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

Stem definitionDrug idCAS RN
diazepam derivatives 2729 28911-01-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • triazolam
  • U-33,030
  • U 33,030
  • U33,030
A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries.
  • Molecular weight: 343.21
  • Formula: C17H12Cl2N4
  • CLOGP: 2.62
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 0
  • TPSA: 43.07
  • ALOGS: -4.27
  • ROTB: 1

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
0.25 mg O
0.20 mg SL

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.05 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 2 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.02 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 44 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.58 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) 0.10 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 2.70 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Nov. 15, 1982 FDA PHARMACIA AND UPJOHN

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
Sopor 494.29 15.56 173 8706 19655 46657528
Drug abuse 372.94 15.56 199 8680 63209 46613974
Suicide attempt 178.97 15.56 118 8761 54918 46622265
Overdose 171.06 15.56 147 8732 101832 46575351
Intentional self-injury 162.12 15.56 83 8796 24083 46653100
Intentional overdose 103.44 15.56 91 8788 64853 46612330
Coma 75.83 15.56 73 8806 58276 46618907
Altered state of consciousness 66.08 15.56 46 8833 23302 46653881
Hepatic function abnormal 64.51 15.56 53 8826 34368 46642815
Loss of consciousness 62.15 15.56 89 8790 108149 46569034
Depressed level of consciousness 51.64 15.56 54 8825 47515 46629668
Corneal epithelium defect 45.29 15.56 11 8868 338 46676845
Anterior chamber cell 39.84 15.56 11 8868 564 46676619
Punctate keratitis 39.32 15.56 11 8868 592 46676591
Blood creatine phosphokinase increased 34.69 15.56 34 8845 27690 46649493
Liver disorder 31.30 15.56 37 8842 37209 46639974
Purpura senile 29.93 15.56 9 8870 626 46676557
Somnolence 29.00 15.56 80 8799 156441 46520742
Corneal oedema 28.47 15.56 11 8868 1635 46675548
Hyponatraemic encephalopathy 27.75 15.56 7 8872 252 46676931
Neuroleptic malignant syndrome 27.07 15.56 20 8859 11102 46666081
Hypokinesia 26.75 15.56 20 8859 11302 46665881
Application site injury 26.34 15.56 5 8874 45 46677138
Postoperative delirium 25.68 15.56 5 8874 52 46677131
Tarsal tunnel syndrome 25.43 15.56 8 8871 647 46676536
Blepharospasm 25.04 15.56 11 8868 2263 46674920
Bradykinesia 24.77 15.56 13 8866 3953 46673230
Bradyphrenia 24.27 15.56 15 8864 6215 46670968
Blood lactate dehydrogenase increased 23.54 15.56 24 8855 20476 46656707
Dependence 23.42 15.56 10 8869 1921 46675262
Vestibular disorder 23.17 15.56 9 8870 1357 46675826
Delusion 22.58 15.56 18 8861 11170 46666013
Rheumatoid arthritis 22.14 15.56 9 8870 240206 46436977
Application site ulcer 21.54 15.56 5 8874 126 46677057
Resorption bone increased 21.18 15.56 8 8871 1119 46676064
Fatigue 20.80 15.56 54 8825 608643 46068540
Peripheral swelling 20.19 15.56 3 8876 158068 46519115
Drug eruption 19.27 15.56 22 8857 21307 46655876
Drug interaction 19.23 15.56 83 8796 203011 46474172
Alcohol interaction 18.14 15.56 9 8870 2436 46674747
Hyperventilation 18.04 15.56 12 8867 5635 46671548
Syncope 17.85 15.56 52 8827 104751 46572432
Product dose omission issue 17.80 15.56 5 8874 168515 46508668
Electrocardiogram T wave inversion 17.72 15.56 10 8869 3506 46673677
Blood alkaline phosphatase increased 17.65 15.56 29 8850 39580 46637603
Delirium 17.60 15.56 28 8851 37200 46639983
Aspartate aminotransferase increased 17.39 15.56 43 8836 78657 46598526
Torsade de pointes 17.28 15.56 16 8863 12138 46665045
Interstitial lung disease 17.03 15.56 34 8845 53915 46623268
Intentional product misuse 16.46 15.56 31 8848 47097 46630086
Rhabdomyolysis 16.45 15.56 29 8850 41880 46635303

