cilastatin indications/contra

Stem definitionDrug idCAS RN
enzyme inhibitors 640 82009-34-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • cilastatin
  • cilastatin sodium
  • cilastin
  • cilastatin monosodium
A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, IMIPENEM, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukotriene E4.
  • Molecular weight: 358.45
  • Formula: C16H26N2O5S
  • CLOGP: 0.47
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 4
  • TPSA: 129.72
  • ALOGS: -3.55
  • ROTB: 11

Drug dosage:

DoseUnitRoute
2 g P

Approvals:

DateAgencyCompanyOrphan
Nov. 26, 1985 FDA MERCK

FDA Adverse Event Reporting System

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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
Seizure 581.56 63.79 175 1235 40225 3344224
Multiple organ dysfunction syndrome 169.36 63.79 54 1356 14356 3370093
Sepsis 157.43 63.79 63 1347 32310 3352139
Drug ineffective 154.79 63.79 93 1317 115997 3268452
Pathogen resistance 123.11 63.79 26 1384 1345 3383104
Septic shock 112.11 63.79 38 1372 12146 3372303
Generalised tonic-clonic seizure 106.20 63.79 33 1377 8009 3376440
Treatment failure 99.89 63.79 30 1380 6494 3377955
Thrombocytopenia 96.97 63.79 46 1364 35222 3349227
Pyrexia 94.83 63.79 60 1350 81055 3303394
Drug resistance 91.48 63.79 26 1384 4637 3379812
Toxic skin eruption 87.95 63.79 23 1387 3005 3381444
Drug reaction with eosinophilia and systemic symptoms 82.00 63.79 27 1383 7868 3376581
Respiratory failure 81.85 63.79 36 1374 23105 3361344
Epilepsy 81.26 63.79 26 1384 6919 3377530
Eosinophilia 77.11 63.79 23 1387 4850 3379599
Rash 76.73 63.79 50 1360 70771 3313678
Renal failure 75.57 63.79 38 1372 32902 3351547
Gamma-glutamyltransferase increased 74.29 63.79 26 1384 9102 3375347
Acute generalised exanthematous pustulosis 66.05 63.79 17 1393 2082 3382367
Toxic epidermal necrolysis 65.65 63.79 20 1390 4525 3379924
Pneumonia 65.07 63.79 45 1365 70098 3314351
Rash maculo-papular 64.67 63.79 21 1389 5846 3378603

Pharmacologic Action:

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SourceCodeDescription
ATC J01DH51 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIBACTERIALS FOR SYSTEMIC USE
OTHER BETA-LACTAM ANTIBACTERIALS
Carbapenems
FDA MoA N0000175513 Dipeptidase Inhibitors
FDA EPC N0000175514 Renal Dehydropeptidase Inhibitor
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D011480 Protease Inhibitors

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Bacterial septicemia indication 10001005
Infection of skin AND/OR subcutaneous tissue indication 19824006
Pneumonia due to Streptococcus indication 34020007
Peritonitis indication 48661000
Lower respiratory tract infection indication 50417007
Pneumonia due to Escherichia coli indication 51530003
Bacterial pneumonia indication 53084003 DOID:874
Haemophilus influenzae pneumonia indication 70036007
Abdominal abscess indication 75100008
Endometritis indication 78623009 DOID:1002
Infection of bone indication 111253001
Female genital tract infection indication 125585007
Infectious disease of abdomen indication 128070006
Bacterial infection due to Klebsiella pneumoniae indication 186435004
Bacterial endocarditis indication 301183007
Bacterial urinary infection indication 312124009
Infectious disorder of joint indication 363162000 DOID:381
Acute exacerbation of chronic bronchitis indication 425748003
Gram-Negative Aerobic Bacillary Pneumonia indication
Diabetic Foot Infection indication
Inflammatory Disease of Female Pelvic Organs indication
Enterobacter Pneumonia indication
Kidney disease contraindication 90708001 DOID:2527
Seizure disorder contraindication 128613002 DOID:1826
Lesion of brain contraindication 301766008
Pseudomembranous enterocolitis contraindication 397683000 DOID:0060185
Pyrexia of unknown origin off-label use 7520000
Inhalational anthrax off-label use 11389007
Cutaneous anthrax off-label use 84980006 DOID:7426
Gastrointestinal anthrax off-label use 111798006 DOID:13386
Infection by Campylobacter fetus off-label use 111835002
Gas gangrene caused by clostridium perfringens off-label use 266093005
Anthrax off-label use 409498004 DOID:7427
Melioidosis off-label use 428111003 DOID:5052
Pseudomonas Respiratory Tract Infection in Cystic Fibrosis off-label use
Clostridium Perfringens Empyema off-label use

Acid dissociation constants calculated using MoKa v3.0.0

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Dissociation levelDissociation constantType (acidic/basic)
pKa1 2.08 acidic
pKa2 3.82 acidic
pKa3 12.31 acidic
pKa4 9.35 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Dipeptidase 1 Enzyme INHIBITOR Ki 6.96 WOMBAT-PK CHEMBL
Dipeptidase 1 Enzyme Ki 6.96 CHEMBL

External reference:

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IDSource
5166 IUPHAR_LIGAND_ID
4019679 VUID
N0000147771 NUI
C0008777 UMLSCUI
D02194 KEGG_DRUG
141A6AMN38 UNII
5457 INN_ID
81129-83-1 SECONDARY_CAS_RN
CHEMBL766 ChEMBL_ID
2540 RXNORM
96058005 SNOMEDCT_US
d04402 MMSL
4019679 VANDF
422591002 SNOMEDCT_US
N0000006280 NDFRT
N0000147771 NDFRT
004539 NDDF
6435415 PUBCHEM_CID
CHEMBL1201057 ChEMBL_ID
DB01597 DRUGBANK_ID
D015377 MESH_DESCRIPTOR_UI
CHEBI:3697 CHEBI
CIL PDB_CHEM_ID

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
PRIMAXIN HUMAN PRESCRIPTION DRUG LABEL 2 0006-3514 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS NDA 17 sections
PRIMAXIN HUMAN PRESCRIPTION DRUG LABEL 2 0006-3516 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS NDA 17 sections
PRIMAXIN HUMAN PRESCRIPTION DRUG LABEL 2 0006-3551 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS ANDA 17 sections
PRIMAXIN HUMAN PRESCRIPTION DRUG LABEL 2 0006-3552 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS ANDA 17 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 0409-3507 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS ANDA 18 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 0409-3508 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS ANDA 18 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 55154-9389 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS ANDA 13 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-322 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS ANDA 13 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-349 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS ANDA 13 sections