clavulanic acid ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
beta-lactamase inhibitors 669 58001-44-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • clavulanic acid
  • clavulanate
  • clavulanate potassium
  • clavulante potasium
  • clavulanate potassium salt
A beta-lactam antibiotic produced by the actinobacterium Streptomyces clavuligerus. It is a suicide inhibitor of bacterial beta-lactamase enzymes. Administered alone, it has only weak antibacterial activity against most organisms, but given in combination with other beta-lactam antibiotics it prevents antibiotic inactivation by microbial lactamase.
  • Molecular weight: 199.16
  • Formula: C8H9NO5
  • CLOGP: -1.06
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 2
  • TPSA: 87.07
  • ALOGS: 0.23
  • ROTB: 2

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 43 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 31.38 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 75 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.22 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 3.10 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.91 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 0.90 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Aug. 6, 1984 FDA DR REDDYS LABS INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Bronchiectasis 116.97 20.07 41 4354 10242 50590487
Bone erosion 111.84 20.07 41 4354 11646 50589083
Acute generalised exanthematous pustulosis 76.86 20.07 29 4366 8909 50591820
Hypothyroidism 75.16 20.07 43 4352 34082 50566647
Neutropenia 56.82 20.07 67 4328 147898 50452831
Anaphylactic reaction 54.89 20.07 42 4353 54013 50546716
Drug hypersensitivity 54.30 20.07 86 4309 250924 50349805
Nail dystrophy 44.65 20.07 11 4384 800 50599929
Loss of personal independence in daily activities 43.45 20.07 41 4354 70009 50530720
Hepatitis cholestatic 39.04 20.07 16 4379 6101 50594628
Cholecystitis chronic 38.04 20.07 18 4377 9651 50591078
Axillary pain 37.35 20.07 11 4384 1573 50599156
Jaundice 32.35 20.07 23 4372 26406 50574323
Pruritus 32.32 20.07 74 4321 283494 50317235
Catheter site haemorrhage 31.15 20.07 11 4384 2799 50597930
Toxic skin eruption 29.73 20.07 16 4379 11235 50589494
Red blood cell sedimentation rate abnormal 29.17 20.07 18 4377 16325 50584404
Hyperleukocytosis 29.15 20.07 7 4388 457 50600272
Cholestasis 28.57 20.07 21 4374 25380 50575349
Appendicitis 25.04 20.07 12 4383 6612 50594117
Synovitis 22.08 20.07 39 4356 123826 50476903
Thrombotic microangiopathy 21.84 20.07 12 4383 8779 50591950
Joint stiffness 21.22 20.07 19 4376 30289 50570440
Hyperchlorhydria 20.90 20.07 7 4388 1521 50599208
Meningitis aseptic 20.32 20.07 9 4386 4143 50596586

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hepatocellular injury 89.68 26.57 43 2848 21200 29550436
Cholestasis 57.45 26.57 33 2858 23429 29548207
Urethral valves 54.89 26.57 11 2880 272 29571364
Spinal muscular atrophy 42.98 26.57 9 2882 278 29571358
Pneumococcal sepsis 42.64 26.57 11 2880 855 29570781
Anaphylactic shock 41.55 26.57 22 2869 13314 29558322
Anaphylactic reaction 40.35 26.57 28 2863 27545 29544091
Stevens-Johnson syndrome 37.18 26.57 22 2869 16475 29555161
Meningitis aseptic 35.59 26.57 12 2879 2364 29569272
Kounis syndrome 34.51 26.57 11 2880 1818 29569818
Ischaemic cerebral infarction 31.77 26.57 9 2882 996 29570640
Motor neurone disease 30.04 26.57 7 2884 356 29571280
Increased bronchial secretion 27.75 26.57 9 2882 1572 29570064

