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

Stem definitionDrug idCAS RN
benzodiazepine receptor antagonists/agonists (benzodiazepine derivatives) 1195 78755-81-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • flumazenil
  • anexate
  • flumazepil
  • mazicon
  • Ro-15-1788
A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses.
  • Molecular weight: 303.29
  • Formula: C15H14FN3O3
  • CLOGP: 1.29
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 0
  • TPSA: 64.43
  • ALOGS: -2.46
  • ROTB: 3

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.13 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.50 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.16 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 16 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.80 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 16 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.58 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 0.78 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Dec. 20, 1991 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
Drug withdrawal convulsions 187.72 54.07 30 722 1311 46683999
Intentional overdose 153.94 54.07 52 700 64892 46620418
Drug dependence 135.15 54.07 36 716 19865 46665445
Intentional product misuse 100.64 54.07 35 717 47093 46638217
Product use issue 76.96 54.07 35 717 94609 46590701
Seizure 59.60 54.07 32 720 123022 46562288

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
Intentional overdose 86.50 38.21 35 793 41446 29910204
Drug withdrawal convulsions 71.27 38.21 14 814 1145 29950505
Coma 63.73 38.21 28 800 40421 29911229
Drug dependence 54.91 38.21 21 807 21274 29930376
Intentional product misuse 51.35 38.21 23 805 34644 29917006
Product use issue 42.24 38.21 22 806 45994 29905656

Pharmacologic Action:

SourceCodeDescription
ATC V03AB25 VARIOUS
ALL OTHER THERAPEUTIC PRODUCTS
ALL OTHER THERAPEUTIC PRODUCTS
Antidotes
FDA EPC N0000175680 Benzodiazepine Antagonist
CHEBI has role CHEBI:65259 gamma-aminobutyric acid receptor antagonists
CHEBI has role CHEBI:90757 antidote to benzodiazepine overdose
MeSH PA D000931 Antidotes
MeSH PA D018682 GABA Agents
MeSH PA D018757 GABA Modulators
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D020011 Protective Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Benzodiazepine Induced Sedation indication
Benzodiazepine Toxicity indication
Benzodiazepine Maintained Anesthesia indication
Anxiety contraindication 48694002
Neuromuscular block, function contraindication 55394004
Heart disease contraindication 56265001 DOID:114
Injury of head contraindication 82271004
Epilepsy contraindication 84757009 DOID:1826
Benzodiazepine dependence contraindication 231473004
Disease of liver contraindication 235856003 DOID:409
Panic disorder contraindication 371631005 DOID:594
Tricyclic Antidepressant Toxicity contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 1.93 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
GABA-A receptor alpha-6/beta-3/gamma-2 Ion channel ALLOSTERIC ANTAGONIST Ki 6.83 WOMBAT-PK CHEMBL
Gamma-aminobutyric acid receptor subunit alpha-4 Ion channel ALLOSTERIC ANTAGONIST Ki 8.70 CHEMBL CHEMBL
GABA-A receptor alpha-1/beta-3/gamma-2 Ion channel ALLOSTERIC ANTAGONIST Ki 9.10 WOMBAT-PK CHEMBL
GABA-A receptor alpha-2/beta-3/gamma-2 Ion channel ALLOSTERIC ANTAGONIST Ki 9.05 WOMBAT-PK CHEMBL
GABA-A receptor alpha-3/beta-3/gamma-2 Ion channel ALLOSTERIC ANTAGONIST Ki 8.98 WOMBAT-PK CHEMBL
GABA-A receptor alpha-5/beta-3/gamma-2 Ion channel ALLOSTERIC ANTAGONIST Ki 9.22 WOMBAT-PK CHEMBL
GABA-A receptor; anion channel Ion channel Ki 9.05 CHEMBL
Gamma-aminobutyric acid receptor subunit alpha-1 Ion channel Kd 8.70 CHEMBL
Gamma-aminobutyric acid receptor subunit alpha-2 Ion channel Ki 8.24 CHEMBL
Gamma-aminobutyric acid receptor subunit alpha-3 Ion channel Ki 8.09 CHEMBL
Gamma-aminobutyric acid receptor subunit alpha-5 Ion channel Kd 9.30 CHEMBL
GABA A receptor alpha-6/beta-2/gamma-2 Ion channel Ki 7.82 CHEMBL
GABA-A receptor; anion channel Ion channel Ki 9.10 CHEMBL
GABA-A receptor; anion channel Ion channel Ki 10.05 CHEMBL
GABA-A receptor; alpha-1/beta-2/gamma-2 Ion channel Ki 9.30 CHEMBL
GABA A receptor alpha-3/beta-2/gamma-2 Ion channel Ki 9.22 CHEMBL

External reference:

IDSource
4020178 VUID
N0000148120 NUI
D00697 KEGG_DRUG
4020178 VANDF
C0591091 UMLSCUI
CHEBI:5103 CHEBI
FYP PDB_CHEM_ID
CHEMBL407 ChEMBL_ID
DB01205 DRUGBANK_ID
D005442 MESH_DESCRIPTOR_UI
3373 PUBCHEM_CID
4192 IUPHAR_LIGAND_ID
5311 INN_ID
40P7XK9392 UNII
4457 RXNORM
4736 MMSL
60236 MMSL
d01407 MMSL
003625 NDDF
387575000 SNOMEDCT_US
96247007 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 0143-9683 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 30 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 0143-9684 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 30 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 0143-9783 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 29 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 0143-9784 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 29 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 0641-6031 INJECTION 0.10 mg INTRAVENOUS ANDA 31 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 0641-6032 INJECTION 0.10 mg INTRAVENOUS ANDA 31 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 36000-148 INJECTION 0.10 mg INTRAVENOUS ANDA 30 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 36000-149 INJECTION 0.10 mg INTRAVENOUS ANDA 30 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 50090-1337 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 29 sections
FLUMAZENIL HUMAN PRESCRIPTION DRUG LABEL 1 51662-1253 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 15 sections
FLUMAZENIL HUMAN PRESCRIPTION DRUG LABEL 1 51662-1254 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 15 sections
FLUMAZENIL HUMAN PRESCRIPTION DRUG LABEL 1 51662-1579 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 14 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 52584-088 INJECTION 0.10 mg INTRAVENOUS ANDA 13 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 52584-089 INJECTION 0.10 mg INTRAVENOUS ANDA 14 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 52584-093 INJECTION 1 mg INTRAVENOUS ANDA 12 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 52584-783 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 12 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 52584-784 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 14 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 54868-5715 INJECTION 0.10 mg INTRAVENOUS ANDA 29 sections
Flumazenil Human Prescription Drug Label 1 63323-424 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 12 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 67457-444 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 17 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 67457-447 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 17 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 70385-2002 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 29 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 70385-2021 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 29 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 71872-7008 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 29 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 71872-7038 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 29 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 71872-7206 INJECTION 0.10 mg INTRAVENOUS ANDA 30 sections