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
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 202.99 21.26 88 6541 23650 46655783
Pathogen resistance 142.04 21.26 47 6582 6013 46673420
Septic shock 117.56 21.26 83 6546 57810 46621623
Multiple organ dysfunction syndrome 84.34 21.26 65 6564 51645 46627788
Drug resistance 71.24 21.26 39 6590 17329 46662104
Drug reaction with eosinophilia and systemic symptoms 68.48 21.26 46 6583 29502 46649931
Sepsis 63.61 21.26 87 6542 135927 46543506
Toxic epidermal necrolysis 59.72 21.26 38 6591 22240 46657193
Acute generalised exanthematous pustulosis 55.56 21.26 27 6602 9378 46670055
Acinetobacter infection 54.18 21.26 16 6613 1406 46678027
Product use in unapproved indication 51.93 21.26 64 6565 90209 46589224
Klebsiella infection 48.21 21.26 22 6607 6640 46672793
Eosinophilic pneumonia acute 48.00 21.26 11 6618 354 46679079
Rash maculo-papular 47.52 21.26 36 6593 27838 46651595
Eosinophilia 47.13 21.26 31 6598 19186 46660247
Pseudomonas infection 45.87 21.26 24 6605 9734 46669699
Central nervous system injury 44.98 21.26 9 6620 149 46679284
Hepatotoxicity 44.18 21.26 33 6596 24976 46654457
Enterococcal infection 44.12 21.26 21 6608 6966 46672467
Fatigue 42.15 21.26 17 6612 608680 46070753
Mycobacterium abscessus infection 42.10 21.26 11 6618 615 46678818
Geotrichum infection 40.13 21.26 10 6619 462 46678971
Headache 39.02 21.26 10 6619 478342 46201091
Tic 38.89 21.26 12 6617 1224 46678209
Liver injury 37.27 21.26 25 6604 15976 46663457
Pain 36.97 21.26 11 6618 476937 46202496
Splenic injury 36.58 21.26 8 6621 207 46679226
Hyperchloraemia 36.32 21.26 10 6619 683 46678750
Inflammatory marker increased 36.24 21.26 17 6612 5458 46673975
Hypochromasia 34.15 21.26 8 6621 284 46679149
Hepatitis fulminant 33.63 21.26 14 6615 3388 46676045
Clostridium difficile infection 33.32 21.26 28 6601 25075 46654358
Respiratory failure 33.21 21.26 53 6576 94763 46584670
Acute respiratory distress syndrome 32.34 21.26 26 6603 21896 46657537
Granulomatosis with polyangiitis 30.64 21.26 11 6618 1791 46677642
Guillain-Barre syndrome 30.60 21.26 13 6616 3309 46676124
Electrocardiogram QT prolonged 30.47 21.26 37 6592 51288 46628145
Granulomatous liver disease 30.19 21.26 9 6620 817 46678616
Agranulocytosis 29.97 21.26 25 6604 22160 46657273
Muscle twitching 29.63 21.26 21 6608 14651 46664782
Delirium 29.17 21.26 31 6598 37197 46642236
Anisocytosis 28.62 21.26 8 6621 578 46678855
Fall 28.54 21.26 6 6623 329091 46350342
Toxic skin eruption 28.00 21.26 19 6610 12368 46667065
Ototoxicity 27.90 21.26 9 6620 1060 46678373
Acute kidney injury 27.86 21.26 85 6544 235770 46443663
Aspergillus infection 26.94 21.26 15 6614 6875 46672558
Malaise 26.82 21.26 7 6622 331225 46348208
Aplasia 26.47 21.26 12 6617 3564 46675869
Nephropathy toxic 25.84 21.26 15 6614 7439 46671994
Drug level below therapeutic 24.73 21.26 11 6618 3126 46676307
Megacolon 23.86 21.26 9 6620 1682 46677751
