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

Stem definitionDrug idCAS RN
analogues of penicillanic acid antibiotics modified in the five-membered ring 1426 64221-86-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • imipenem
  • tienamycin
  • imipemide
  • imipenen
  • imipenem hydrate
Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with CILASTATIN, a renal dipeptidase inhibitor.
  • Molecular weight: 299.35
  • Formula: C12H17N3O4S
  • CLOGP: -1.35
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 4
  • TPSA: 113.72
  • ALOGS: -2.64
  • ROTB: 6

  • 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) 10 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 69 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 222.82 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 1 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.24 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 3 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.86 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 0.95 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
June 23, 2021 PMDA MSD K.K.
Feb. 13, 2020 EMA Merck Sharp & Dohme B.V.
Nov. 26, 1985 FDA

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 313.54 20.63 129 8873 25638 53314426
Pathogen resistance 180.87 20.63 60 8942 6500 53333564
Septic shock 152.41 20.63 107 8895 62122 53277942
Multiple organ dysfunction syndrome 127.69 20.63 92 8910 55585 53284479
Seizure 108.49 20.63 121 8881 129388 53210676
Drug reaction with eosinophilia and systemic symptoms 108.33 20.63 68 8934 32732 53307332
Sepsis 85.47 20.63 114 8888 146315 53193749
Drug resistance 77.72 20.63 46 8956 19916 53320148
Toxic epidermal necrolysis 70.72 20.63 46 8956 23504 53316560
Rash maculo-papular 70.06 20.63 50 8952 29699 53310365
Eosinophilia 67.34 20.63 43 8959 21292 53318772
Acute generalised exanthematous pustulosis 63.06 20.63 32 8970 10249 53329815
Fatigue 60.55 20.63 24 8978 730482 52609582
Acinetobacter infection 58.99 20.63 18 8984 1485 53338579
Delirium 57.45 20.63 51 8951 41378 53298686
Pain 56.33 20.63 15 8987 588383 52751681
Product use in unapproved indication 52.94 20.63 79 8923 112210 53227854
Pseudomonas infection 51.28 20.63 28 8974 10400 53329664
Aplasia 50.94 20.63 21 8981 4171 53335893
Enterococcal infection 50.57 20.63 25 8977 7573 53332491
Agranulocytosis 49.31 20.63 37 8965 23712 53316352
Klebsiella infection 46.66 20.63 24 8978 7902 53332162
Headache 45.44 20.63 17 8985 536804 52803260
Eosinophilic pneumonia acute 44.31 20.63 11 8991 419 53339645
Hepatotoxicity 44.07 20.63 37 8965 27843 53312221
Central nervous system injury 43.43 20.63 9 8993 149 53339915
Respiratory failure 42.15 20.63 67 8935 100445 53239619
Acute respiratory distress syndrome 41.15 20.63 33 8969 23299 53316765
Tic 39.51 20.63 13 8989 1369 53338695
Thrombocytopenia 39.46 20.63 78 8924 138649 53201415
Mycobacterium abscessus infection 39.39 20.63 11 8991 664 53339400
Arthralgia 38.77 20.63 13 8989 439770 52900294
Pyrexia 38.62 20.63 152 8850 403041 52937023
Geotrichum infection 38.41 20.63 10 8992 462 53339602
Generalised tonic-clonic seizure 37.09 20.63 34 8968 28724 53311340
Fall 36.45 20.63 8 8994 358432 52981632
Dermatitis exfoliative 35.02 20.63 18 8984 5918 53334146
Muscle twitching 35.01 20.63 26 8976 16400 53323664
Splenic injury 34.47 20.63 8 8994 228 53339836
Liver injury 34.24 20.63 29 8973 22074 53317990
Hyperchloraemia 33.83 20.63 10 8992 740 53339324
Acute kidney injury 33.10 20.63 106 8896 253762 53086302
Clostridium difficile colitis 32.83 20.63 27 8975 19738 53320326
Hypochromasia 32.14 20.63 8 8994 308 53339756
Inflammatory marker increased 31.48 20.63 17 8985 6173 53333891
Aspergillus infection 31.08 20.63 18 8984 7478 53332586
Malaise 30.76 20.63 11 8991 357606 52982458
Toxic skin eruption 30.73 20.63 22 8980 13117 53326947
Hepatitis fulminant 30.47 20.63 14 8988 3605 53336459
Bone marrow failure 30.18 20.63 31 8971 30084 53309980
Renal failure 29.42 20.63 63 8939 118389 53221675
Bronchopulmonary aspergillosis 28.67 20.63 18 8984 8647 53331417
Granulomatous liver disease 28.61 20.63 9 8993 821 53339243
Clostridium difficile infection 28.47 20.63 29 8973 27864 53312200
Granulomatosis with polyangiitis 27.46 20.63 11 8991 2028 53338036
Cross sensitivity reaction 27.22 20.63 11 8991 2076 53337988
Guillain-Barre syndrome 26.85 20.63 13 8989 3762 53336302
Anisocytosis 26.83 20.63 8 8994 610 53339454
Fungaemia 26.77 20.63 11 8991 2166 53337898
Disorganised speech 26.47 20.63 9 8993 1048 53339016
Systemic candida 26.29 20.63 12 8990 3045 53337019
Electrocardiogram QT prolonged 25.57 20.63 39 8963 56364 53283700
Ototoxicity 25.28 20.63 9 8993 1201 53338863
Disseminated intravascular coagulation 24.82 20.63 23 8979 19696 53320368
Dermatitis bullous 24.63 20.63 16 8986 8147 53331917
Type IV hypersensitivity reaction 24.52 20.63 11 8991 2681 53337383
Megacolon 24.40 20.63 10 8992 1956 53338108
Nocardiosis 24.29 20.63 10 8992 1977 53338087
Drug level below therapeutic 24.00 20.63 12 8990 3721 53336343
Nephropathy toxic 23.91 20.63 16 8986 8556 53331508
Drug eruption 23.65 20.63 25 8977 25069 53314995
Deafness 23.51 20.63 21 8981 17155 53322909
Pneumonia klebsiella 23.45 20.63 10 8992 2159 53337905
Hypersensitivity 22.86 20.63 4 8998 210661 53129403
Cholestasis 22.57 20.63 26 8976 28669 53311395
Pseudomembranous colitis 22.41 20.63 11 8991 3280 53336784
Nasopharyngitis 22.35 20.63 3 8999 192292 53147772
Abdominal discomfort 22.31 20.63 5 8997 221057 53119007
Back pain 22.28 20.63 6 8996 234241 53105823
Hepatic infarction 22.07 20.63 7 8995 656 53339408
Hepatic function abnormal 21.87 20.63 29 8973 36870 53303194
Moraxella infection 21.51 20.63 6 8996 361 53339703
Escherichia infection 21.15 20.63 17 8985 12033 53328031
Constipation 21.03 20.63 4 8998 198408 53141656
Pain in extremity 20.95 20.63 11 8991 285039 53055025

