rosiglitazone 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 ┬ÁM/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 34199.67 181.86 6483 9874 9618 2332110
Myocardial infarction 29161.75 181.86 5854 10503 13159 2328569
Cerebrovascular accident 12473.49 181.86 3005 13352 17181 2324547
Coronary artery disease 12263.98 181.86 2394 13963 3545 2338183
Acute myocardial infarction 4551.72 181.86 1034 15323 4021 2337707
Cardiac disorder 2199.51 181.86 634 15723 7199 2334529
Myocardial ischaemia 2187.55 181.86 492 15865 1770 2339958
Coronary arterial stent insertion 2105.13 181.86 387 15970 268 2341460
Angina unstable 2017.14 181.86 421 15936 945 2340783
Transient ischaemic attack 1958.01 181.86 546 15811 5432 2336296
Coronary artery bypass 1946.42 181.86 358 15999 249 2341479
Chest pain 1539.92 181.86 675 15682 27462 2314266
Atrial fibrillation 1505.95 181.86 545 15812 13223 2328505
Cardiovascular disorder 1477.98 181.86 361 15996 1994 2339734
Angina pectoris 1437.17 181.86 393 15964 3594 2338134
Acute coronary syndrome 1082.49 181.86 260 16097 1317 2340411
Ischaemic cardiomyopathy 1006.54 181.86 198 16159 278 2341450
Cardiomyopathy 952.12 181.86 264 16093 2543 2339185
Cardio-respiratory arrest 935.03 181.86 345 16012 8801 2332927
Arteriosclerosis 927.35 181.86 227 16130 1261 2340467
Cardiac arrest 888.62 181.86 381 15976 14549 2327179
Heart injury 846.53 181.86 159 16198 141 2341587
Hypertension 799.23 181.86 428 15929 26933 2314795
Arteriosclerosis coronary artery 736.13 181.86 180 16177 993 2340735
Vascular graft 651.31 181.86 125 16232 139 2341589
Stent placement 603.61 181.86 140 16217 589 2341139
Cardiac failure 467.72 181.86 229 16128 11865 2329863
Pulmonary oedema 467.41 181.86 197 16160 7166 2334562
Sudden cardiac death 443.84 181.86 103 16254 434 2341294
Arrhythmia 435.76 181.86 177 16180 5851 2335877
Pleural effusion 380.79 181.86 197 16160 11471 2330257
Congestive cardiomyopathy 328.14 181.86 91 16266 872 2340856
Coronary artery occlusion 269.82 181.86 83 16274 1175 2340553
Hypertensive heart disease 265.54 181.86 65 16292 359 2341369
Supraventricular tachycardia 258.36 181.86 90 16267 1919 2339809
Cerebral infarction 252.64 181.86 110 16247 4327 2337401
Cardiogenic shock 239.47 181.86 90 16267 2401 2339327
Mitral valve incompetence 233.81 181.86 89 16268 2461 2339267
Death 232.08 181.86 334 16023 81134 2260594
Injury 221.74 181.86 110 16247 5844 2335884
Cardiomegaly 217.43 181.86 83 16274 2313 2339415
Oedema 214.23 181.86 129 16228 10074 2331654
Weight increased 206.73 181.86 171 16186 22166 2319562
Renal failure 199.60 181.86 151 16206 17198 2324530
Dyspnoea 191.54 181.86 300 16057 78433 2263295
Ventricular tachycardia 189.01 181.86 80 16277 2931 2338797
Sinus node dysfunction 188.70 181.86 55 16302 639 2341089
Pericardial effusion 185.53 181.86 86 16271 3923 2337805
Aortic stenosis 183.81 181.86 53 16304 591 2341137
Catheterisation cardiac 183.15 181.86 54 16303 655 2341073

