rosiglitazone ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
peroxisome proliferator activating receptor-gamma (PPAR-gamma) agonists, thiazolidinedione derivatives 2405 122320-73-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • rosiglitazone
  • rosiglitazone maleate
  • rosiglizole
  • rosiglitazone hydrochloride
  • rosiglitazone HCl
A thiazolidinedione that functions as a selective agonist for PPAR GAMMA. It improves INSULIN SENSITIVITY in adipose tissue, skeletal muscle, and the liver of patients with TYPE 2 DIABETES MELLITUS.
  • Molecular weight: 357.43
  • Formula: C18H19N3O3S
  • CLOGP: 3.02
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 1
  • TPSA: 71.53
  • ALOGS: -3.97
  • ROTB: 7

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
6 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.04 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.37 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 99 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.20 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.65 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.00 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 3.90 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
May 25, 1999 FDA SB PHARMCO

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
Cardiac failure congestive 16777.07 162.76 4181 14733 80201 50506009
Myocardial infarction 13616.55 162.76 3592 15322 85435 50500775
Coronary artery disease 6104.37 162.76 1535 17379 28191 50558019
Cerebrovascular accident 5758.01 162.76 1890 17024 92790 50493420
Acute myocardial infarction 2752.64 162.76 821 18093 28452 50557758
Coronary arterial stent insertion 1704.09 162.76 349 18565 2285 50583925
Coronary artery bypass 1165.76 162.76 249 18665 2044 50584166
Angina unstable 983.83 162.76 267 18647 6439 50579771
Myocardial ischaemia 761.19 162.76 248 18666 11365 50574845
Vascular graft 508.99 162.76 104 18810 667 50585543
Transient ischaemic attack 500.66 162.76 243 18671 31967 50554243
Angina pectoris 494.53 162.76 226 18688 25962 50560248
Chest pain 441.02 162.76 428 18486 176454 50409756
Cardio-respiratory arrest 403.74 162.76 251 18663 53641 50532569
Arteriosclerosis 373.55 162.76 137 18777 8940 50577270
Acute coronary syndrome 361.91 162.76 135 18779 9239 50576971
Cardiomyopathy 321.01 162.76 143 18771 15443 50570767
Atrial fibrillation 318.60 162.76 280 18634 101465 50484745
Arteriosclerosis coronary artery 316.96 162.76 116 18798 7520 50578690
Sudden cardiac death 314.74 162.76 84 18830 1888 50584322
Ischaemic cardiomyopathy 301.50 162.76 84 18830 2228 50583982
Drug ineffective 275.18 162.76 7 18907 819326 49766884
Cardiac arrest 225.92 162.76 212 18702 83439 50502771
Nausea 219.41 162.76 11 18903 705387 49880823
Cardiac disorder 212.94 162.76 155 18759 42824 50543386
Fatigue 194.43 162.76 20 18894 707581 49878629
Diarrhoea 186.63 162.76 8 18906 588468 49997742

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
Myocardial infarction 18392.09 267.15 5710 19982 104586 29444249
Cardiac failure congestive 14154.29 267.15 4321 21371 72260 29476575
Coronary artery disease 9043.85 267.15 2718 22974 41472 29507363
Cerebrovascular accident 5297.09 267.15 2102 23590 74809 29474026
Acute myocardial infarction 3507.11 267.15 1378 24314 47060 29501775
Coronary artery bypass 2659.93 267.15 650 25042 4035 29544800
Coronary arterial stent insertion 2600.27 267.15 616 25076 3281 29545554
Angina unstable 1156.41 267.15 412 25280 10453 29538382
Myocardial ischaemia 836.98 267.15 363 25329 15665 29533170
Vascular graft 794.71 267.15 194 25498 1186 29547649
Ischaemic cardiomyopathy 622.86 267.15 220 25472 5418 29543417
Arteriosclerosis coronary artery 529.89 267.15 233 25459 10372 29538463
Angina pectoris 483.52 267.15 301 25391 27549 29521286
Transient ischaemic attack 474.84 267.15 279 25413 22991 29525844
Acute coronary syndrome 432.46 267.15 212 25480 12113 29536722
Arteriosclerosis 422.53 267.15 197 25495 10059 29538776
Cardiomyopathy 327.24 267.15 187 25505 14600 29534235
Cardio-respiratory arrest 327.21 267.15 303 25389 50298 29498537
Sudden cardiac death 296.86 267.15 110 25582 3112 29545723
Atrial fibrillation 288.44 267.15 404 25288 105242 29443593

FDA Adverse Event Reporting System (Geriatric)