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Anaphylactic reaction 92.31 18.52 66 6191 68598 64423877
Hepatocellular injury 88.66 18.52 55 6202 45180 64447295
Cholestasis 84.01 18.52 53 6204 44819 64447656
Acute generalised exanthematous pustulosis 73.59 18.52 33 6224 14025 64478450
Bone erosion 56.83 18.52 26 6231 11569 64480906
Meningitis aseptic 55.86 18.52 21 6236 5709 64486766
Bronchiectasis 51.91 18.52 26 6231 14114 64478361
Kounis syndrome 48.29 18.52 16 6241 3009 64489466
Anaphylactic shock 45.01 18.52 31 6226 30297 64462178
Jaundice 44.09 18.52 37 6220 48475 64444000
Stevens-Johnson syndrome 43.87 18.52 32 6225 34217 64458258
Nail dystrophy 43.41 18.52 11 6246 802 64491673
Spinal muscular atrophy 42.82 18.52 9 6248 285 64492190
Hepatitis cholestatic 40.69 18.52 21 6236 12134 64480341
Drug hypersensitivity 39.11 18.52 77 6180 237738 64254737
Pneumococcal sepsis 38.26 18.52 11 6246 1293 64491182
Pruritus 36.38 18.52 88 6169 312312 64180163
Axillary pain 35.18 18.52 11 6246 1721 64490754
Toxic epidermal necrolysis 33.05 18.52 28 6229 37138 64455337
Hypothyroidism 32.98 18.52 29 6228 40428 64452047
Liver injury 29.63 18.52 24 6233 29908 64462567
Jaundice cholestatic 29.07 18.52 15 6242 8655 64483820
Motor neurone disease 28.76 18.52 7 6250 432 64492043
Neutropenia 27.32 18.52 67 6190 239557 64252918
Clostridium difficile colitis 25.21 18.52 21 6236 27202 64465273
Aspartate aminotransferase increased 24.96 18.52 43 6214 119745 64372730
Bronchospasm 24.94 18.52 19 6238 21663 64470812
Catheter site haemorrhage 24.73 18.52 11 6246 4580 64487895
Stoma closure 24.67 18.52 5 6252 132 64492343
Respiratory tract infection bacterial 24.40 18.52 7 6250 816 64491659
Purpura 24.11 18.52 17 6240 17229 64475246
Increased bronchial secretion 22.65 18.52 9 6248 2833 64489642
Drug reaction with eosinophilia and systemic symptoms 22.46 18.52 27 6230 54190 64438285
Resuscitation 21.76 18.52 8 6249 2043 64490432
Ischaemic cerebral infarction 21.68 18.52 8 6249 2064 64490411
Bronchial disorder 21.52 18.52 8 6249 2107 64490368
Joint stiffness 21.26 18.52 20 6237 30384 64462091
Lower respiratory tract infection bacterial 21.18 18.52 6 6251 668 64491807
Rash 21.01 18.52 94 6163 458455 64034020
Cholangitis 20.80 18.52 13 6244 10789 64481686
Hepatitis acute 20.60 18.52 14 6243 13375 64479100
Sputum increased 20.52 18.52 9 6248 3626 64488849
Alanine aminotransferase increased 20.41 18.52 43 6214 138988 64353487
Toxic skin eruption 20.23 18.52 16 6241 19268 64473207
Cholecystitis chronic 19.98 18.52 12 6245 9275 64483200
Circulatory collapse 19.50 18.52 20 6237 33712 64458763
Brain injury 19.20 18.52 12 6245 9953 64482522
Disease complication 19.16 18.52 9 6248 4246 64488229
Hyperbilirubinaemia 18.89 18.52 16 6241 21189 64471286

