
4CompletedTreatmentNeuromuscular Blockade2
4CompletedTreatmentObstructive Sleep Apnea (OSA)1
4CompletedTreatmentPostoperative Respiratory Condition1
4CompletedTreatmentPre-eclampsia Aggravated1
4CompletedTreatmentRespiratory-Gated Imaging Techniques1
4CompletedTreatmentReversal of Skeletal Muscle Relaxant / Underdosing of Skeletal Muscle Relaxants for Laparotomy1
4CompletedTreatmentSpine Surgery1
4CompletedTreatmentUnderdosing of Other General Anesthetics1
4Enrolling by InvitationTreatmentGeneral Surgery1
4Enrolling by InvitationTreatmentNeuromuscular Blockade1
4Not Yet RecruitingDiagnosticResidual Neuromuscular Blockade1
4Not Yet RecruitingPreventionPulmonary Complications1
4Not Yet RecruitingTreatmentGeneral Surgery / Postoperative pain1
4Not Yet RecruitingTreatmentGynecology / Surgery, Laparoscopic1
4Not Yet RecruitingTreatmentLaryngoscopic Surgical Procedures1
4Not Yet RecruitingTreatmentNeuromuscular Block1
4Not Yet RecruitingTreatmentNeuromuscular Block / Postoperative Residual Curarization1
4Not Yet RecruitingTreatmentObstructive Sleep Apnea (OSA)1
4Not Yet RecruitingTreatmentRespiratory Insufficiency1
4RecruitingOtherNeuromuscular Blockade1
4RecruitingPreventionEmergence Delirium1
4RecruitingPreventionLaparoscopic Sleeve Gastrectomy / Post-Operative Nausea and Vomiting (PONV)1
4RecruitingSupportive CareBladder Cancers / Malignant Neoplasms of Urinary Tract1
4RecruitingSupportive CareCoronary Artery Bypass Graft Surgery Patients / Coronary Artery Bypass Graft, Aortic Valve Replacement or Coronary Artery Bypass Graft-Aortic Valve Replacement Combination Surgery / Post CABG Extubation1
4RecruitingTreatmentAnaesthesia therapy / Neuromuscular Blockade1
4RecruitingTreatmentAnesthesia Recovery Period / Laparoscopy1
4RecruitingTreatmentAnesthesiology Management1
4RecruitingTreatmentAdjunct to general anesthesia therapy / Hip Fractures / Neuromuscular Blockade / Spinal Anaesthesia1
4RecruitingTreatmentMalignant Neoplasms of Digestive Organs / Malignant Neoplasms of Female Genital Organs / Malignant Neoplasms of Male Genital Organs / Malignant Neoplasms of Urinary Tract1
4RecruitingTreatmentMicrolaryngoscopy / Rigid Bronchoscopy1
4RecruitingTreatmentNeuromuscular Block1
4RecruitingTreatmentNeuromuscular Blockade3
4RecruitingTreatmentNeuromuscular Blockade / Respiratory Insufficiency1
4RecruitingTreatmentPost-Operative Nausea and Vomiting (PONV) / Respiratory Conditions Due to Other External Agents1
4RecruitingTreatmentPost-operative Residual Curarization1
4RecruitingTreatmentPosterior Cervical Decompression and Fusion / Posterior Cervical Spine Surgery1
4RecruitingTreatmentReversal of Neuromuscular Blockade1
4RecruitingTreatmentTime of a TOF Ratio >0,91
4Unknown StatusSupportive CareAnesthesia Recovery Period1
4Unknown StatusTreatmentAdult Subjects Undergoing Abdominal Surgery Under General Anesthesia1
4Unknown StatusTreatmentNeuromuscular Blockade1
4WithdrawnNot AvailableNeuromuscular Blockade1
Not AvailableActive Not RecruitingNot AvailableNeuromuscular Blockade1
Not AvailableCompletedNot AvailableAnesthesia Recovery Period, Neuromuscular Blockade1
Not AvailableCompletedNot AvailableNeuromuscular Blockade2
Not AvailableCompletedNot AvailableNeuromuscular Monitoring After Administration of Neuromuscular Blocking Agents in Different Types of Surgery1
Not AvailableCompletedNot AvailablePostoperative Residual Paralysis1
Not AvailableCompletedNot AvailableResidual Neuromuscular Block (TOF-ratio of 0.2)1
Not AvailableCompletedHealth Services ResearchMuscle Relaxation1
Not AvailableCompletedOtherAnesthesiology Management1
Not AvailableCompletedPreventionElderly Patients Undergoing Trans Pars Plana Vitrectomy With General Anesthesia1
Not AvailableCompletedScreeningPost Operative Cognitive Dysfunction1
Not AvailableCompletedSupportive CareResidual Neuromuscular Block1
Not AvailableCompletedSupportive CareRobot-Assisted Laparoscopic Radical Prostatectomy1
Not AvailableCompletedTreatmentFasciculations / Intubating Conditions / Patients Satisfaction / Postoperative Myalgia / Throat Pain1
Not AvailableCompletedTreatmentNeuromuscular Blockade1
Not AvailableCompletedTreatmentAdjunct to general anesthesia therapy1
Not AvailableEnrolling by InvitationSupportive CareSupratentorial Brain Tumor Surgery1
Not AvailableNot Yet RecruitingPreventionThyroid Surgery1
Not AvailableRecruitingNot AvailableDelirium1
Not AvailableRecruitingNot AvailableOutcome, Fatal1
Not AvailableRecruitingNot AvailableResidual Neuromuscular Blockade1
Not AvailableRecruitingDiagnosticBlood Coagulation Tests ( INR, APTT)1
Not AvailableRecruitingOtherBMI >30 kg/m2 / Malignant Neoplasm of Stomach1
Not AvailableRecruitingOtherPostoperative Residual Curarization / Transplantation, Liver1
Not AvailableUnknown StatusTreatmentObesity, Morbid1
Not AvailableUnknown StatusTreatmentSurgical Procedure, Unspecified1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionIntravenous100 mg/1mL
SolutionIntravenous100 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7265009No2007-09-042020-08-07Us
US7265099No2007-09-042020-08-07Us
US6949527No2005-09-272021-01-27Us
USRE44733No2014-01-282021-01-27Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility26.6 mg/mLALOGPS
logP-0.69ALOGPS
logP-5.4ChemAxon
logS-1.9ALOGPS
pKa (Strongest Acidic)2.82ChemAxon
Physiological Charge-8ChemAxon
Hydrogen Acceptor Count48ChemAxon
Hydrogen Donor Count24ChemAxon
Polar Surface Area769.76 Å2ChemAxon
Rotatable Bond Count40ChemAxon
Refractivity432.64 m3·mol-1ChemAxon
Polarizability189.62 Å3ChemAxon
Number of Rings9ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as oligosaccharides. These are carbohydrates made up of 3 to 10 monosaccharide units linked to each other through glycosidic bonds.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Oligosaccharides
Alternative Parents
Oxanes / Secondary alcohols / Sulfenyl compounds / Polyols / Oxacyclic compounds / Dialkylthioethers / Carboxylic acids / Acetals / Organic oxides / Hydrocarbon derivatives
show 1 more
Substituents
Oligosaccharide / Oxane / Secondary alcohol / Acetal / Carboxylic acid derivative / Carboxylic acid / Polyol / Oxacycle / Thioether / Organoheterocyclic compound
show 8 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
Not Available

Drug created on March 19, 2008 10:17 / Updated on December 14, 2018 17:10