U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C27H31FN4O8.2ClH
Molecular Weight 631.477
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ERAVACYCLINE DIHYDROCHLORIDE

SMILES

Cl.Cl.[H][C@@]12CC3=C(F)C=C(NC(=O)CN4CCCC4)C(O)=C3C(=O)C1=C(O)[C@]5(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@]5([H])C2

InChI

InChIKey=JYCNMRVZELJVAW-RZVFYPHASA-N
InChI=1S/C27H31FN4O8.2ClH/c1-31(2)20-13-8-11-7-12-14(28)9-15(30-16(33)10-32-5-3-4-6-32)21(34)18(12)22(35)17(11)24(37)27(13,40)25(38)19(23(20)36)26(29)39;;/h9,11,13,20,34,36-37,40H,3-8,10H2,1-2H3,(H2,29,39)(H,30,33);2*1H/t11-,13-,20-,27-;;/m0../s1

HIDE SMILES / InChI

Molecular Formula C27H31FN4O8
Molecular Weight 558.5554
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Eravacycline, known as Xerava by Tetraphase Pharmaceuticals, is a fully synthetic fluorocycline antibiotic of the tetracycline class with activity against clinically significant gram-negative, gram-positive aerobic, and facultative bacteria. This includes most of those bacteria resistant to cephalosporins, fluoroquinolones, β-lactam/β-lactamase inhibitors, multidrug-resistant strains, and carbapenem-resistant Enterobacteriaceae, and the majority of anaerobic pathogens. It was first approved by the FDA on August 27, 2018. Eravacycline disrupts bacterial protein synthesis by binding to the 30S ribosomal subunit thus preventing the incorporation of amino acid residues into elongating peptide chains.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P0A7V8
Gene ID: 947793.0
Gene Symbol: rpsD
Target Organism: Escherichia coli (strain K12)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
XERAVA

Approved Use

XERAVA is a tetracycline class antibacterial indicated for the treatment of complicated intra-abdominal infections in patients 18 years of age and older. (1.1) Limitations of Use XERAVA is not indicated for the treatment of complicated urinary tract infections (cUTI). (1.1) To reduce the development of drug -resistant bacteria and maintain the effectiveness of XERAVA and other antibacterial drugs, XERAVA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. (1.2)