Clostridium difficile colitis 23.20 21.26 20 6609 18533 46660900
Bronchopulmonary aspergillosis 23.15 21.26 14 6615 7482 46671951
Pyrexia 22.91 21.26 104 6525 348698 46330735
Systemic candida 22.91 21.26 10 6619 2717 46676716
Moraxella infection 22.60 21.26 6 6623 357 46679076
Renal injury 22.44 21.26 15 6614 9526 46669907
Fungaemia 22.43 21.26 9 6620 1982 46677451
Arthralgia 22.35 21.26 12 6617 364591 46314842
Pneumonia klebsiella 22.14 21.26 9 6620 2050 46677383
Bone marrow failure 22.00 21.26 24 6605 29645 46649788

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
Pathogen resistance 256.90 18.50 98 9545 8312 29934523
Epilepsy 183.14 18.50 101 9542 20068 29922767
Drug resistance 137.99 18.50 84 9559 20049 29922786
Septic shock 102.66 18.50 114 9529 63493 29879342
Multiple organ dysfunction syndrome 101.11 18.50 113 9530 63374 29879461
Product use in unapproved indication 90.68 18.50 115 9528 73578 29869257
Toxic epidermal necrolysis 88.73 18.50 61 9582 17879 29924956
Ototoxicity 79.99 18.50 26 9617 1370 29941465
Nocardiosis 70.00 18.50 30 9613 3425 29939410
Toxic skin eruption 65.44 18.50 42 9601 10973 29931862
Klebsiella infection 61.09 18.50 34 9609 6853 29935982
Drug reaction with eosinophilia and systemic symptoms 58.27 18.50 58 9585 28430 29914405
Rash maculo-papular 58.09 18.50 55 9588 25363 29917472
Drug ineffective 57.83 18.50 239 9404 340148 29602687
Thrombocytopenia 57.18 18.50 132 9511 136912 29805923
Eosinophilia 56.55 18.50 51 9592 22109 29920726
Graft versus host disease 56.12 18.50 37 9606 10113 29932722
Mycobacterium abscessus infection 55.19 18.50 16 9627 572 29942263
Electrocardiogram QT prolonged 53.93 18.50 62 9581 35773 29907062
Fungaemia 47.27 18.50 20 9623 2211 29940624
Respiratory failure 46.48 18.50 101 9542 100541 29842294
Candida infection 44.49 18.50 38 9605 15324 29927511
Fatigue 43.10 18.50 25 9618 320648 29622187
Geotrichum infection 40.39 18.50 12 9631 468 29942367
Fall 36.82 18.50 7 9636 181865 29760970
Pseudomonas infection 36.79 18.50 29 9614 10453 29932382
Venoocclusive disease 35.10 18.50 17 9626 2573 29940262
Botulism 35.09 18.50 9 9634 201 29942634
Disseminated intravascular coagulation 34.42 18.50 39 9604 22132 29920703
Acute respiratory distress syndrome 34.27 18.50 40 9603 23432 29919403
Tuberculosis 34.21 18.50 25 9618 8052 29934783
Sepsis 34.06 18.50 114 9529 146281 29796554
Vascular pseudoaneurysm thrombosis 33.30 18.50 7 9636 62 29942773
Incision site pain 32.85 18.50 15 9628 1989 29940846
Pain 32.19 18.50 8 9635 172633 29770202
Brain abscess 31.59 18.50 16 9627 2665 29940170
Splenic candidiasis 31.29 18.50 7 9636 85 29942750
Dizziness 31.03 18.50 12 9631 194897 29747938
Arthralgia 30.23 18.50 4 9639 135787 29807048
Hepatotoxicity 30.02 18.50 33 9610 18112 29924723
Enterococcus test positive 29.89 18.50 11 9632 841 29941994
Muscle twitching 29.56 18.50 23 9620 8132 29934703
Clostridium test positive 29.40 18.50 14 9629 2042 29940793
Pancytopenia 29.09 18.50 76 9567 84976 29857859
