cilastatin Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

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

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
2 g P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 25 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 70 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 59.78 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution) 0.15 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 2.30 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.60 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 0.86 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Nov. 26, 1985 FDA MERCK

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
Seizure 241.76 82.10 73 657 24393 2332962
Drug ineffective 83.10 82.10 52 678 101572 2255783

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
Seizure 260.12 69.31 90 905 20351 1725435
Pathogen resistance 186.80 69.31 38 957 1051 1744735
Drug ineffective 158.72 69.31 89 906 63712 1682074
Sepsis 110.73 69.31 48 947 19390 1726396
Septic shock 99.51 69.31 35 960 8074 1737712
Multiple organ dysfunction syndrome 98.76 69.31 36 959 9206 1736580
Toxic epidermal necrolysis 88.26 69.31 24 971 2347 1743439
Drug resistance 80.92 69.31 24 971 3206 1742580
Respiratory failure 79.75 69.31 35 960 14470 1731316
Thrombocytopenia 78.74 69.31 39 956 21210 1724576
Pyrexia 76.33 69.31 50 945 46350 1699436
Toxic skin eruption 69.77 69.31 19 976 1864 1743922

Pharmacologic Action:

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)

DiseaseRelationSNOMED_IDDOID
Bacterial septicemia indication 10001005 DOID:0040085
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
Acute exacerbation of chronic bronchitis indication 425748003
Inflammatory Disease of Female Pelvic Organs indication
Enterobacter Pneumonia indication
Diabetic Foot Infection indication
Gram-Negative Aerobic Bacillary Pneumonia indication
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
Clostridium Perfringens Empyema off-label use
Pseudomonas Respiratory Tract Infection in Cystic Fibrosis off-label use
Kidney disease contraindication 90708001 DOID:557
Seizure disorder contraindication 128613002
Lesion of brain contraindication 301766008
Pseudomembranous enterocolitis contraindication 397683000

Acid dissociation constants calculated using MoKa v3.0.0

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)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 500MG BASE/VIAL RECARBRIO MSD MERCK CO N212819 July 16, 2019 RX POWDER INTRAVENOUS 8487093 Nov. 19, 2029 TREATMENT OF COMPLICATED INTRA-ABDOMINAL INFECTIONS (CIAI)
EQ 500MG BASE/VIAL RECARBRIO MSD MERCK CO N212819 July 16, 2019 RX POWDER INTRAVENOUS 8487093 Nov. 19, 2029 TREATMENT OF COMPLICATED URINARY TRACT INFECTIONS, INCLUDING PYELONEPHRITIS (CUTI)

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

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:

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

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
PRIMAXIN HUMAN PRESCRIPTION DRUG LABEL 2 0006-3514 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS NDA 16 sections
PRIMAXIN HUMAN PRESCRIPTION DRUG LABEL 2 0006-3516 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS NDA 16 sections
PRIMAXIN HUMAN PRESCRIPTION DRUG LABEL 2 0006-3551 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS ANDA 16 sections
PRIMAXIN HUMAN PRESCRIPTION DRUG LABEL 2 0006-3552 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS ANDA 16 sections
RECARBRIO HUMAN PRESCRIPTION DRUG LABEL 1 0006-3856 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS NDA 17 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-322 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS ANDA 16 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-349 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS ANDA 16 sections