Avibactam sodium

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C7H10N3O6S.Na
Molecular Weight	287.226
Optical Activity	( - )
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].NC(=O)[C@@H]1CC[C@@H]2C[N@]1C(=O)N2OS([O-])(=O)=O

InChI

InChIKey=RTCIKUMODPANKX-JBUOLDKXSA-M

InChI=1S/C7H11N3O6S.Na/c8-6(11)5-2-1-4-3-9(5)7(12)10(4)16-17(13,14)15;/h4-5H,1-3H2,(H2,8,11)(H,13,14,15);/q;+1/p-1/t4-,5+;/m1./s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206494s002lbl.pdf | https://www.future-science.com/doi/full/10.4155/fmc-2016-0078 | https://www.ncbi.nlm.nih.gov/pubmed/22753474 | https://www.ncbi.nlm.nih.gov/pubmed/15254025 | https://www.ncbi.nlm.nih.gov/pubmed/23371303

Avibactam (formerly NXL104, AVE1330A) is a synthetic non-β-lactam, covalent, slowly reversible β-lactamase inhibitor that inhibits the activities of Ambler class A and C β-lactamases and some Ambler class D enzymes. The combination of ceftazidime with avibactam exhibited broad-spectrum activity against Ambler class A- and class C-producing Enterobacteriaceae. AVYCAZ is a combination of ceftazidime, a cephalosporin, and avibactam indicated for the treatment of patients with the following infections caused by designated susceptible microorganisms: Complicated Intra-abdominal Infections, used in combination with metronidazole and Complicated Urinary Tract Infections, including Pyelonephritis.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial beta-lactamase TEM 11 Target ID: CHEMBL2364670 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23371303	Inhibitor 8504		8.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Complicated Intra-abdominal Infections 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23371303 https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206494s002lbl.pdf	Curative		Approved 8583	AVYCAZ Approved Use AVYCAZ is a combination of ceftazidime, a cephalosporin, and avibactam, a beta-lactamase inhibitor, indicated for the treatment of patients 18 years or older with the following infections caused by designated susceptible microorganisms: complicated Intra-abdominal Infections (cIAI), used in combination with metronidazole and complicated Urinary Tract Infections (cUTI), including Pyelonephritis. Launch Date 2015
Complicated urinary tract infections 12 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23371303 https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206494s002lbl.pdf	Curative		Approved 8583	AVYCAZ Approved Use AVYCAZ is a combination of ceftazidime, a cephalosporin, and avibactam, a beta-lactamase inhibitor, indicated for the treatment of patients 18 years or older with the following infections caused by designated susceptible microorganisms: complicated Intra-abdominal Infections (cIAI), used in combination with metronidazole and complicated Urinary Tract Infections (cUTI), including Pyelonephritis. Launch Date 2015

C_max

Value	Dose	Co-administered	Analyte	Population
15.2 mg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206494s005,s006lbl.pdf	0.5 g single, intravenous dose: 0.5 g route of administration: Intravenous experiment type: SINGLE co-administered: Ceftazidime	Ceftazidime	[NO STEREO] AVE-1330A FREE ACID\|[NO STEREO] AVIBACTAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
14.6 mg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206494s005,s006lbl.pdf	0.5 g 3 times / day multiple, intravenous dose: 0.5 g route of administration: Intravenous experiment type: MULTIPLE co-administered: CEFTAZIDIME	CEFTAZIDIME	AVIBACTAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
42.1 mg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206494s005,s006lbl.pdf	0.5 g single, intravenous dose: 0.5 g route of administration: Intravenous experiment type: SINGLE co-administered: Ceftazidime	Ceftazidime	[NO STEREO] AVE-1330A FREE ACID\|[NO STEREO] AVIBACTAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
38.2 mg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206494s005,s006lbl.pdf	0.5 g 3 times / day multiple, intravenous dose: 0.5 g route of administration: Intravenous experiment type: MULTIPLE co-administered: CEFTAZIDIME	CEFTAZIDIME	AVIBACTAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.22 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206494s005,s006lbl.pdf	0.5 g single, intravenous dose: 0.5 g route of administration: Intravenous experiment type: SINGLE co-administered: Ceftazidime	Ceftazidime	[NO STEREO] AVE-1330A FREE ACID\|[NO STEREO] AVIBACTAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.71 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206494s005,s006lbl.pdf	0.5 g 3 times / day multiple, intravenous dose: 0.5 g route of administration: Intravenous experiment type: MULTIPLE co-administered: CEFTAZIDIME	CEFTAZIDIME	AVIBACTAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
93% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206494s005,s006lbl.pdf	0.5 g single, intravenous dose: 0.5 g route of administration: Intravenous experiment type: SINGLE co-administered: Ceftazidime	Ceftazidime	[NO STEREO] AVE-1330A FREE ACID\|[NO STEREO] AVIBACTAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1000 mg 3 times / day multiple, intravenous Highest studied dose Dose: 1000 mg, 3 times / day Route: intravenous Route: multiple Dose: 1000 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25813217	healthy, 18–45 years Health Status: healthy Age Group: 18–45 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/25813217	Sources: https://pubmed.ncbi.nlm.nih.gov/25813217
2000 mg single, intravenous Highest studied dose Dose: 2000 mg Route: intravenous Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/25813217	healthy, 18–45 years Health Status: healthy Age Group: 18–45 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/25813217	Sources: https://pubmed.ncbi.nlm.nih.gov/25813217
500 mg single, oral Dose: 500 mg Route: oral Route: single Dose: 500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/25813217	healthy, 28.9 years Health Status: healthy Age Group: 28.9 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/25813217	Sources: https://pubmed.ncbi.nlm.nih.gov/25813217