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
Myocardial infarction 30002.82 293.15 8330 28724 157491 64304187
Cardiac failure congestive 27922.76 293.15 7502 29552 123078 64338600
Coronary artery disease 11949.90 293.15 3308 33746 57125 64404553
Cerebrovascular accident 10619.64 293.15 3656 33398 133927 64327751
Acute myocardial infarction 6197.15 293.15 2071 34983 67647 64394031
Coronary arterial stent insertion 4379.58 293.15 937 36117 4755 64456923
Coronary artery bypass 3832.39 293.15 843 36211 4972 64456706
Angina unstable 1856.89 293.15 580 36474 14887 64446791
Vascular graft 1292.61 293.15 282 36772 1577 64460101
Myocardial ischaemia 1248.34 293.15 478 36576 22773 64438905
Angina pectoris 837.40 293.15 441 36613 44640 64417038
Transient ischaemic attack 777.66 293.15 417 36637 43765 64417913
Arteriosclerosis 661.55 293.15 272 36782 15605 64446073
Cardio-respiratory arrest 642.58 293.15 497 36557 97896 64363782
Acute coronary syndrome 642.51 293.15 282 36772 19028 64442650
Chest pain 630.90 293.15 725 36329 235255 64226423
Sudden cardiac death 520.60 293.15 165 36889 4422 64457256
Arteriosclerosis coronary artery 497.88 293.15 221 36833 15308 64446370
Ischaemic cardiomyopathy 486.13 293.15 173 36881 6665 64455013
Drug ineffective 453.48 293.15 6 37048 840241 63621437
Nausea 409.86 293.15 9 37045 785791 63675887
Cardiomyopathy 386.98 293.15 218 36836 25138 64436540
Diarrhoea 373.95 293.15 9 37045 722695 63738983
Fatigue 367.14 293.15 15 37039 748715 63712963
Cardiac arrest 359.03 293.15 442 36612 153622 64308056
Atrial fibrillation 349.99 293.15 460 36594 170629 64291049
Dyspnoea 298.46 293.15 33 37021 718641 63743037
Pyrexia 296.48 293.15 5 37049 558639 63903039
Vomiting 296.45 293.15 4 37050 551113 63910565

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC A10BD03 ALIMENTARY TRACT AND METABOLISM
DRUGS USED IN DIABETES
BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
Combinations of oral blood glucose lowering drugs
ATC A10BD04 ALIMENTARY TRACT AND METABOLISM
DRUGS USED IN DIABETES
BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
Combinations of oral blood glucose lowering drugs
ATC A10BG02 ALIMENTARY TRACT AND METABOLISM
DRUGS USED IN DIABETES
BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
Thiazolidinediones
FDA CS M0199114 PPAR gamma
FDA CS M0447306 Thiazolidinediones
FDA MoA N0000175374 Peroxisome Proliferator-activated Receptor Activity
MeSH PA D007004 Hypoglycemic Agents
FDA EPC N0000180186 Peroxisome Proliferator Receptor gamma Agonist
FDA EPC N0000180190 Thiazolidinedione
CHEBI has role CHEBI:50864 insulin sensitizers
CHEBI has role CHEBI:83157 EC 6.2.1.3 inhibitors
CHEBI has role CHEBI:173084 ferroptosis inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Treatment Refractory Type 2 Diabetes Mellitus indication
Alcoholism contraindication 7200002
Weight gain finding contraindication 8943002
Asthenia contraindication 13791008
Pulmonary edema contraindication 19242006 DOID:11396
Myocardial infarction contraindication 22298006 DOID:5844
Acute vomiting contraindication 23971007
Alcohol intoxication contraindication 25702006
Shock contraindication 27942005
Dehydration contraindication 34095006
Macular retinal edema contraindication 37231002 DOID:4449
Infectious disease contraindication 40733004
Body fluid retention contraindication 43498006
Chronic heart failure contraindication 48447003
Hepatic porphyria contraindication 55056006 DOID:3133
Ketoacidosis contraindication 56051008
Metabolic acidosis contraindication 59455009
Hemolytic anemia contraindication 61261009 DOID:583
Glucose-6-phosphate dehydrogenase deficiency anemia contraindication 62403005
Osteoporosis contraindication 64859006 DOID:11476
Hypopituitarism contraindication 74728003 DOID:9406
Cardiogenic shock contraindication 89138009
Kidney disease contraindication 90708001 DOID:557
Lactic acidosis contraindication 91273001 DOID:3650
Fracture of bone contraindication 125605004
Autonomic dysreflexia contraindication 129618003
Liver function tests abnormal contraindication 166603001
Cobalamin deficiency contraindication 190634004
Angina pectoris contraindication 194828000
Decompensated cardiac failure contraindication 195111005
Cerebrovascular accident contraindication 230690007
Disease of liver contraindication 235856003 DOID:409
Drug-induced hepatitis contraindication 235876009
Hypoglycemic disorder contraindication 237630007
Sepsis syndrome contraindication 238150007
Osteopenia contraindication 312894000
Primary adrenocortical insufficiency contraindication 373662000
Adrenal cortical hypofunction contraindication 386584007 DOID:10493
Fever contraindication 386661006
Surgical procedure contraindication 387713003
Severe diarrhea contraindication 409587002
Breastfeeding (mother) contraindication 413712001
Disorder of coronary artery contraindication 414024009
Myocardial ischemia contraindication 414795007 DOID:3393
Traumatic injury contraindication 417746004
Fever greater than 100.4 Fahrenheit contraindication 426000000
Radiography with IV Iodinated Contrast Agent contraindication
Severe Hypoxemia contraindication




