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

Details

Stereochemistry ABSOLUTE
Molecular Formula C8H9NO5
Molecular Weight 199.1611
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of CLAVULANIC ACID

SMILES

C(\[H])(=C/1\[C@]([H])(C(=O)O)N2C(=O)C[C@@]2([H])O1)/CO

InChI

InChIKey=HZZVJAQRINQKSD-PBFISZAISA-N
InChI=1S/C8H9NO5/c10-2-1-4-7(8(12)13)9-5(11)3-6(9)14-4/h1,6-7,10H,2-3H2,(H,12,13)/b4-1-/t6-,7-/m1/s1

HIDE SMILES / InChI
Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is a β-lactam structurally related to the penicillins and possesses the ability to inactivate a wide variety of β-lactamases by blocking the active sites of these enzymes. Clavulanic acid is particularly active against the clinically important plasmid-mediated β-lactamases frequently responsible for transferred drug resistance to penicillins and cephalosporins. Clavulanic acid is used in conjunction with amoxicillin for the treatment of bronchitis and urinary tract, skin, and soft tissue infections caused by beta-lactamase producing organisms. Clavulanic acid competitively and irreversibly inhibits a wide variety of beta-lactamases, commonly found in microorganisms resistant to penicillins and cephalosporins. Binding and irreversibly inhibiting the beta-lactamase results in a restauration of the antimicrobial activity of beta-lactam antibiotics against lactamase-secreting-resistant bacteria. By inactivating beta-lactamase (the bacterial resistance protein), the accompanying penicillin/cephalosporin drugs may be made more potent as well.

CNS Activity

Curator's Comment:: Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier permeability and safety profile. Clavulanic acid has been proposed to have anti-depressant activity and was in Phase IIb clinical trials for the treatment of Major Depressive Disorder (MDD). Studies have also shown that clavulanic acid suppresses anxiety and enhances sexual functions in rodent and primate models by a mechanism involving central nervous system (CNS) modulation.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Augmentin

Approved Use

AUGMENTIN is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the conditions listed below: Lower Respiratory Tract Infections – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis. Otitis Media – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis. Sinusitis – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis. Skin and Skin Structure Infections – caused by β-lactamase–producing strains of S. aureus, E. coli, and Klebsiella spp. Urinary Tract Infections – caused by β-lactamase–producing strains of E. coli, Klebsiella spp. and Enterobacter spp.

Launch Date

8.3211839E11
Curative
Augmentin

Approved Use

AUGMENTIN is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the conditions listed below: Lower Respiratory Tract Infections – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis. Otitis Media – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis. Sinusitis – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis. Skin and Skin Structure Infections – caused by β-lactamase–producing strains of S. aureus, E. coli, and Klebsiella spp. Urinary Tract Infections – caused by β-lactamase–producing strains of E. coli, Klebsiella spp. and Enterobacter spp.

Launch Date

8.3211839E11
Curative
Augmentin

Approved Use

AUGMENTIN is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the conditions listed below: Lower Respiratory Tract Infections – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis. Otitis Media – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis. Sinusitis – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis. Skin and Skin Structure Infections – caused by β-lactamase–producing strains of S. aureus, E. coli, and Klebsiella spp. Urinary Tract Infections – caused by β-lactamase–producing strains of E. coli, Klebsiella spp. and Enterobacter spp.

Launch Date

8.3211839E11
Curative
Augmentin

Approved Use

AUGMENTIN is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the conditions listed below: Lower Respiratory Tract Infections – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis. Otitis Media – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis. Sinusitis – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis. Skin and Skin Structure Infections – caused by β-lactamase–producing strains of S. aureus, E. coli, and Klebsiella spp. Urinary Tract Infections – caused by β-lactamase–producing strains of E. coli, Klebsiella spp. and Enterobacter spp.

Launch Date

8.3211839E11
Curative
Augmentin

Approved Use

AUGMENTIN is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the conditions listed below: Lower Respiratory Tract Infections – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis. Otitis Media – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis. Sinusitis – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis. Skin and Skin Structure Infections – caused by β-lactamase–producing strains of S. aureus, E. coli, and Klebsiella spp. Urinary Tract Infections – caused by β-lactamase–producing strains of E. coli, Klebsiella spp. and Enterobacter spp.