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087	inhibitor 2438 inducer 440	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BSEP 550 MRP4 290 CYP 110 UGT1A1 246 P-gp 1741 BCRP 910 OAT1 725 OAT3 747 OATP1B1 1079 OATP1B3 961 OCT1 620 OCT2 779 CYP1A2 2153 CYP2A6 879 CYP2B6 926 CYP2C8 1057 CYP2C19 2057 CYP2E1 1060 CYP3A4/5 296	OAT1 395 OAT3 391 P-gp 2052 BCRP 697 MRP4 91 OCT2 434	CYP1A2 832 CYP2B6 669 CYP2E1 131

Drug as perpetrator

Target	Modality	Activity
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
BSEP 554	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP 150	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf#page=38 Page: 38.0	no
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP3A4/5 357	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
MRP4 345	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
UGT1A1 303	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf#page=38 Page: 38.0	no
CYP2E1 1146	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	yes

Drug as victim

Target	Modality	Activity
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf#page=38 Page: 38.0	no
MRP4 91	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf#page=38 Page: 38.0	no
OCT2 434	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf#page=38 Page: 38.0	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf#page=38 Page: 38.0	no
OAT1 395	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf#page=4 Page: 4.0	yes
OAT3 391	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf#page=4 Page: 4.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf#page=18 Page: 18.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:85984	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:85984
ChemicalBook	CB02582836	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB02582836
ZINC	ZINC000009302239	http://zinc15.docking.org/substances/ZINC000009302239

PubMed

Title	Date	PubMed
In vitro activity of AVE1330A, an innovative broad-spectrum non-beta-lactam beta-lactamase inhibitor.	2004 Aug	15254025
Avibactam is a covalent, reversible, non-β-lactam β-lactamase inhibitor.	2012 Jul 17	22753474
Avibactam and class C β-lactamases: mechanism of inhibition, conservation of the binding pocket, and implications for resistance.	2014 Oct	25022578

Patents

Sample Use Guides

In Vivo Use Guide

AVYCAZ 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) for injection administered every 8 hours by intravenous (IV) infusion over 2 hours in patients 18 years of age and older with creatinine clearance (CrCl) greater than 50 mL/min. For treatment of Complicated Intra-abdominal Infections (cIAI), metronidazole should be given concurrently. Recommended duration of treatment: cIAI: 5 to 14 days, Complicated Urinary Tract Infections (cUTI) including pyelonephritis: 7 to 14 days.

Route of Administration: Intravenous

In Vitro Use Guide

MICs of ceftazidime/AVE1330A(avibactam) for Enterobacteriaceae were at least eight-fold lower than those of ceftazidime alone. All of the Escherichia coli, Klebsiella pneumoniae, Citrobacter and Proteus mirabilis strains, including ceftazidime-resistant isolates, were inhibited at 4-8 mg/L. Only 2 mg/L were required to inhibit other Proteeae, Enterobacter, Salmonella and Serratia.

Name

Type

Language

Avycaz component avibactam sodium

Preferred Name

English

Avibactam sodium

Official Name

English

Avibactam sodium [USAN]

Common Name

English

Avibactam sodium salt [MI]

Common Name

English

Avibactam sodium [WHO-DD]

Common Name

English

Sulfuric acid, mono[(1R,2S,5R)-2-(aminocarbonyl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl] ester, sodium salt (1:1)

Systematic Name

English

Avibactam sodium [JAN]

Common Name

English

(2S,5R)-7-Oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide monosodium salt

Systematic Name

English

Avibactam sodium [ORANGE BOOK]

Common Name

English

Sodium (1R,2S,5R)-2-carbamoyl-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate

Systematic Name

English

EMBLAVEO COMPONENT AVIBACTAM SODIUM

Brand Name

English

NXL104

Code

English

NXL-104

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C258