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 42677.83 205.22 9795 12969 17379 1706638
Cardiac failure congestive 32461.56 205.22 7150 15614 8120 1715897
Coronary artery disease 19546.44 205.22 4417 18347 5429 1718588
Cerebrovascular accident 12873.46 205.22 3574 19190 14292 1709725
Acute myocardial infarction 6496.83 205.22 1801 20963 6786 1717231
Coronary artery bypass 4414.42 205.22 930 21834 452 1723565
Cardiac disorder 3283.12 205.22 1040 21724 6651 1717366
Coronary arterial stent insertion 3265.35 205.22 685 22079 307 1723710
Myocardial ischaemia 3037.52 205.22 806 21958 2387 1721630
Angina unstable 2526.72 205.22 643 22121 1515 1722502
Ischaemic cardiomyopathy 2414.93 205.22 549 22215 598 1723419
Cardiovascular disorder 2084.23 205.22 572 22192 1985 1722032
Atrial fibrillation 2031.97 205.22 874 21890 14237 1709780
Transient ischaemic attack 1867.51 205.22 606 22158 4185 1719832
Angina pectoris 1656.33 205.22 560 22204 4458 1719559
Acute coronary syndrome 1360.17 205.22 403 22361 1952 1722065
Cardiomyopathy 1340.53 205.22 413 22351 2339 1721678
Arteriosclerosis coronary artery 1306.34 205.22 372 22392 1520 1722497
Arteriosclerosis 1297.09 205.22 368 22396 1479 1722538
Cardiac arrest 1294.37 205.22 651 22113 15279 1708738
Chest pain 1201.39 205.22 667 22097 19247 1704770
Stent placement 1118.31 205.22 287 22477 701 1723316
Vascular graft 1066.08 205.22 237 22527 208 1723809
Cardio-respiratory arrest 1031.37 205.22 471 22293 8822 1715195
Heart injury 986.10 205.22 216 22548 163 1723854
Hypertension 712.72 205.22 474 22290 18974 1705043
Arrhythmia 623.16 205.22 291 22473 5725 1718292
Sudden cardiac death 584.42 205.22 167 22597 689 1723328
Coronary artery occlusion 570.05 205.22 202 22562 1861 1722156
Cardiac failure 436.54 205.22 297 22467 12305 1711712
Congestive cardiomyopathy 388.76 205.22 132 22632 1055 1722962
Pulmonary oedema 380.21 205.22 215 22549 6371 1717646
Pleural effusion 370.85 205.22 256 22508 10854 1713163
Macular oedema 344.70 205.22 110 22654 706 1723311
Injury 333.76 205.22 152 22612 2808 1721209
Catheterisation cardiac 331.64 205.22 93 22671 352 1723665
Implantable defibrillator insertion 316.07 205.22 76 22688 124 1723893
Ventricular tachycardia 312.32 205.22 157 22607 3641 1720376
Ischaemia 287.39 205.22 98 22666 794 1723223
Cardiogenic shock 251.61 205.22 118 22646 2336 1721681
Cerebral infarction 247.60 205.22 150 22614 5059 1718958
Atrial flutter 242.08 205.22 107 22657 1835 1722182
Carotid artery stenosis 230.54 205.22 81 22683 724 1723293
Aortic stenosis 227.46 205.22 75 22689 541 1723476
Sinus node dysfunction 226.51 205.22 77 22687 617 1723400
Hyperlipidaemia 224.88 205.22 106 22658 2123 1721894
Mitral valve incompetence 222.90 205.22 101 22663 1841 1722176
Hypertensive heart disease 222.83 205.22 69 22695 395 1723622
Lacunar infarction 222.19 205.22 73 22691 520 1723497
Silent myocardial infarction 216.17 205.22 52 22712 85 1723932
Cardiac pacemaker insertion 214.97 205.22 70 22694 483 1723534
Supraventricular tachycardia 214.95 205.22 94 22670 1569 1722448
Peripheral vascular disorder 208.45 205.22 75 22689 723 1723294

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 EPC N0000180186 Peroxisome Proliferator Receptor gamma Agonist
FDA MoA N0000175374 Peroxisome Proliferator-activated Receptor Activity
FDA CS M0199114 PPAR gamma
FDA EPC N0000180190 Thiazolidinedione
FDA CS M0447306 Thiazolidinediones
MeSH PA D007004 Hypoglycemic Agents
CHEBI has role CHEBI:50864 insulin-sensitizing drug

Drug Use (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

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
Free fatty acid receptor 1 GPCR AGONIST EC50 5.60 IUPHAR
Carbonic anhydrase 2 Enzyme IC50 5.39 DRUG MATRIX
Thromboxane-A synthase Enzyme IC50 5.45 DRUG MATRIX
Amine oxidase [flavin-containing] A Enzyme Ki 4.56 CHEMBL
Peroxisome proliferator-activated receptor delta Nuclear hormone receptor EC50 5.44 CHEMBL
Amine oxidase [flavin-containing] B Enzyme Ki 5.38 CHEMBL
Peroxisome proliferator-activated receptor alpha Nuclear hormone receptor EC50 7.41 CHEMBL
Retinoic acid receptor gamma Nuclear hormone receptor Ki 5 CHEMBL
Short transient receptor potential channel 5 Ion channel ACTIVATOR EC50 4.51 IUPHAR
Bile salt export pump Transporter IC50 5.19 CHEMBL
Type-1A angiotensin II receptor GPCR Ki 9.64 CHEMBL
Amine oxidase [flavin-containing] B Enzyme Ki 5.24 CHEMBL
Amine oxidase [flavin-containing] A Enzyme Ki 4.49 CHEMBL
Bile salt export pump Unclassified IC50 4.40 CHEMBL
Peroxisome proliferator-activated receptor gamma Transcription factor EC50 7.52 CHEMBL

External reference:

IDSource
D000077154 MESH_DESCRIPTOR_UI
4021162 VUID
N0000148613 NUI
C0289313 UMLSCUI
D00596 KEGG_DRUG
05V02F2KDG UNII
7662 INN_ID
326053005 SNOMEDCT_US
d04434 MMSL
84108 RXNORM
4021162 VANDF
395869000 SNOMEDCT_US
007789 NDDF
CHEMBL121 ChEMBL_ID
CHEMBL843 ChEMBL_ID
DB00412 DRUGBANK_ID
155141-29-0 SECONDARY_CAS_RN
BRL PDB_CHEM_ID
CHEBI:50122 CHEBI
77999 PUBCHEM_CID
1056 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
AVANDIA HUMAN PRESCRIPTION DRUG LABEL 1 0173-0861 TABLET, FILM COATED 2 mg ORAL NDA 20 sections
AVANDIA HUMAN PRESCRIPTION DRUG LABEL 1 0173-0863 TABLET, FILM COATED 4 mg ORAL NDA 20 sections
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 21 sections
AVANDAMET HUMAN PRESCRIPTION DRUG LABEL 2 54868-5157 TABLET, FILM COATED 4 mg ORAL NDA 21 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 21 sections
AVANDAMET HUMAN PRESCRIPTION DRUG LABEL 2 54868-5376 TABLET, FILM COATED 2 mg ORAL NDA 21 sections