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

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
Seizure 262.65 60.13 83 874 24383 2332745
Drug ineffective 145.66 60.13 82 875 101542 2255586
Pathogen resistance 107.35 60.13 21 936 822 2356306
Renal failure 103.05 60.13 38 919 17311 2339817
Septic shock 100.78 60.13 30 927 7024 2350104
Multiple organ dysfunction syndrome 98.41 60.13 30 927 7611 2349517
Sepsis 89.89 60.13 35 922 18453 2338675
Epilepsy 76.18 60.13 22 935 4617 2352511
Product use in unapproved indication 75.60 60.13 27 930 11173 2345955
Pyrexia 72.58 60.13 42 915 53666 2303462
Drug resistance 68.87 60.13 18 939 2606 2354522
Respiratory failure 67.04 60.13 26 931 13502 2343626
Acinetobacter infection 65.85 60.13 11 946 172 2356956
Rash maculo-papular 64.65 60.13 19 938 4233 2352895
Electrocardiogram QT prolonged 60.97 60.13 21 936 7793 2349335
Generalised tonic-clonic seizure 60.27 60.13 19 938 5353 2351775

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
Drug ineffective 258.67 61.26 136 1212 63665 1681768
Seizure 254.10 61.26 96 1252 20345 1725088
Pathogen resistance 215.06 61.26 45 1303 1044 1744389
Multiple organ dysfunction syndrome 169.14 61.26 58 1290 9184 1736249
Drug resistance 147.77 61.26 41 1307 3189 1742244
Septic shock 133.21 61.26 47 1301 8062 1737371
Sepsis 127.29 61.26 58 1290 19380 1726053
Respiratory failure 116.52 61.26 50 1298 14455 1730978
Toxic epidermal necrolysis 94.27 61.26 27 1321 2344 1743089
Electrocardiogram QT prolonged 94.22 61.26 33 1315 5512 1739921
Pyrexia 91.92 61.26 63 1285 46337 1699096
Thrombocytopenia 89.59 61.26 47 1301 21202 1724231
Hepatitis 82.28 61.26 29 1319 4926 1740507
Product use in unapproved indication 80.55 61.26 34 1314 9388 1736045
Klebsiella infection 74.61 61.26 18 1330 797 1744636
Pneumonia 73.61 61.26 55 1293 46127 1699306
Toxic skin eruption 72.84 61.26 21 1327 1862 1743571
Drug reaction with eosinophilia and systemic symptoms 70.39 61.26 26 1322 5044 1740389
Anaemia 70.24 61.26 45 1303 29412 1716021
Treatment failure 70.17 61.26 25 1323 4376 1741057
Fungaemia 68.54 61.26 14 1334 284 1745149
Acute kidney injury 65.58 61.26 46 1302 34898 1710535
Rash erythematous 65.01 61.26 23 1325 3942 1741491
Eosinophilia 63.74 61.26 22 1326 3505 1741928
Aspartate aminotransferase increased 63.61 61.26 30 1318 10726 1734707
Candida infection 63.28 61.26 19 1329 1939 1743494
Diarrhoea 61.97 61.26 53 1295 53799 1691634
Rash 61.37 61.26 46 1302 38647 1706786

Pharmacologic Action:

SourceCodeDescription
ATC J01DH51 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIBACTERIALS FOR SYSTEMIC USE
OTHER BETA-LACTAM ANTIBACTERIALS
Carbapenems
CHEBI has role CHEBI:36047 antibacterial drug
MeSH PA D000900 Anti-Bacterial Agents
MeSH PA D000890 Anti-Infective Agents

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)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
500MG/VIAL RECARBRIO MSD MERCK CO N212819 July 16, 2019 RX POWDER INTRAVENOUS 8487093 Nov. 19, 2029 TREATMENT OF COMPLICATED INTRA-ABDOMINAL INFECTIONS (CIAI)
500MG/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)

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
C0020933 UMLSCUI
D00206 KEGG_DRUG
71OTZ9ZE0A UNII
74431-23-5 SECONDARY_CAS_RN
424285002 SNOMEDCT_US
5690 RXNORM
46558003 SNOMEDCT_US
4869 MMSL
d04401 MMSL
4017969 VANDF
002813 NDDF
CHEBI:471744 CHEBI
CHEMBL148 ChEMBL_ID
CHEMBL43708 ChEMBL_ID
8YF PDB_CHEM_ID
ID1 PDB_CHEM_ID
IM2 PDB_CHEM_ID
DB01598 DRUGBANK_ID
104838 PUBCHEM_CID
D015378 MESH_DESCRIPTOR_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
PRIMAXIN HUMAN PRESCRIPTION DRUG LABEL 2 0006-3514 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS NDA 16 sections
PRIMAXIN HUMAN PRESCRIPTION DRUG LABEL 2 0006-3516 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS NDA 16 sections
PRIMAXIN HUMAN PRESCRIPTION DRUG LABEL 2 0006-3551 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS ANDA 16 sections
PRIMAXIN HUMAN PRESCRIPTION DRUG LABEL 2 0006-3552 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS ANDA 16 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-322 INJECTION, POWDER, FOR SOLUTION 500 mg INTRAVENOUS ANDA 16 sections
Imipenem and Cilastatin HUMAN PRESCRIPTION DRUG LABEL 2 63323-349 INJECTION, POWDER, FOR SOLUTION 250 mg INTRAVENOUS ANDA 16 sections