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
FDA MoA N0000000202 beta Lactamase Inhibitors
FDA EPC N0000175930 beta Lactamase Inhibitor
CHEBI has role CHEBI:35474 anti-anxiety agents
CHEBI has role CHEBI:35625 beta-lactamase inhibitors
CHEBI has role CHEBI:36047 antibacterial drugs
CHEBI has role CHEBI:33281 antibiotics
MeSH PA D000900 Anti-Bacterial Agents
MeSH PA D000890 Anti-Infective Agents
MeSH PA D065093 beta-Lactamase Inhibitors
MeSH PA D004791 Enzyme Inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Septicemia due to Escherichia coli indication 9323009
Bacterial septicemia indication 10001005 DOID:0040085
Infection of skin AND/OR subcutaneous tissue indication 19824006
Staphylococcal pneumonia indication 22754005
Bacterial pneumonia indication 53084003 DOID:874
Klebsiella cystitis indication 60867007
Pneumonia due to Klebsiella pneumoniae indication 64479007
Urinary tract infectious disease indication 68566005
Haemophilus influenzae pneumonia indication 70036007
Infection due to Escherichia coli indication 71057007
Rhinoscleroma indication 72409005 DOID:11336
Acute bacterial sinusitis indication 75498004
Bacterial infection due to Klebsiella pneumoniae indication 186435004
Pneumococcal pneumonia indication 233607000
Escherichia coli urinary tract infection indication 301011002
Bacterial urinary infection indication 312124009
Infective otitis media indication 312218008
Infection due to Staphylococcus aureus indication 406602003
Osteomyelitis due to Staphylococcus aureus indication 428783003
Pneumonia due to Staphylococcus aureus indication 441658007
Sepsis due to Staphylococcus aureus indication 448417001
Sepsis due to Pseudomonas indication 448813005
Bacteroides Endometritis indication
Pneumococcal Acute Otitis Media indication
Haemophilus Parainfluenzae Pneumonia indication
Pseudomonas Aeruginosa Urinary Tract Infection indication
Klebsiella Endometritis indication
Klebsiella Pneumoniae Peritonitis indication
Haemophilus Influenzae Acute Otitis Media indication
Moraxella Catarrhalis Pneumonia indication
Moraxella Catarrhalis Acute Otitis Media indication
Staphylococcus Aureus Joint Infection indication
Staphylococcus Aureus Urinary Tract Infection indication
E. Coli Peritonitis indication
Enterobacter Endometritis indication
Bacteroides Peritonitis indication
Serratia Urinary Tract Infection indication
Citrobacter Urinary Tract Infection indication
Staphylococcus Endometritis indication
E. Coli Endometritis indication
Acute otitis media off-label use 3110003
Pyrexia of unknown origin off-label use 7520000
Chronic purulent otitis media off-label use 38394007 DOID:14247
Cholangitis off-label use 82403002 DOID:9446
Human bite - wound off-label use 262555007
Chancroid off-label use 266143009 DOID:13778
Diverticulitis of gastrointestinal tract off-label use 271366000
Dog bite - wound off-label use 283734005
Cat bite - wound off-label use 283782004
Acute exacerbation of chronic bronchitis off-label use 425748003
Pseudomonas Respiratory Tract Infection in Cystic Fibrosis off-label use
Diabetic Foot Infection off-label use
Obstruction of bile duct contraindication 30144000
Kidney disease contraindication 90708001 DOID:557
Disease of liver contraindication 235856003 DOID:409
Infectious mononucleosis contraindication 271558008 DOID:8568
Pseudomembranous enterocolitis contraindication 397683000




๐Ÿถ Veterinary Drug Use

SpeciesUseRelation
Dogs Urinary tract infections caused by Escherichia coli Indication
Dogs Skin and soft tissue infections caused by beta-lactamase producing Staphylococcus aureus Indication
Dogs Skin and soft tissue infections caused by Staphylococcus spp Indication
Dogs Skin and soft tissue infections caused by Streptococcus spp Indication
Dogs Skin and soft tissue infections caused by Escherichia coli Indication
Dogs Skin and soft tissue infections caused by Pasteurella spp Indication
Cats Urinary tract infections caused by Escherichia coli Indication
Cats Skin and soft tissue infections caused by beta-lactamase producing Staphylococcus aureus Indication
Cats Skin and soft tissue infections caused by Staphylococcus spp Indication
Cats Skin and soft tissue infections caused by Streptococcus spp Indication
Cats Skin and soft tissue infections caused by Escherichia coli Indication
Cats Skin and soft tissue infections caused by Pasteurella spp Indication
Cats Periodontal infections due aerobic and anaerobic bacteria Indication

๐Ÿถ Veterinary products

ProductApplicantIngredients
CLAVAMOX CHEWABLE Tablets, CLAVAMOX tablets Zoetis Inc. 2
Clavamox Drops Zoetis Inc. 2
Clavacillin Dechra Veterinary Products LLC 2
Amoxicillin and Clavulanate Potassium for Oral Suspension Dechra Veterinary Products LLC 2
Amoxicillin and Clavulanate Potassium Tablets Cronus Pharma Specialities India Private Limited 2
Amoxicillin and Clavulanate Potassium for Oral Suspension Cronus Pharma Specialities India Private Limited 2