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
Sopor 230.79 15.56 88 6539 10903 29934948
Drug abuse 121.76 15.56 118 6509 81954 29863897
Intentional overdose 85.79 15.56 72 6555 41409 29904442
Suicide attempt 72.38 15.56 62 6565 36635 29909216
Blood creatine phosphokinase increased 55.59 15.56 58 6569 43790 29902061
Depressed level of consciousness 54.73 15.56 54 6573 38168 29907683
Intentional self-injury 54.13 15.56 35 6592 13497 29932354
Altered state of consciousness 44.09 15.56 36 6591 19883 29925968
Neuroleptic malignant syndrome 41.53 15.56 32 6595 16263 29929588
Overdose 40.09 15.56 69 6558 84268 29861583
Somnolence 39.40 15.56 74 6553 96689 29849162
Hepatic function abnormal 38.63 15.56 47 6580 41898 29903953
Interstitial lung disease 29.56 15.56 50 6577 60147 29885704
Drug dependence 28.46 15.56 29 6598 21266 29924585
Loss of consciousness 24.32 15.56 54 6573 79321 29866530
Road traffic accident 24.19 15.56 24 6603 17047 29928804
Bradyphrenia 22.96 15.56 13 6614 3944 29941907
Blood lactate dehydrogenase increased 22.14 15.56 25 6602 20576 29925275
Gamma-glutamyltransferase increased 20.93 15.56 29 6598 29321 29916530
Rhabdomyolysis 20.31 15.56 44 6583 63536 29882315
Insomnia 19.62 15.56 55 6572 93281 29852570
Liver disorder 19.18 15.56 28 6599 29694 29916157
Alanine aminotransferase increased 17.85 15.56 46 6581 74230 29871621
Hyporesponsive to stimuli 17.67 15.56 7 6620 955 29944896
Delirium 17.66 15.56 32 6595 40599 29905252
Decreased appetite 16.32 15.56 71 6556 149839 29796012
Aspartate aminotransferase increased 15.98 15.56 40 6587 63382 29882469
Disseminated intravascular coagulation 15.94 15.56 22 6605 22149 29923702
Amnesia 15.82 15.56 23 6604 24298 29921553
Disinhibition 15.77 15.56 8 6619 1949 29943902
Urinary incontinence 15.61 15.56 19 6608 16921 29928930

Pharmacologic Action:

SourceCodeDescription
ATC N05CD05 NERVOUS SYSTEM
PSYCHOLEPTICS
HYPNOTICS AND SEDATIVES
Benzodiazepine derivatives
FDA CS M0002356 Benzodiazepines
MeSH PA D000759 Adjuvants, Anesthesia
MeSH PA D014151 Anti-Anxiety Agents
MeSH PA D002491 Central Nervous System Agents
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D018682 GABA Agents
MeSH PA D018757 GABA Modulators
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D011619 Psychotropic Drugs
MeSH PA D014149 Tranquilizing Agents
FDA EPC N0000175694 Benzodiazepine

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Insomnia indication 193462001
Suicidal thoughts contraindication 6471006
Alcohol intoxication contraindication 25702006
Depressive disorder contraindication 35489007
Substance abuse contraindication 66214007
Psychotic disorder contraindication 69322001
Sleep apnea contraindication 73430006 DOID:0050847
Kidney disease contraindication 90708001 DOID:557
Myasthenia gravis contraindication 91637004 DOID:437
Hypoalbuminemia contraindication 119247004
Disease of liver contraindication 235856003 DOID:409
Sleep automatism contraindication 247962006
Syncope contraindication 271594007
Pregnancy, function contraindication 289908002
Breastfeeding (mother) contraindication 413712001
Chronic lung disease contraindication 413839001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 5.22 Basic
pKa2 4.62 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-5/beta-3/gamma-3 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 8.70 WOMBAT-PK CHEMBL
GABA-A receptor alpha-1/beta-2/gamma-3 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 8.64 WOMBAT-PK CHEMBL
GABA A receptor alpha-5/beta-2/gamma-2 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 9.22 WOMBAT-PK CHEMBL
GABA A receptor alpha-5/beta-2/gamma-3 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 8.70 WOMBAT-PK CHEMBL
GABA-A receptor Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 9.10 IUPHAR CHEMBL
GABA-A receptor alpha-5/beta-3/gamma-2 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 9.02 WOMBAT-PK CHEMBL
GABA-A receptor alpha-1/beta-2/gamma-2 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 9.15 WOMBAT-PK CHEMBL
GABA-A receptor alpha-1/beta-3/gamma-2 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 9.10 WOMBAT-PK CHEMBL
GABA-A receptor alpha-2/beta-3/gamma-2 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 9.23 WOMBAT-PK CHEMBL
GABA A receptor alpha-3/beta-2/gamma-2 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 8.88 WOMBAT-PK CHEMBL
GABA-A receptor alpha-3/beta-3/gamma-2 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 8.84 WOMBAT-PK CHEMBL
GABA A receptor alpha-3/beta-2/gamma-3 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 8.11 WOMBAT-PK CHEMBL
Cytochrome P450 3A4 Enzyme Ki 4.27 WOMBAT-PK
Platelet-activating factor receptor GPCR Ki 5.88 PDSP
GABA-A receptor; anion channel Ion channel Ki 9.10 CHEMBL
Cholecystokinin receptor type A GPCR IC50 4.41 CHEMBL