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 275.20 17.79 147 12911 21962 32478506
Pathogen resistance 250.50 17.79 106 12952 9404 32491064
Septic shock 156.04 17.79 164 12894 68825 32431643
Drug resistance 150.28 17.79 101 12957 22864 32477604
Multiple organ dysfunction syndrome 145.54 17.79 159 12899 69695 32430773
Eosinophilia 113.43 17.79 88 12970 24870 32475598
Toxic epidermal necrolysis 105.49 17.79 78 12980 20515 32479953
Rash maculo-papular 92.30 17.79 82 12976 27940 32472528
Thrombocytopenia 88.30 17.79 188 12870 148111 32352357
Drug ineffective 83.00 17.79 338 12720 383139 32117329
Toxic skin eruption 80.56 17.79 53 13005 11561 32488907
Product use in unapproved indication 79.86 17.79 133 12925 87071 32413397
Drug reaction with eosinophilia and systemic symptoms 78.30 17.79 80 12978 32405 32468063
Seizure 75.30 17.79 143 12915 103711 32396757
Ototoxicity 74.40 17.79 27 13031 1585 32498883
Fatigue 68.11 17.79 28 13030 350673 32149795
Nocardiosis 64.45 17.79 31 13027 3700 32496768
Pseudomonas infection 60.23 17.79 45 13013 12011 32488457
Sepsis 55.99 17.79 165 12893 158669 32341799
Respiratory failure 54.81 17.79 128 12930 107054 32393414
Klebsiella infection 54.19 17.79 36 13022 7976 32492492
Hepatic cytolysis 52.91 17.79 36 13022 8297 32492171
Deafness neurosensory 51.03 17.79 24 13034 2724 32497744
Graft versus host disease 51.02 17.79 39 13019 10767 32489701
Mycobacterium abscessus infection 50.61 17.79 16 13042 614 32499854
Fungaemia 49.71 17.79 23 13035 2516 32497952
Fall 48.34 17.79 10 13048 196191 32304277
Electrocardiogram QT prolonged 45.31 17.79 67 12991 39574 32460894
Candida infection 45.30 17.79 44 13014 16759 32483709
Acute respiratory distress syndrome 44.85 17.79 53 13005 25200 32475268
Disseminated intravascular coagulation 41.76 17.79 49 13009 23127 32477341
Pain 41.44 17.79 12 13046 187544 32312924
Delirium 41.35 17.79 68 12990 43978 32456490
Bronchopulmonary aspergillosis 41.01 17.79 38 13020 13649 32486819
Disorganised speech 40.43 17.79 14 13044 716 32499752
Generalised tonic-clonic seizure 39.47 17.79 45 13013 20594 32479874
Agranulocytosis 37.98 17.79 47 13011 23430 32477038
Dizziness 37.07 17.79 19 13039 209599 32290869
Geotrichum infection 36.71 17.79 12 13046 513 32499955
Venoocclusive disease 36.20 17.79 19 13039 2727 32497741
Brain abscess 35.02 17.79 19 13039 2915 32497553
Headache 34.36 17.79 18 13040 196179 32304289
Pseudomembranous colitis 34.20 17.79 19 13039 3053 32497415
Arthralgia 33.70 17.79 9 13049 148439 32352029
Dysphoria 33.37 17.79 17 13041 2294 32498174
Botulism 33.12 17.79 9 13049 201 32500267
Enterococcal infection 32.57 17.79 28 13030 9119 32491349
Pancytopenia 32.28 17.79 95 12963 91140 32409328
Vascular pseudoaneurysm thrombosis 31.75 17.79 7 13051 62 32500406
