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Details

Stereochemistry ABSOLUTE
Molecular Formula C27H31FN4O8
Molecular Weight 558.5565
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ERAVACYCLINE

SMILES

CN(C)[C@@]1([H])[C@]2([H])C[C@]3([H])Cc4c(cc(c(c4C(=O)C3=C([C@@]2(C(=O)C(=C1O)C(=N)O)O)O)O)N=C(CN5CCCC5)O)F

InChI

InChIKey=HLFSMUUOKPBTSM-ISIOAQNYSA-N
InChI=1S/C27H31FN4O8/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)/t11-,13-,20-,27-/m0/s1

HIDE SMILES / InChI
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

1.53532799E12
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
Name Type Language
ERAVACYCLINE
INN   USAN   WHO-DD  
INN   USAN  
Official 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)-
Systematic Name English
ERAVACYCLINE [USAN]
Common Name English
TP-434
Code English
ERAVACYCLINE [INN]
Common Name English
ERAVACYCLINE [MI]
Common Name 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
Systematic Name English
ERAVACYCLINE [WHO-DD]
Common Name English
(4S,4AS,5AR,12AS)-4-(DIMETHYLAMINO)-7-FLUORO-3,10,12,12ATETRAHYDROXY-1,11-DIOXO-9-(2-(PYRROLIDIN-1-YL)ACETAMIDO)-1,4,4A,5,5A,6,11,12A-OCTAHYDROTETRACENE-2-CARBOXAMIDE
Systematic Name English
Classification Tree Code System Code
WHO-ATC J01AA13
Created by admin on Sat Jun 26 11:51:58 UTC 2021 , Edited by admin on Sat Jun 26 11:51:58 UTC 2021
Code System Code Type Description
DRUG BANK
DB12329
Created by admin on Sat Jun 26 11:51:58 UTC 2021 , Edited by admin on Sat Jun 26 11:51:58 UTC 2021
PRIMARY
ChEMBL
CHEMBL1951095
Created by admin on Sat Jun 26 11:51:58 UTC 2021 , Edited by admin on Sat Jun 26 11:51:58 UTC 2021
PRIMARY
LACTMED
Eravacycline
Created by admin on Sat Jun 26 11:51:58 UTC 2021 , Edited by admin on Sat Jun 26 11:51:58 UTC 2021
PRIMARY
RXCUI
2055906
Created by admin on Sat Jun 26 11:51:58 UTC 2021 , Edited by admin on Sat Jun 26 11:51:58 UTC 2021
PRIMARY
CAS
1207283-85-9
Created by admin on Sat Jun 26 11:51:58 UTC 2021 , Edited by admin on Sat Jun 26 11:51:58 UTC 2021
PRIMARY
MERCK INDEX
M12118
Created by admin on Sat Jun 26 11:51:58 UTC 2021 , Edited by admin on Sat Jun 26 11:51:58 UTC 2021
PRIMARY
NCI_THESAURUS
C171907
Created by admin on Sat Jun 26 11:51:58 UTC 2021 , Edited by admin on Sat Jun 26 11:51:58 UTC 2021
PRIMARY
INN
9702
Created by admin on Sat Jun 26 11:51:58 UTC 2021 , Edited by admin on Sat Jun 26 11:51:58 UTC 2021
PRIMARY
FDA UNII
07896928ZC
Created by admin on Sat Jun 26 11:51:58 UTC 2021 , Edited by admin on Sat Jun 26 11:51:58 UTC 2021
PRIMARY