External reference:

IDSource
4018066 VUID
N0000146407 NUI
D00387 KEGG_DRUG
4018066 VANDF
C0040879 UMLSCUI
CHEMBL646 ChEMBL_ID
D014229 MESH_DESCRIPTOR_UI
3409 INN_ID
DB00897 DRUGBANK_ID
1HM943223R UNII
5556 PUBCHEM_CID
7313 IUPHAR_LIGAND_ID
10767 RXNORM
3103 MMSL
5618 MMSL
d00397 MMSL
001466 NDDF
111128007 SNOMEDCT_US
386984001 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Halcion HUMAN PRESCRIPTION DRUG LABEL 1 0009-0017 TABLET 0.25 mg ORAL NDA 33 sections
Triazolam HUMAN PRESCRIPTION DRUG LABEL 1 0054-4858 TABLET 0.13 mg ORAL ANDA 30 sections
Triazolam HUMAN PRESCRIPTION DRUG LABEL 1 0054-4859 TABLET 0.25 mg ORAL ANDA 30 sections
TRIAZOLAM HUMAN PRESCRIPTION DRUG LABEL 1 16590-236 TABLET 0.25 mg ORAL NDA authorized generic 28 sections
Triazolam HUMAN PRESCRIPTION DRUG LABEL 1 21695-284 TABLET 0.25 mg ORAL ANDA 22 sections
Triazolam HUMAN PRESCRIPTION DRUG LABEL 1 21695-303 TABLET 0.13 mg ORAL ANDA 22 sections
Triazolam HUMAN PRESCRIPTION DRUG LABEL 1 43063-996 TABLET 0.25 mg ORAL ANDA 29 sections
Triazolam HUMAN PRESCRIPTION DRUG LABEL 1 43353-451 TABLET 0.25 mg ORAL NDA AUTHORIZED GENERIC 29 sections
Triazolam HUMAN PRESCRIPTION DRUG LABEL 1 50090-0522 TABLET 0.25 mg ORAL NDA AUTHORIZED GENERIC 32 sections
Triazolam HUMAN PRESCRIPTION DRUG LABEL 1 50090-4733 TABLET 0.25 mg ORAL ANDA 30 sections
Triazolam HUMAN PRESCRIPTION DRUG LABEL 1 50436-3718 TABLET 0.25 mg ORAL NDA AUTHORIZED GENERIC 28 sections
Triazolam HUMAN PRESCRIPTION DRUG LABEL 1 50742-645 TABLET 0.13 mg ORAL ANDA 29 sections
Triazolam HUMAN PRESCRIPTION DRUG LABEL 1 50742-646 TABLET 0.25 mg ORAL ANDA 29 sections
Triazolam HUMAN PRESCRIPTION DRUG LABEL 1 55289-787 TABLET 0.25 mg ORAL NDA authorized generic 32 sections
Triazolam HUMAN PRESCRIPTION DRUG LABEL 1 59762-3717 TABLET 0.13 mg ORAL NDA AUTHORIZED GENERIC 33 sections
Triazolam HUMAN PRESCRIPTION DRUG LABEL 1 59762-3718 TABLET 0.25 mg ORAL NDA AUTHORIZED GENERIC 33 sections
Triazolam HUMAN PRESCRIPTION DRUG LABEL 1 63629-2956 TABLET 0.25 mg ORAL ANDA 29 sections
Triazolam HUMAN PRESCRIPTION DRUG LABEL 1 67544-725 TABLET 0.25 mg ORAL ANDA 23 sections