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
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
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
Epilepsy 361.34 22.23 126 5507 25641 53317792
Pathogen resistance 123.07 22.23 40 5593 6520 53336913
Drug reaction with eosinophilia and systemic symptoms 117.75 22.23 61 5572 32739 53310694
Seizure 111.30 22.23 99 5534 129410 53214023
Septic shock 88.55 22.23 64 5569 62165 53281268
Delirium 73.94 22.23 49 5584 41380 53302053
Multiple organ dysfunction syndrome 69.62 22.23 53 5580 55624 53287809
Eosinophilia 68.92 22.23 37 5596 21298 53322135
Rash maculo-papular 67.60 22.23 41 5592 29708 53313725
Acute generalised exanthematous pustulosis 67.43 22.23 29 5604 10252 53333181
Toxic epidermal necrolysis 54.89 22.23 33 5600 23517 53319916
Muscle twitching 46.18 22.23 26 5607 16400 53327033
Tic 45.53 22.23 13 5620 1369 53342064
Product use in unapproved indication 44.54 22.23 57 5576 112232 53231201
Agranulocytosis 42.13 22.23 28 5605 23721 53319712
Generalised tonic-clonic seizure 41.82 22.23 30 5603 28728 53314705
Acinetobacter infection 40.08 22.23 12 5621 1491 53341942
Dermatitis exfoliative 39.76 22.23 17 5616 5919 53337514
Mycobacterium abscessus infection 39.52 22.23 10 5623 665 53342768
Central nervous system injury 35.30 22.23 7 5626 151 53343282
Klebsiella infection 35.05 22.23 17 5616 7909 53335524
Sepsis 34.31 22.23 58 5575 146371 53197062
Pain 34.11 22.23 10 5623 588388 52755045
Pseudomonas infection 33.42 22.23 18 5615 10410 53333023
Fatigue 33.25 22.23 18 5615 730488 52612945
Granulomatous liver disease 32.78 22.23 9 5624 821 53342612
Enterococcal infection 32.71 22.23 16 5617 7582 53335851
Splenic injury 32.50 22.23 7 5626 229 53343204
Drug eruption 31.58 22.23 24 5609 25070 53318363
Pyrexia 30.90 22.23 103 5530 403090 52940343
Cholestasis 30.83 22.23 25 5608 28670 53314763
Disorganised speech 30.63 22.23 9 5624 1048 53342385
Hypochromasia 30.46 22.23 7 5626 309 53343124
Arthralgia 30.45 22.23 5 5628 439778 52903655
Hepatitis fulminant 29.76 22.23 12 5621 3607 53339826
Headache 29.53 22.23 10 5623 536811 52806622
Guillain-Barre syndrome 29.27 22.23 12 5621 3763 53339670
Hyperchloraemia 29.01 22.23 8 5625 742 53342691
Acute respiratory distress syndrome 28.67 22.23 22 5611 23310 53320123
Liver injury 27.50 22.23 21 5612 22082 53321351
Thrombocytopenia 27.39 22.23 51 5582 138676 53204757
Fall 27.35 22.23 3 5630 358437 52984996
Respiratory failure 26.48 22.23 42 5591 100470 53242963
Dermatitis bullous 25.90 22.23 14 5619 8149 53335284
Anisocytosis 25.80 22.23 7 5626 611 53342822
Hepatic function abnormal 25.41 22.23 25 5608 36874 53306559
Dysphoria 25.25 22.23 12 5621 5337 53338096
Drug resistance 24.91 22.23 19 5614 19943 53323490
Aplasia 24.80 22.23 11 5622 4181 53339252
Toxic skin eruption 24.53 22.23 16 5617 13123 53330310
Pseudomembranous colitis 23.95 22.23 10 5623 3281 53340152
Inflammatory marker increased 23.59 22.23 12 5621 6178 53337255
Stevens-Johnson syndrome 23.46 22.23 20 5613 24562 53318871