Launch Date

2018
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2125 ng/mL
1 mg/kg single, intravenous
dose: 1 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
ERAVACYCLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1825 ng/mL
1 mg/kg 2 times / day steady-state, intravenous
dose: 1 mg/kg
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
ERAVACYCLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4305 ng × h/mL
1 mg/kg single, intravenous
dose: 1 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
ERAVACYCLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
6309 ng × h/mL
1 mg/kg 2 times / day steady-state, intravenous
dose: 1 mg/kg
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
ERAVACYCLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
20 h
1 mg/kg single, intravenous
dose: 1 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
ERAVACYCLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
20 h
1 mg/kg 2 times / day steady-state, intravenous
dose: 1 mg/kg
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
ERAVACYCLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
15.5%
1 mg/kg single, intravenous
dose: 1 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
ERAVACYCLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
15.5%
1 mg/kg 2 times / day steady-state, intravenous
dose: 1 mg/kg
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
ERAVACYCLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
3 mg/kg 1 times / day single, intravenous
Highest studied dose
Dose: 3 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 3 mg/kg, 1 times / day
Sources:
healthy, 18–48 years
n = 42
Other AEs: Nausea, Vomiting...
1.5 mg/kg 1 times / day single, intravenous
MTD
Dose: 1.5 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 1.5 mg/kg, 1 times / day
Sources:
healthy, 18–48 years
n = 42
1 mg/kg 1 times / day single, intravenous
Recommended
Dose: 1 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 1 mg/kg, 1 times / day
Sources:
healthy, 18–48 years
n = 42
Disc. AE: Pyrexia...
0.25 mg/kg 1 times / day single, intravenous
Dose: 0.25 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 0.25 mg/kg, 1 times / day
Sources:
healthy, 18–48 years
n = 42
Disc. AE: Pyrexia...
1.5 mg/kg 1 times / day single, intravenous (min)
Dose: 1.5 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 1.5 mg/kg, 1 times / day
Sources:
healthy, 18–48 years
n = 42
Health Status: healthy
Age Group: 18–48 years
Sex: M+F
Population Size: 42
Sources:
DLT: Nausea, Vomiting...
Dose limiting toxicities:
Nausea
Vomiting
Sources:
1 mg/kg 2 times / day multiple, intravenous
MTD|Highest studied dose
Dose: 1 mg/kg, 2 times / day
Route: intravenous
Route: multiple
Dose: 1 mg/kg, 2 times / day
Sources:
healthy, 19–50 years
n = 24
Disc. AE: Phlebitis superficial...
1 mg/kg 2 times / day multiple, intravenous
Recommended
Dose: 1 mg/kg, 2 times / day
Route: intravenous
Route: multiple
Dose: 1 mg/kg, 2 times / day
Sources:
healthy, 19–50 years
n = 24
Disc. AE: Decreased appetite, Nausea...
AEs leading to
discontinuation/dose reduction:
Decreased appetite (4.2%)
Nausea (4.2%)
Vomiting (4.2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Vomiting grade 1-2, <10%
3 mg/kg 1 times / day single, intravenous
Highest studied dose
Dose: 3 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 3 mg/kg, 1 times / day
Sources:
healthy, 18–48 years
n = 42
Nausea grade 1-2, >10
3 mg/kg 1 times / day single, intravenous
Highest studied dose
Dose: 3 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 3 mg/kg, 1 times / day
Sources:
healthy, 18–48 years
n = 42
Pyrexia 2.4%
Disc. AE
1 mg/kg 1 times / day single, intravenous
Recommended
Dose: 1 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 1 mg/kg, 1 times / day
Sources:
healthy, 18–48 years
n = 42
Pyrexia 2.4%
Disc. AE
0.25 mg/kg 1 times / day single, intravenous
Dose: 0.25 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 0.25 mg/kg, 1 times / day
Sources:
healthy, 18–48 years
n = 42
Nausea DLT
1.5 mg/kg 1 times / day single, intravenous (min)
Dose: 1.5 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 1.5 mg/kg, 1 times / day
Sources:
healthy, 18–48 years
n = 42
Health Status: healthy
Age Group: 18–48 years
Sex: M+F
Population Size: 42
Sources:
Vomiting DLT
1.5 mg/kg 1 times / day single, intravenous (min)
Dose: 1.5 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 1.5 mg/kg, 1 times / day
Sources:
healthy, 18–48 years
n = 42
Health Status: healthy
Age Group: 18–48 years
Sex: M+F
Population Size: 42
Sources:
Phlebitis superficial 4.2%
Disc. AE
1 mg/kg 2 times / day multiple, intravenous
MTD|Highest studied dose
Dose: 1 mg/kg, 2 times / day
Route: intravenous
Route: multiple
Dose: 1 mg/kg, 2 times / day
Sources:
healthy, 19–50 years
n = 24
Decreased appetite 4.2%
Disc. AE
1 mg/kg 2 times / day multiple, intravenous
Recommended
Dose: 1 mg/kg, 2 times / day
Route: intravenous
Route: multiple
Dose: 1 mg/kg, 2 times / day
Sources:
healthy, 19–50 years
n = 24
Nausea 4.2%
Disc. AE
1 mg/kg 2 times / day multiple, intravenous
Recommended
Dose: 1 mg/kg, 2 times / day
Route: intravenous
Route: multiple
Dose: 1 mg/kg, 2 times / day
Sources:
healthy, 19–50 years
n = 24
Vomiting 4.2%
Disc. AE
1 mg/kg 2 times / day multiple, intravenous
Recommended
Dose: 1 mg/kg, 2 times / day
Route: intravenous
Route: multiple
Dose: 1 mg/kg, 2 times / day
Sources:
healthy, 19–50 years
n = 24
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
weak [Inhibition 85.6 uM]
yes [Inhibition 36 uM]
yes [Inhibition 36 uM]
yes [Inhibition 36 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
yes
yes
yes (co-administration study)
Comment: Concomitant use of itraconazole (strong CYP3A inhibitor) increased eravacycline Cmax by 5% and AUC by 32%, and decreased eravacycline clearance by 32%
Page: 13.0
yes
yes (co-administration study)
Comment: Concomitant use of rifampin (strong CYP3A4/3A5 inducer) decreased eravacycline AUC by 35% and increased eravacycline clearance by 54%
Page: 13.0
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Fluorocyclines. 1. 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline: a potent, broad spectrum antibacterial agent.
2012 Jan 26
Patents