Launch Date

8.3211839E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.63 μg/mL
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered: AMOXICILLIN
CLAVULANIC ACID plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
5.49 μg × h/mL
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered: AMOXICILLIN
CLAVULANIC ACID plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1 h
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered: AMOXICILLIN
CLAVULANIC ACID plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
10 mg/kg 1 times / day steady, oral
Recommended
Dose: 10 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg/kg, 1 times / day
Co-administed with::
amoxicillin(40 to 45 mg/kg)
Sources:
unhealthy, 2 months to 12 years
n = 575
Health Status: unhealthy
Condition: acute otitis media
Age Group: 2 months to 12 years
Sex: unknown
Population Size: 575
Sources:
Other AEs: Diarrhea, Rash urticarial...
125 mg 1 times / day steady, oral
Recommended
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Co-administed with::
amoxicillin(250 to 875 mg)
Sources:
unhealthy, adult
Other AEs: Loose stools, Nausea...
AEs

AEs

AESignificanceDosePopulation
Diaper rash
10 mg/kg 1 times / day steady, oral
Recommended
Dose: 10 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg/kg, 1 times / day
Co-administed with::
amoxicillin(40 to 45 mg/kg)
Sources:
unhealthy, 2 months to 12 years
n = 575
Health Status: unhealthy
Condition: acute otitis media
Age Group: 2 months to 12 years
Sex: unknown
Population Size: 575
Sources:
Diarrhea
10 mg/kg 1 times / day steady, oral
Recommended
Dose: 10 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg/kg, 1 times / day
Co-administed with::
amoxicillin(40 to 45 mg/kg)
Sources:
unhealthy, 2 months to 12 years
n = 575
Health Status: unhealthy
Condition: acute otitis media
Age Group: 2 months to 12 years
Sex: unknown
Population Size: 575
Sources:
Rash urticarial
10 mg/kg 1 times / day steady, oral
Recommended
Dose: 10 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg/kg, 1 times / day
Co-administed with::
amoxicillin(40 to 45 mg/kg)
Sources:
unhealthy, 2 months to 12 years
n = 575
Health Status: unhealthy
Condition: acute otitis media
Age Group: 2 months to 12 years
Sex: unknown
Population Size: 575
Sources:
Vaginitis 1%
125 mg 1 times / day steady, oral
Recommended
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Co-administed with::
amoxicillin(250 to 875 mg)
Sources:
unhealthy, adult
Vomiting 1%
125 mg 1 times / day steady, oral
Recommended
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Co-administed with::
amoxicillin(250 to 875 mg)
Sources:
unhealthy, adult
Nausea 3%
125 mg 1 times / day steady, oral
Recommended
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Co-administed with::
amoxicillin(250 to 875 mg)
Sources:
unhealthy, adult
Rash urticarial 3%
125 mg 1 times / day steady, oral
Recommended
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Co-administed with::
amoxicillin(250 to 875 mg)
Sources:
unhealthy, adult
Loose stools 9%
125 mg 1 times / day steady, oral
Recommended
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Co-administed with::
amoxicillin(250 to 875 mg)
Sources:
unhealthy, adult
PubMed

PubMed

TitleDatePubMed
In vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium fortuitum and Mycobacterium chelonei to augmentin.
1986 Aug
In vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis, Mycobacterium avium, Mycobacterium fortuitum, and Mycobacterium chelonae to ticarcillin in combination with clavulanic acid.
1987 Jan
Immunogenicity and allergenicity studies on two beta-lactam structures, a clavam, clavulanic acid, and a carbapenem: structure-activity relationships.
1988
In vitro activity of antimicrobial agents against mycobacteria.
1988
Cholestatic hepatitis due to antibacterial combination of amoxicillin and clavulanic acid (augmentin)
1989 Oct
beta-Lactamase inhibitors and the inducibility of the beta-lactamase of Mycobacterium tuberculosis.
1992 Mar
beta-Lactamase activity in mycobacteria including Mycobacterium avium and suppression of their growth by a beta-lactamase-stable antibiotic.
1995
Can penicillins and other beta-lactam antibiotics be used to treat tuberculosis?
1995 Dec
beta-Lactam drug allergens: fine structural recognition patterns of cephalosporin-reactive IgE antibodies.
1996 Jul-Aug
Suppression of the growth of six potentially-pathogenic mycobacteria by beta-lactam/beta-lactamase-inhibitors.
1997
Hypersensitivity to clavulanic acid in children.
2008 Sep-Oct
A correlation between the in vitro drug toxicity of drugs to cell lines that express human P450s and their propensity to cause liver injury in humans.
2014 Jan
Patents