Treatment failure 30.90 17.79 56 13002 39107 32461361
Clostridium difficile colitis 30.41 17.79 33 13025 14298 32486170
Muscle twitching 29.48 17.79 26 13032 8758 32491710
Incision site pain 29.46 17.79 15 13043 2022 32498446
Cardiac valve vegetation 28.64 17.79 10 13048 524 32499944
Pyrexia 28.21 17.79 222 12836 319746 32180722
Clostridium test positive 27.64 17.79 15 13043 2302 32498166
Tuberculosis 27.64 17.79 25 13033 8704 32491764
Enterococcus test positive 27.01 17.79 11 13047 883 32499585
Completed suicide 26.65 17.79 3 13055 92514 32407954
Back pain 26.62 17.79 6 13052 111047 32389421
Hypoalbuminaemia 26.46 17.79 28 13030 11794 32488674
Condition aggravated 26.41 17.79 128 12930 155533 32344935
Hepatotoxicity 25.49 17.79 35 13023 19302 32481166
Fungal test positive 24.98 17.79 9 13049 517 32499951
Hepatitis cholestatic 24.95 17.79 23 13035 8202 32492266
Splenic candidiasis 24.91 17.79 6 13052 81 32500387
Status epilepticus 24.35 17.79 27 13031 11979 32488489
Asthenia 24.05 17.79 36 13022 235908 32264560
Syncope 23.43 17.79 4 13054 90120 32410348
Mental disorder 23.32 17.79 29 13029 14519 32485949
Leukocytosis 23.05 17.79 37 13021 23430 32477038
Functional gastrointestinal disorder 22.59 17.79 13 13045 2233 32498235
Rash erythematous 22.51 17.79 37 13021 23902 32476566
Partial seizures 21.86 17.79 16 13042 4134 32496334
Acoustic neuroma 21.71 17.79 6 13052 143 32500325
Escherichia infection 21.68 17.79 20 13038 7140 32493328
Mucormycosis 21.55 17.79 18 13040 5636 32494832
Neurological symptom 21.41 17.79 15 13043 3620 32496848
Hyperlactacidaemia 21.24 17.79 14 13044 3060 32497408
Dehydration 20.88 17.79 13 13045 128945 32371523
Tic 20.74 17.79 12 13046 2082 32498386
Dermatitis exfoliative generalised 20.33 17.79 14 13044 3287 32497181
Toxicity to various agents 20.32 17.79 25 13033 178016 32322452
Cerebrovascular accident 20.02 17.79 5 13053 86315 32414153
Gait disturbance 19.97 17.79 4 13054 80404 32420064
Drug eruption 19.90 17.79 31 13027 19135 32481333
Myocardial infarction 19.89 17.79 13 13045 125663 32374805
Megacolon 19.68 17.79 11 13047 1787 32498681
Pneumonia klebsiella 19.59 17.79 13 13045 2872 32497596
Pulmonary physical examination abnormal 19.37 17.79 4 13054 25 32500443
Liver injury 19.35 17.79 26 13032 14048 32486420
Psychiatric symptom 19.26 17.79 14 13044 3580 32496888
Immunosuppressant drug level increased 18.82 17.79 16 13042 5129 32495339
Haemophagocytic lymphohistiocytosis 18.82 17.79 23 13035 11312 32489156
Constipation 18.78 17.79 14 13044 126359 32374109
Osmotic demyelination syndrome 18.56 17.79 8 13050 740 32499728
Antimicrobial susceptibility test resistant 18.41 17.79 6 13052 254 32500214
Acinetobacter test positive 17.98 17.79 5 13053 122 32500346
Peripheral swelling 17.83 17.79 3 13055 68342 32432126