Cardiac valve vegetation 28.02 18.50 9 9634 456 29942379
Headache 27.76 18.50 12 9631 182294 29760541
Deafness neurosensory 27.38 18.50 14 9629 2379 29940456
Hypoalbuminaemia 27.25 18.50 25 9618 11067 29931768
Clostridium difficile colitis 26.09 18.50 26 9617 12742 29930093
Hepatitis cholestatic 25.96 18.50 21 9622 7851 29934984
Rash erythematous 25.91 18.50 34 9609 22418 29920417
Dermatitis exfoliative generalised 25.24 18.50 14 9629 2801 29940034
Neurological symptom 25.18 18.50 15 9628 3432 29939403
Enterococcal infection 25.15 18.50 21 9622 8203 29934632
Agranulocytosis 24.97 18.50 33 9610 21909 29920926
Treatment failure 24.86 18.50 42 9601 34637 29908198
Functional gastrointestinal disorder 23.53 18.50 12 9631 2027 29940808
Acoustic neuroma 23.39 18.50 6 9637 134 29942701
Immunosuppressant drug level increased 23.25 18.50 16 9627 4686 29938149
Bronchopulmonary aspergillosis 23.25 18.50 24 9619 12260 29930575
Dysphoria 22.94 18.50 12 9631 2136 29940699
Psychiatric symptom 22.86 18.50 14 9629 3365 29939470
Completed suicide 21.97 18.50 3 9640 99489 29843346
Mucormycosis 21.62 18.50 16 9627 5252 29937583
Delirium 21.30 18.50 43 9600 40588 29902247
Haemoperitoneum 21.02 18.50 10 9633 1455 29941380
Osmotic demyelination syndrome 20.94 18.50 8 9635 678 29942157
Tic 20.71 18.50 11 9632 2021 29940814
Pyrexia 20.38 18.50 163 9480 294326 29648509
Pulmonary physical examination abnormal 20.25 18.50 4 9639 25 29942810
Generalised tonic-clonic seizure 20.11 18.50 28 9615 19523 29923312
Off label use 20.06 18.50 143 9500 249147 29693688
Clostridium difficile infection 19.94 18.50 25 9618 15758 29927077
Status epilepticus 19.82 18.50 21 9622 11051 29931784
Pseudomembranous colitis 19.71 18.50 12 9631 2856 29939979
Fungal test positive 19.45 18.50 7 9636 502 29942333
Citrobacter infection 19.32 18.50 7 9636 512 29942323
Partial seizures 19.06 18.50 13 9630 3754 29939081
Bone marrow failure 18.66 18.50 34 9609 29751 29913084
Back pain 18.63 18.50 5 9638 102591 29840244

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 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
Diabetic Foot Infection indication
Gram-Negative Aerobic Bacillary Pneumonia indication
Enterobacter Pneumonia 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)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Bacterial penicillin-binding protein Enzyme INHIBITOR CHEMBL CHEMBL
Beta-lactamase GES-13 Enzyme IC50 6.82 CHEMBL
Beta-lactamase Enzyme Ki 7.22 CHEMBL
Penicillin-binding protein 1 Enzyme IC50 7 WOMBAT-PK
Penicillin-binding protein 4 Enzyme IC50 7.30 WOMBAT-PK

External reference:

IDSource
4017969 VUID
N0000146319 NUI
D00206 KEGG_DRUG
74431-23-5 SECONDARY_CAS_RN
4017969 VANDF
C0020933 UMLSCUI
CHEBI:51799 CHEBI
ID1 PDB_CHEM_ID
CHEMBL43708 ChEMBL_ID
CHEMBL148 ChEMBL_ID
DB01598 DRUGBANK_ID
D015378 MESH_DESCRIPTOR_UI
10821 IUPHAR_LIGAND_ID
71OTZ9ZE0A UNII
104838 PUBCHEM_CID
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