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
Epilepsy 335.95 19.44 146 8144 21963 32483273
Pathogen resistance 178.27 19.44 73 8217 9437 32495799
Toxic epidermal necrolysis 101.49 19.44 64 8226 20529 32484707
Seizure 99.21 19.44 127 8163 103727 32401509
Toxic skin eruption 88.79 19.44 48 8242 11566 32493670
Septic shock 79.80 19.44 93 8197 68896 32436340
Drug reaction with eosinophilia and systemic symptoms 69.25 19.44 61 8229 32424 32472812
Drug resistance 67.55 19.44 52 8238 22913 32482323
Delirium 58.78 19.44 64 8226 43982 32461254
Product use in unapproved indication 56.95 19.44 89 8201 87115 32418121
Multiple organ dysfunction syndrome 56.72 19.44 79 8211 69775 32435461
Fatigue 51.71 19.44 13 8277 350688 32154548
Eosinophilia 51.45 19.44 46 8244 24912 32480324
Generalised tonic-clonic seizure 48.51 19.44 41 8249 20598 32484638
Disorganised speech 46.68 19.44 14 8276 716 32504520
Thrombocytopenia 44.52 19.44 109 8181 148190 32357046
Deafness neurosensory 44.42 19.44 19 8271 2729 32502507
Rash maculo-papular 41.40 19.44 43 8247 27979 32477257
Dysphoria 40.76 19.44 17 8273 2294 32502942
Muscle twitching 40.02 19.44 26 8264 8758 32496478
Pseudomembranous colitis 39.23 19.44 18 8272 3054 32502182
Klebsiella infection 37.20 19.44 24 8266 7988 32497248
Status epilepticus 37.07 19.44 28 8262 11978 32493258
Respiratory failure 36.72 19.44 83 8207 107099 32398137
Drug ineffective 36.57 19.44 193 8097 383284 32121952
Agranulocytosis 36.44 19.44 37 8253 23440 32481796
Mental disorder 34.39 19.44 29 8261 14519 32490717
Sepsis 33.88 19.44 103 8187 158731 32346505
Ototoxicity 32.32 19.44 13 8277 1599 32503637
Enterococcus test positive 31.88 19.44 11 8279 883 32504353
Pancytopenia 31.63 19.44 71 8219 91164 32414072
Incision site pain 29.39 19.44 13 8277 2024 32503212
Fall 29.37 19.44 7 8283 196194 32309042
Clostridium test positive 27.79 19.44 13 8277 2304 32502932
Pseudomonas infection 26.39 19.44 23 8267 12033 32493203
Tic 25.89 19.44 12 8278 2082 32503154
Partial seizures 25.84 19.44 15 8275 4135 32501101
Drug eruption 25.80 19.44 28 8262 19138 32486098
Pain 25.61 19.44 8 8282 187548 32317688
Fungal test positive 24.85 19.44 8 8282 518 32504718
Pyrexia 24.47 19.44 152 8138 319816 32185420
Megacolon 24.42 19.44 11 8279 1787 32503449
Dermatitis exfoliative 23.98 19.44 18 8272 7626 32497610
Dermatitis exfoliative generalised 23.44 19.44 13 8277 3288 32501948
Headache 22.46 19.44 11 8279 196186 32309050
Osmotic demyelination syndrome 22.09 19.44 8 8282 740 32504496
Acute generalised exanthematous pustulosis 21.70 19.44 16 8274 6597 32498639
Haemophagocytic lymphohistiocytosis 21.60 19.44 20 8270 11315 32493921
Clostridium difficile colitis 21.17 19.44 22 8268 14309 32490927
Electrocardiogram QT prolonged 21.16 19.44 37 8253 39604 32465632
Dizziness 20.79 19.44 14 8276 209604 32295632
Hepatitis cholestatic 20.69 19.44 17 8273 8208 32497028
Anaphylactic shock 20.30 19.44 22 8268 15012 32490224
Mycobacterium abscessus infection 19.59 19.44 7 8283 623 32504613
Endocarditis 19.58 19.44 15 8275 6549 32498687

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 EC 3.4.13.19 inhibitors
CHEBI has role CHEBI:78298 environmental contaminants
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 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

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
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
2540 RXNORM
32313 MMSL
4447 MMSL
d04402 MMSL
001086 NDDF
004539 NDDF
422591002 SNOMEDCT_US
734464004 SNOMEDCT_US
96058005 SNOMEDCT_US
4017968 VANDF
4019679 VANDF

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
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