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.07 acidic
pKa2 13.53 acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Beta-lactamase TEM Enzyme INHIBITOR IC50 10.19 WOMBAT-PK CHEMBL
Beta-lactamase Enzyme IC50 7.82 CHEMBL
Beta-lactamase Enzyme IC50 4 CHEMBL
Beta-lactamase SHV-1 Enzyme IC50 7.55 CHEMBL
Beta-lactamase Enzyme Kd 6.40 CHEMBL
Beta-lactamase OXA-1 Enzyme IC50 5.49 CHEMBL
Beta-lactamase Enzyme IC50 6.10 CHEMBL
Beta-lactamase Enzyme IC50 8.05 CHEMBL
Beta-lactamase Enzyme IC50 7.15 CHEMBL
Beta-lactamase Enzyme IC50 7.07 CHEMBL
Carbapenem-hydrolizing beta-lactamase SFC-1 Enzyme IC50 4.14 CHEMBL
Carbepenem-hydrolyzing beta-lactamase KPC Enzyme Ki 4.96 CHEMBL
Beta-lactamase Enzyme IC50 7.17 CHEMBL
Beta-lactamase Enzyme IC50 8.05 CHEMBL
Beta-lactamase SHV-1 Enzyme IC50 6.77 CHEMBL
Beta-lactamase Enzyme IC50 5.07 CHEMBL
Beta-lactamase GES-13 Enzyme IC50 7 CHEMBL
Beta-lactamase Enzyme IC50 5.76 CHEMBL
Beta-lactamase Enzyme IC50 7.70 CHEMBL
Class D beta-lactamase Unclassified IC50 5.70 CHEMBL
Beta-lactamase Enzyme IC50 8 CHEMBL
Beta-lactamase SHV-5 Enzyme Ki 4.60 CHEMBL
Beta-lactamase Enzyme IC50 7 CHEMBL
Beta-lactamase Enzyme IC50 7 CHEMBL
Beta-lactamase Enzyme MPC 8.72 WOMBAT-PK
Beta-lactamase Enzyme IC50 7.44 CHEMBL

External reference:

IDSource
N0000005804 NUI
D02370 KEGG_DRUG
61177-45-5 SECONDARY_CAS_RN
21216 RXNORM
4018406 VANDF
4019680 VANDF
C0055860 UMLSCUI
CHEBI:48947 CHEBI
J01 PDB_CHEM_ID
CHEMBL777 ChEMBL_ID
DB00766 DRUGBANK_ID
CHEMBL1003 ChEMBL_ID
D019818 MESH_DESCRIPTOR_UI
5280980 PUBCHEM_CID
4948 INN_ID
11128 IUPHAR_LIGAND_ID
23521W1S24 UNII
4463 MMSL
d04405 MMSL
002808 NDDF
002809 NDDF
395938000 SNOMEDCT_US
395939008 SNOMEDCT_US
412318009 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0093-2270 TABLET, CHEWABLE 28.50 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0093-2270 TABLET, CHEWABLE 28.50 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0093-2272 TABLET, CHEWABLE 57 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0093-2272 TABLET, CHEWABLE 57 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0093-2274 TABLET, FILM COATED 125 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0093-2274 TABLET, FILM COATED 125 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0093-2275 TABLET, FILM COATED 125 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0093-2275 TABLET, FILM COATED 125 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0093-2277 POWDER, FOR SUSPENSION 28.50 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0093-2277 POWDER, FOR SUSPENSION 28.50 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0093-2279 POWDER, FOR SUSPENSION 57 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0093-2279 POWDER, FOR SUSPENSION 57 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0093-8675 POWDER, FOR SUSPENSION 42.90 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0093-8675 POWDER, FOR SUSPENSION 42.90 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0143-9249 TABLET 125 mg ORAL ANDA 28 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0143-9853 SUSPENSION 42.90 mg ORAL ANDA 28 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0143-9981 POWDER, FOR SUSPENSION 28.50 mg ORAL ANDA 27 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0143-9982 POWDER, FOR SUSPENSION 57 mg ORAL ANDA 27 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0781-1619 TABLET, CHEWABLE 28.50 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0781-1643 TABLET, CHEWABLE 57 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0781-1831 TABLET, FILM COATED 125 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0781-1852 TABLET, FILM COATED 125 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0781-1874 TABLET, FILM COATED 125 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 3 0781-1943 TABLET, MULTILAYER, EXTENDED RELEASE 62.50 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0781-6102 POWDER, FOR SUSPENSION 28.50 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0781-6104 POWDER, FOR SUSPENSION 57 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 0781-6139 SUSPENSION 42.90 mg ORAL ANDA 26 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 10544-931 TABLET, FILM COATED 125 mg ORAL ANDA 27 sections
Amoxicillin and Clavulanate Potassium HUMAN PRESCRIPTION DRUG LABEL 2 10544-951 TABLET, FILM COATED 125 mg ORAL ANDA 26 sections
AMOXICILLIN AND CLAVULANATE POTASSIUM HUMAN PRESCRIPTION DRUG LABEL 2 16590-019 TABLET, FILM COATED 125 mg ORAL ANDA 26 sections