cilastatin 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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
BA (Bioavailability) 0 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class ACVR2A,ACVR2B,ACVRL1,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,GRK2,GRK3,GSK3B,IKBKB,ITK,JAK1,JAK2,JAK3,KDR,MAP2K6,MAP3K14,MAP3K21,MAP3K7,MAPK10,MAPK7,MAPK9,MAPKAPK2,MTOR,NTRK2,PDK1,PDK2,PDK4,PIK3CB,PIK3CG,PIM2,PLK1,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TGFBR1,TTK,ZAP70 54
kinase-selectivity-class ACVR2B,AXL,BRAF,CDK9,DYRK1B,EIF2AK3,EPHB4,GRK2,JAK2,MAP2K6,MAP3K14,MAPK7,MAPK8,PRKDC,STK33,TEK,TGFBR1 17
pfas-class PFAS structural alert (1 = True, 0 = False) 0

Approvals:

DateAgencyCompanyOrphan
June 23, 2021 PMDA MSD K.K.
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 160.69 33.70 71 1642 152558 90474176
Multiple organ dysfunction syndrome 53.53 33.70 26 1687 68310 90558424
Renal failure 50.06 33.70 31 1682 130976 90495758
Septic shock 40.17 33.70 23 1690 84137 90542597
Generalised tonic-clonic seizure 38.97 33.70 17 1696 34886 90591848
Heparin-induced thrombocytopenia 36.14 33.70 10 1703 5302 90621432

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 130.18 27.48 83 2400 120478 42498374
Septic shock 54.43 27.48 44 2439 91628 42527224
Multiple organ dysfunction syndrome 48.15 27.48 42 2441 96993 42521859
Eosinophilia 33.69 27.48 22 2461 32877 42585975
Pseudomonas infection 33.42 27.48 17 2466 15906 42602946
Toxic epidermal necrolysis 30.14 27.48 19 2464 26731 42592121

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 211.50 28.81 118 3797 221067 110364317
Multiple organ dysfunction syndrome 97.91 28.81 63 3852 151647 110433737
Septic shock 81.41 28.81 57 3858 157471 110427913
Renal failure 61.14 28.81 56 3859 226518 110358866
Generalised tonic-clonic seizure 54.26 28.81 30 3885 54650 110530734
Eosinophilia 47.33 28.81 28 3887 57908 110527476
Pseudomonas infection 44.27 28.81 21 3894 27832 110557552
Thrombocytopenia 42.78 28.81 57 3858 348828 110236556
Toxic epidermal necrolysis 42.66 28.81 26 3889 56701 110528683
Respiratory failure 40.93 28.81 44 3871 215288 110370096
Agranulocytosis 40.63 28.81 26 3889 61734 110523650
Dermatitis exfoliative 39.73 28.81 15 3900 11332 110574052
Sepsis 39.38 28.81 53 3862 327293 110258091
Stevens-Johnson syndrome 36.56 28.81 22 3893 46879 110538505
Haemodialysis 36.48 28.81 16 3899 17703 110567681
Gamma-glutamyltransferase increased 35.91 28.81 24 3891 61285 110524099
Drug reaction with eosinophilia and systemic symptoms 33.95 28.81 26 3889 82069 110503315
Pathogen resistance 33.31 28.81 15 3900 17657 110567727
Pyrexia 32.76 28.81 87 3828 898178 109687206
Disseminated intravascular coagulation 31.23 28.81 19 3896 41267 110544117
Myoclonus 29.72 28.81 17 3898 32981 110552403
Heparin-induced thrombocytopenia 29.10 28.81 12 3903 11412 110573972
Shock 29.05 28.81 20 3895 53568 110531816

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:33282 antibacterial agent
CHEBI has role CHEBI:35441 antiinfective agent
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:35703 xenobiotic
CHEBI has role CHEBI:37670 protease inhibitor
CHEBI has role CHEBI:76926 EC 3.4.13.19 (membrane dipeptidase) inhibitor
CHEBI has role CHEBI:78298 environmental contaminant
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D011480 Protease Inhibitors

Related Drugs by ATC class:

J01DH Carbapenems 10 drugs
betamipronbiapenemdoripenemertapenemimipenemmeropenempanipenemrelebactamtebipenem pivoxilvaborbactam

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 March 21, 2033 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 March 21, 2033 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 March 21, 2033 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 Dec. 9, 2028 NEW PATIENT POPULATION
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
C0008777 UMLSCUI
CHEBI:3697 CHEBI
CIL PDB_CHEM_ID
CHEMBL766 ChEMBL_ID
CHEMBL1201057 ChEMBL_ID
DB01597 DRUGBANK_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
4017968 VANDF
4019679 VANDF
141A6AMN38 INXIGHT DRUGS

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 0006-3514 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 0006-3516 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 0006-3551 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
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 30 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 25 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-322 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS ANDA 25 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-322 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS ANDA 25 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-349 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS ANDA 25 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-349 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS ANDA 25 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-349 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS ANDA 25 sections