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
MeSH PA D000900 Anti-Bacterial Agents
MeSH PA D000890 Anti-Infective Agents
CHEBI has role CHEBI:36047 antibacterial drugs

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 Acinetobacter spp resistant to carbapenem antimicrobial drugs indication 840588006
Infection caused by Citrobacter spp resistant to carbapenem antimicrobial drugs indication 1137353009
Gram-Negative Aerobic Bacillary Pneumonia indication
Enterobacter Pneumonia indication
Diabetic Foot Infection indication
Inflammatory Disease of Female Pelvic Organs 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
Pseudomonas Respiratory Tract Infection in Cystic Fibrosis off-label use
Clostridium Perfringens Empyema 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 2.9 acidic
pKa2 9.92 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
Bacterial penicillin-binding protein Enzyme INHIBITOR CHEMBL CHEMBL
Penicillin-binding protein 4 Enzyme IC50 7.30 WOMBAT-PK
Penicillin-binding protein 1 Enzyme IC50 7 WOMBAT-PK
Beta-lactamase Enzyme Ki 7.22 CHEMBL
Beta-lactamase GES-13 Enzyme IC50 6.82 CHEMBL

External reference:

IDSource
4017969 VUID
N0000146319 NUI
D00206 KEGG_DRUG
4017969 VANDF
C0020933 UMLSCUI
CHEBI:51799 CHEBI
ID1 PDB_CHEM_ID
CHEMBL43708 ChEMBL_ID
CHEMBL148 ChEMBL_ID
DB01598 DRUGBANK_ID
D015378 MESH_DESCRIPTOR_UI
104838 PUBCHEM_CID
10821 IUPHAR_LIGAND_ID
74431-23-5 SECONDARY_CAS_RN
71OTZ9ZE0A UNII
5690 RXNORM
4869 MMSL
d04401 MMSL
002813 NDDF
424285002 SNOMEDCT_US
46558003 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
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