cilastatin 🐶 Veterinary Use | 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
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 µM/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
June 23, 2021 PMDA MSD K.K.

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 142.68 28.72 71 1546 117803 50485704
Multiple organ dysfunction syndrome 50.97 28.72 27 1590 50310 50553197
Septic shock 37.22 28.72 23 1594 57152 50546355
Generalised tonic-clonic seizure 35.04 28.72 17 1600 26293 50577214
Renal failure 32.47 28.72 27 1590 106606 50496901
Heparin-induced thrombocytopenia 29.52 28.72 9 1608 3956 50599551
Rash maculo-papular 28.95 28.72 15 1602 26626 50576881

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 124.66 24.88 83 2317 93040 29479087
Septic shock 56.41 24.88 44 2356 62516 29509611
Multiple organ dysfunction syndrome 49.67 24.88 41 2359 63075 29509052
Eosinophilia 32.49 24.88 21 2379 22140 29549987
Toxic epidermal necrolysis 31.12 24.88 19 2381 18134 29553993
Hepatic cytolysis 26.12 24.88 13 2387 8334 29563793
Pseudomonas infection 25.64 24.88 14 2386 10838 29561289

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
Seizure 188.22 26.49 118 3627 166774 64328213
Multiple organ dysfunction syndrome 92.65 26.49 63 3682 101350 64393637
Septic shock 76.65 26.49 57 3688 105380 64389607
Generalised tonic-clonic seizure 49.28 26.49 30 3715 39827 64455160
Eosinophilia 42.86 26.49 27 3718 38049 64456938
Renal failure 41.73 26.49 52 3693 181636 64313351
Toxic epidermal necrolysis 40.95 26.49 26 3719 37140 64457847
Agranulocytosis 40.27 26.49 26 3719 38203 64456784
Thrombocytopenia 34.72 26.49 53 3692 223748 64271239
Pseudomonas infection 34.43 26.49 18 3727 17865 64477122
Dermatitis exfoliative 33.89 26.49 15 3730 10337 64484650
Stevens-Johnson syndrome 32.92 26.49 22 3723 34227 64460760
Sepsis 32.19 26.49 52 3693 230289 64264698
Drug reaction with eosinophilia and systemic symptoms 32.11 26.49 26 3719 54191 64440796
Pathogen resistance 31.13 26.49 15 3730 12528 64482459
Epilepsy 30.94 26.49 21 3724 33510 64461477
Gamma-glutamyltransferase increased 30.30 26.49 24 3721 48486 64446501
Haemodialysis 29.52 26.49 16 3729 17061 64477926
Respiratory failure 29.06 26.49 41 3704 161142 64333845
Disseminated intravascular coagulation 26.89 26.49 19 3726 32329 64462658
Hepatic cytolysis 26.64 26.49 14 3731 14035 64480952

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J01DH51 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIBACTERIALS FOR SYSTEMIC USE
OTHER BETA-LACTAM ANTIBACTERIALS
Carbapenems
ATC J01DH56 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIBACTERIALS FOR SYSTEMIC USE
OTHER BETA-LACTAM ANTIBACTERIALS
Carbapenems
FDA MoA N0000175513 Dipeptidase Inhibitors
FDA EPC N0000175514 Renal Dehydropeptidase Inhibitor
CHEBI has role CHEBI:35703 Xenobiotic
CHEBI has role CHEBI:37670 protease inhibitors
CHEBI has role CHEBI:76926 dipeptide hydrolase inhibitors
CHEBI has role CHEBI:78298 environmental contaminants
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D011480 Protease Inhibitors

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

DiseaseRelationSNOMED_IDDOID
Bacterial septicemia indication 10001005 DOID:0040085
Infection caused by Pseudomonas aeruginosa strain resistant to carbapenem antimicrobial drugs indication 11218009
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
Infection caused by Escherichia coli strain resistant to carbapenem antimicrobial drugs indication 71057007
Infection caused by Serratia spp resistant to carbapenem antimicrobial drugs indication 71120004
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
Infection caused by Enterococcus spp resistant to carbapenem antimicrobial drugs indication 406574007
Acute exacerbation of chronic bronchitis indication 425748003
Infection caused by Klebsiella spp resistant to carbapenem antimicrobial drugs indication 721756002
Infection caused by Acinetobacter spp resistant to carbapenem antimicrobial drugs indication 840588006
Infection caused by Citrobacter spp resistant to carbapenem antimicrobial drugs indication 1137353009
Enterobacter Pneumonia indication
Inflammatory Disease of Female Pelvic Organs 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




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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;500MG/VIAL;250MG/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;500MG/VIAL;250MG/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)
EQ 500MG BASE/VIAL;500MG/VIAL;250MG/VIAL RECARBRIO MSD MERCK CO N212819 July 16, 2019 RX POWDER INTRAVENOUS 8487093 Nov. 19, 2029 TREATMENT OF HOSPITAL-ACQUIRED BACTERIAL PNEUMONIA AND VENTILATOR-ASSOCIATED BACTERIAL PNEUMONIA (HABP/VABP)

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 500MG BASE/VIAL;500MG/VIAL;250MG/VIAL RECARBRIO MSD MERCK CO N212819 July 16, 2019 RX POWDER INTRAVENOUS July 16, 2024 NEW CHEMICAL ENTITY
EQ 500MG BASE/VIAL;500MG/VIAL;250MG/VIAL RECARBRIO MSD MERCK CO N212819 July 16, 2019 RX POWDER INTRAVENOUS July 16, 2029 GENERATING ANTIBIOTIC INCENTIVES NOW

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
D02194 KEGG_DRUG
81129-83-1 SECONDARY_CAS_RN
2540 RXNORM
4017968 VANDF
4019679 VANDF
C0008777 UMLSCUI
CHEBI:3697 CHEBI
CIL PDB_CHEM_ID
CHEMBL766 ChEMBL_ID
DB01597 DRUGBANK_ID
CHEMBL1201057 ChEMBL_ID
D015377 MESH_DESCRIPTOR_UI
6435415 PUBCHEM_CID
5166 IUPHAR_LIGAND_ID
5457 INN_ID
141A6AMN38 UNII
32313 MMSL
4447 MMSL
d04402 MMSL
001086 NDDF
004539 NDDF
422591002 SNOMEDCT_US
734464004 SNOMEDCT_US
96058005 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
PRIMAXINIV HUMAN PRESCRIPTION DRUG LABEL 2 0006-3514 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS NDA 25 sections
PRIMAXINIV HUMAN PRESCRIPTION DRUG LABEL 2 0006-3516 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS NDA 25 sections
PRIMAXINIV HUMAN PRESCRIPTION DRUG LABEL 2 0006-3551 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS ANDA 25 sections
PRIMAXINIV HUMAN PRESCRIPTION DRUG LABEL 2 0006-3552 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS ANDA 25 sections
RECARBRIO HUMAN PRESCRIPTION DRUG LABEL 3 0006-3856 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS NDA 29 sections
RECARBRIO HUMAN PRESCRIPTION DRUG LABEL 3 0006-3856 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS NDA 29 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 44567-705 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS ANDA 24 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 44567-705 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS ANDA 24 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-322 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS ANDA 26 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-322 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS ANDA 26 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-322 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS ANDA 26 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-349 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS ANDA 26 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-349 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS ANDA 26 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-349 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS ANDA 26 sections