Sample Use Guides

Adults The usual adult dose is one 500 mg/125 mg Amoxicillin and Clavulanate Potassium Tablet every 12 hours or one 250 mg/125 mg Amoxicillin and Clavulanate Potassium Tablet every 8 hours. For more severe infections and infections of the respiratory tract, the dose should be one 875 mg/125 mg Amoxicillin and Clavulanate Potassium Tablet every 12 hours or one 500 mg/125 mg Amoxicillin and Clavulanate Potassium Tablet every 8 hours. Adults who have difficulty swallowing may be given the 125 mg/31.25 mg per 5 mL or 250 mg/62.5 mg per 5 mL suspension in place of the 500 mg/125 mg tablet. The 200 mg/28.5 mg per 5 mL suspension or the 400 mg/57 mg per 5 mL suspension may be used in place of the 875 mg/125 mg tablet.
Route of Administration: Oral
The purified beta-lactamase enzyme focused at pI 5.4 and was strongly inhibited in vitro by clavulanic acid (IC50 = 0.09 uM).
Name Type Language
CLAVULANIC ACID
INN   MART.   MI   WHO-DD  
INN  
Official Name English
CLAVULANIC ACID [WHO-DD]
Common Name English
CLAVULANATE [VANDF]
Common Name English
BRL 14151
Code English
CLAVULANIC ACID [INN]
Common Name English
(2R,3Z,5R)-3-(2-HYDROXYETHYLIDENE)-7-OXO-4-OXA-1-AZABICYCLO(3.2.0)HEPTANE-2-CARBOXYLIC ACID
Systematic Name English
BRL-14151
Code English
CLAVULANIC ACID [MART.]
Common Name English
CLAVULANATE
VANDF  
Common Name English
SERDAXIN
Brand Name English
4-OXA-1-AZABICYCLO(3.2.0)HEPTANE-2-CARBOXYLIC ACID, 3-(2-HYDROXYETHYLIDENE)-7-OXO-, (2R-(2.ALPHA.,3Z,5.ALPHA.))-
Common Name English
(Z)-(2R,5R)-3-(2-HYDROXYETHYLIDENE)-7-OXO-4-OXA-1-AZABICYCLO(3.2.0)HEPTANE-2-CARBOXYLIC ACID
Systematic Name English
RX-10100
Code English
CLAVULANIC ACID [MI]
Common Name English
Classification Tree Code System Code
NDF-RT N0000000202
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
LIVERTOX 215
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 6.2.1 (AMO/CLA)
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
NCI_THESAURUS C260
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
WHO-ATC J01DH51
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
NDF-RT N0000175930
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
Code System Code Type Description
EPA CompTox
58001-44-8
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY
RXCUI
48203
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
ALTERNATIVE
MERCK INDEX
M3609
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY Merck Index
DRUG BANK
DB00766
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY
WIKIPEDIA
CLAVULANIC ACID
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY
ChEMBL
CHEMBL777
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY
LACTMED
Ticarcillin and Clavulanic Acid
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY
CAS
58001-44-8
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY
ECHA (EC/EINECS)
261-069-2
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY
INN
4948
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY
PUBCHEM
5280980
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY
EVMPD
SUB06642MIG
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY
MESH
D019818
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY
FDA UNII
23521W1S24
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY
RXCUI
21216
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY
DRUG CENTRAL
669
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY
NCI_THESAURUS
C61681
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY
LACTMED
Amoxicillin and Clavulanic Acid
Created by admin on Sat Jun 26 11:25:15 UTC 2021 , Edited by admin on Sat Jun 26 11:25:15 UTC 2021
PRIMARY