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 6.5 acidic
pKa2 5.84 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
Peroxisome proliferator-activated receptor gamma Nuclear hormone receptor AGONIST EC50 7.04 WOMBAT-PK CHEMBL
Carbonic anhydrase 2 Enzyme IC50 5.39 DRUG MATRIX
Bile salt export pump Transporter IC50 5.19 CHEMBL
Amine oxidase [flavin-containing] B Enzyme Ki 5.38 CHEMBL
Amine oxidase [flavin-containing] A Enzyme Ki 4.56 CHEMBL
Peroxisome proliferator-activated receptor alpha Nuclear hormone receptor EC50 7.41 CHEMBL
Retinoic acid receptor RXR-alpha Nuclear hormone receptor Kd 4.82 CHEMBL
Retinoic acid receptor gamma Nuclear hormone receptor Ki 5 CHEMBL
Thromboxane-A synthase Enzyme IC50 5.45 DRUG MATRIX
Peroxisome proliferator-activated receptor delta Nuclear hormone receptor EC50 5.44 CHEMBL
Free fatty acid receptor 1 GPCR AGONIST EC50 5.60 IUPHAR
Short transient receptor potential channel 5 Ion channel ACTIVATOR EC50 4.51 IUPHAR
Sodium/bile acid cotransporter Transporter IC50 5.29 CHEMBL
CDGSH iron-sulfur domain-containing protein 1 Unclassified Ki 7.51 CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 4.53 CHEMBL
CDGSH iron-sulfur domain-containing protein 2 Unclassified IC50 5.64 CHEMBL
Amine oxidase [flavin-containing] B Enzyme Ki 5.24 CHEMBL
Amine oxidase [flavin-containing] A Enzyme Ki 4.49 CHEMBL
Peroxisome proliferator-activated receptor alpha Transcription factor IC50 7.10 CHEMBL
Peroxisome proliferator-activated receptor gamma Transcription factor EC50 7.52 CHEMBL
Type-1A angiotensin II receptor GPCR Ki 9.64 CHEMBL
Bile salt export pump Transporter IC50 4.40 CHEMBL
CDGSH iron-sulfur domain-containing protein 1 Unclassified IC50 5.96 CHEMBL

External reference:

IDSource
4021162 VUID
N0000148613 NUI
D00596 KEGG_DRUG
155141-29-0 SECONDARY_CAS_RN
4021162 VANDF
4021163 VANDF
C0289313 UMLSCUI
CHEBI:50122 CHEBI
BRL PDB_CHEM_ID
CHEMBL121 ChEMBL_ID
DB00412 DRUGBANK_ID
CHEMBL843 ChEMBL_ID
D000077154 MESH_DESCRIPTOR_UI
77999 PUBCHEM_CID
1056 IUPHAR_LIGAND_ID
7662 INN_ID
302543-62-0 SECONDARY_CAS_RN
05V02F2KDG UNII
253198 RXNORM
8221 MMSL
d04434 MMSL
007789 NDDF
007790 NDDF
116096001 SNOMEDCT_US
326053005 SNOMEDCT_US
395869000 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Avandia HUMAN PRESCRIPTION DRUG LABEL 1 54868-4198 TABLET, FILM COATED 4 mg ORAL NDA 19 sections
Avandia HUMAN PRESCRIPTION DRUG LABEL 1 54868-4221 TABLET, FILM COATED 8 mg ORAL NDA 19 sections
AVANDAMET HUMAN PRESCRIPTION DRUG LABEL 2 54868-4965 TABLET, FILM COATED 2 mg ORAL NDA 30 sections
AVANDAMET HUMAN PRESCRIPTION DRUG LABEL 2 54868-5157 TABLET, FILM COATED 4 mg ORAL NDA 30 sections
Avandia HUMAN PRESCRIPTION DRUG LABEL 1 54868-5249 TABLET, FILM COATED 2 mg ORAL NDA 19 sections
AVANDAMET HUMAN PRESCRIPTION DRUG LABEL 2 54868-5262 TABLET, FILM COATED 4 mg ORAL NDA 30 sections
AVANDAMET HUMAN PRESCRIPTION DRUG LABEL 2 54868-5376 TABLET, FILM COATED 2 mg ORAL NDA 30 sections