Sample Use Guides

Administer XERAVA for injection 1 mg/kg by intravenous infusion over approximately 60 minutes every 12 hours for a total duration of 4 to 14 days. (2.1) • Severe Hepatic Impairment (Child Pugh C): 1 mg/kg XERAVA every 12 hours on Day 1, then 1 mg/kg every 24 hours starting on Day 2 for a total duration of 4 to 14 days. (2.2) • Concomitant Use of a Strong Cytochrome P450 Isoenzymes (CYP)3A Inducer: 1.5 mg/kg XERAVA every 12 hours for a total duration of 4 to 14 days. (2.3) For injection: 50 mg of eravacycline (equivalent to 63.5 mg eravacy cline dihydrochloride) as a lyophilized powder in a single-dose vial for reconstitution and further dilution.
Route of Administration: Intravenous
In vitro activity data from Tetraphase Pharmaceuticals studies on the following groups of combined bacterial species: Enterobacteriaceae, 5975 isolates, MIC90 0.5 mcg/mL, ECOV 1 ug/mL All Enterococcus spp., 1403 isolates, MIC90 0.06 ug/mL, ECOV 0.25 ug/mL All Viridans Group Streptococcus, 414 isolates, MIC90 0.06 ug/mL, ECOV 0.12 ug/mL Anaerobes, 1190 isolates, MIC90 1 ug/mL, ECOV 1 ug/mL
Substance Class Chemical
Created
by admin
on Sat Dec 16 03:00:04 GMT 2023
Edited
by admin
on Sat Dec 16 03:00:04 GMT 2023
Record UNII
WK1NMH89VJ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ERAVACYCLINE DIHYDROCHLORIDE
USAN   WHO-DD  
USAN  
Official Name English
Eravacycline dihydrochloride [WHO-DD]
Common Name English
TP-434-046
Code English
(4S,4aS,5aR,12aS)-4-(Dimethylamino)-7-fluoro-3,10,12,12a-tetrahydroxy-1,11-dioxo-9-[(pyrrolidin-1-ylacetyl)amino]-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide dihydrochloride
Common Name English
ERAVACYCLINE DIHYDROCHLORIDE [ORANGE BOOK]
Common Name English
XERAVA
Brand Name English
TP434046
Code English
ERAVACYCLINE DIHYDROCHLORIDE [MI]
Common Name English
1-PYRROLIDINEACETAMIDE, N-((5AR,6AS,7S,10AS)-9-(AMINOCARBONYL)-7-(DIMETHYLAMINO)-4-FLUORO-5,5A,6,6A,7,10,10A,12-OCTAHYDRO-1,8,10A,11-TETRAHYDROXY-10,12-DIOXO-2-NAPHTHACENYL)-, HYDROCHLORIDE (1:2)
Common Name English
ERAVACYCLINE DIHYDROCHLORIDE [USAN]
Common Name English
Code System Code Type Description
ChEMBL
CHEMBL1951095
Created by admin on Sat Dec 16 03:00:04 GMT 2023 , Edited by admin on Sat Dec 16 03:00:04 GMT 2023
PRIMARY
DRUG BANK
DBSALT002787
Created by admin on Sat Dec 16 03:00:04 GMT 2023 , Edited by admin on Sat Dec 16 03:00:04 GMT 2023
PRIMARY
NCI_THESAURUS
C169957
Created by admin on Sat Dec 16 03:00:04 GMT 2023 , Edited by admin on Sat Dec 16 03:00:04 GMT 2023
PRIMARY
FDA UNII
WK1NMH89VJ
Created by admin on Sat Dec 16 03:00:04 GMT 2023 , Edited by admin on Sat Dec 16 03:00:04 GMT 2023
PRIMARY
DRUG CENTRAL
5294
Created by admin on Sat Dec 16 03:00:04 GMT 2023 , Edited by admin on Sat Dec 16 03:00:04 GMT 2023
PRIMARY
CAS
1334714-66-7
Created by admin on Sat Dec 16 03:00:04 GMT 2023 , Edited by admin on Sat Dec 16 03:00:04 GMT 2023
PRIMARY
DAILYMED
WK1NMH89VJ
Created by admin on Sat Dec 16 03:00:04 GMT 2023 , Edited by admin on Sat Dec 16 03:00:04 GMT 2023
PRIMARY
SMS_ID
300000044470
Created by admin on Sat Dec 16 03:00:04 GMT 2023 , Edited by admin on Sat Dec 16 03:00:04 GMT 2023
PRIMARY
RXCUI
2055907
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PRIMARY
EPA CompTox
DTXSID601027691
Created by admin on Sat Dec 16 03:00:04 GMT 2023 , Edited by admin on Sat Dec 16 03:00:04 GMT 2023
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PUBCHEM
56951485
Created by admin on Sat Dec 16 03:00:04 GMT 2023 , Edited by admin on Sat Dec 16 03:00:04 GMT 2023
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MERCK INDEX
m12118
Created by admin on Sat Dec 16 03:00:04 GMT 2023 , Edited by admin on Sat Dec 16 03:00:04 GMT 2023
PRIMARY
USAN
ZZ-70
Created by admin on Sat Dec 16 03:00:04 GMT 2023 , Edited by admin on Sat Dec 16 03:00:04 GMT 2023
PRIMARY
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