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

Stem definitionDrug idCAS RN
peroxisome proliferator activating receptor-gamma (PPAR-gamma) agonists, thiazolidinedione derivatives 2179 111025-46-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • pioglitazone
  • glustin
  • sepioglin
  • pioglitazone hydrochloride
  • pioglitazone HCl
Pioglitazone is a thiazolidinedione that depends on the presence of insulin for its mechanism of action. Pioglitazone decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. Pioglitazone is not an insulin secretagogue. Pioglitazone is an agonist for peroxisome proliferator-activated receptor-gamma (PPAR-gamma). PPAR receptors are found in tissues important for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPAR-gamma nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism.
  • Molecular weight: 356.44
  • Formula: C19H20N2O3S
  • CLOGP: 3.53
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 1
  • TPSA: 68.29
  • ALOGS: -4.91
  • ROTB: 7

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
30 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 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) 1.80 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 83 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

DateAgencyCompanyOrphan
July 15, 1999 FDA TAKEDA PHARMS USA

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
Bladder cancer 954.44 33.71 143 1499 581 2355862
Hypoglycaemia 425.19 33.71 108 1534 8299 2348144
Weight increased 402.51 33.71 128 1514 22209 2334234
Cardiac failure congestive 338.53 33.71 104 1538 15997 2340446
Oedema peripheral 334.10 33.71 113 1529 23650 2332793
Dyspnoea 237.58 33.71 125 1517 78608 2277835
Blood glucose increased 210.23 33.71 68 1574 12222 2344221
Cardiac failure 194.99 33.71 64 1578 12030 2344413
Drug hypersensitivity 165.72 33.71 83 1559 46560 2309883
Oedema 164.36 33.71 54 1588 10149 2346294
Diabetic metabolic decompensation 157.84 33.71 25 1617 150 2356293
Fall 156.13 33.71 80 1562 47019 2309424
Diabetes mellitus inadequate control 155.08 33.71 36 1606 1851 2354592
Bladder transitional cell carcinoma 116.71 33.71 18 1624 88 2356355
Lactic acidosis 113.76 33.71 35 1607 5295 2351148
Blood glucose decreased 102.97 33.71 29 1613 3223 2353220
Glycosylated haemoglobin increased 94.31 33.71 24 1618 1810 2354633
Fluid retention 92.39 33.71 32 1610 7014 2349429
Macular oedema 92.33 33.71 21 1621 981 2355462
Chest pain 79.20 33.71 43 1599 28094 2328349
Dyspnoea exertional 78.93 33.71 27 1615 5693 2350750
Haematuria 78.08 33.71 25 1617 4293 2352150
Dizziness 72.14 33.71 53 1589 58612 2297831
Tibia fracture 69.52 33.71 16 1626 787 2355656
Hyperglycaemia 67.15 33.71 23 1619 4862 2351581
Bladder neoplasm 62.37 33.71 11 1631 135 2356308
Suicide attempt 61.12 33.71 27 1615 11255 2345188
Condition aggravated 61.05 33.71 38 1604 31941 2324502
Pleural effusion 60.25 33.71 27 1615 11641 2344802
Shock 59.54 33.71 20 1622 3984 2352459
Asthenia 54.46 33.71 41 1601 46885 2309558
Renal impairment 54.16 33.71 24 1618 10068 2346375
Acute kidney injury 52.59 33.71 33 1609 28089 2328354
Ureteric cancer 50.91 33.71 8 1634 45 2356398
Myocardial infarction 50.49 33.71 28 1614 18985 2337458
Malaise 48.33 33.71 41 1601 55544 2300899
Cardiomegaly 47.96 33.71 15 1627 2381 2354062
Nausea 47.72 33.71 56 1586 112133 2244310
Hypoglycaemic coma 47.50 33.71 11 1631 555 2355888
Abdominal pain 46.55 33.71 33 1609 34341 2322102
Anaemia 46.19 33.71 33 1609 34759 2321684
Vomiting 44.98 33.71 44 1598 71558 2284885
Weight decreased 44.93 33.71 30 1612 28341 2328102
Incorrect dose administered 42.39 33.71 20 1622 9675 2346768
Diabetic retinopathy 41.42 33.71 9 1633 339 2356104
Urinary tract infection 41.11 33.71 29 1613 29913 2326530
Pulmonary oedema 41.07 33.71 18 1624 7345 2349098
Tachypnoea 40.65 33.71 13 1629 2216 2354227
Intentional overdose 39.44 33.71 20 1622 11301 2345142
Treatment noncompliance 39.08 33.71 16 1626 5518 2350925
Product dispensing error 38.98 33.71 13 1629 2528 2353915
Fatigue 38.74 33.71 44 1598 84829 2271614
Medication error 37.50 33.71 16 1626 6115 2350328
Headache 37.32 33.71 42 1600 80137 2276306
Pain 35.09 33.71 36 1606 61821 2294622
Tachycardia 35.08 33.71 21 1621 16388 2340055
Acute pulmonary oedema 34.27 33.71 10 1632 1253 2355190
Respiratory arrest 34.11 33.71 15 1627 6163 2350280

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
Bladder cancer 4254.20 38.44 667 1773 1389 1742952
Bladder transitional cell carcinoma 760.67 38.44 123 2317 283 1744058
Haematuria 347.64 38.44 110 2330 7450 1736891
Oedema peripheral 333.60 38.44 128 2312 15422 1728919
Cardiac failure congestive 328.63 38.44 126 2314 15144 1729197
Hypoglycaemia 272.11 38.44 94 2346 8344 1735997
Weight increased 209.46 38.44 84 2356 11273 1733068
Blood glucose increased 156.77 38.44 67 2373 10517 1733824
Dyspnoea 152.19 38.44 113 2327 51946 1692395
Cardiac failure 151.85 38.44 69 2371 12533 1731808
Oedema 136.93 38.44 54 2386 6894 1737447
Transitional cell carcinoma 121.06 38.44 25 2415 285 1744056
Bladder neoplasm 114.48 38.44 24 2416 296 1744045
Macular oedema 111.79 38.44 28 2412 788 1743553
Diabetes mellitus inadequate control 106.22 38.44 32 2408 1810 1742531
Prostate cancer 91.21 38.44 36 2404 4590 1739751
Pulmonary oedema 88.54 38.44 39 2401 6547 1737794
Completed suicide 74.86 38.44 47 2393 16265 1728076
Myocardial infarction 70.12 38.44 55 2385 27119 1717222
Glycosylated haemoglobin increased 64.30 38.44 22 2418 1869 1742472
Ureteric cancer 61.37 38.44 11 2429 54 1744287
Bladder cancer recurrent 61.16 38.44 12 2428 103 1744238
Condition aggravated 57.09 38.44 44 2396 21106 1723235
Blood glucose decreased 52.55 38.44 20 2420 2305 1742036
Drug hypersensitivity 50.98 38.44 36 2404 15099 1729242
Fall 49.36 38.44 45 2395 27169 1717172
Pleural effusion 48.37 38.44 31 2409 11079 1733262
Fluid retention 46.16 38.44 21 2419 3788 1740553
Cardiomegaly 45.38 38.44 18 2422 2316 1742025
Anaemia 44.44 38.44 44 2396 29413 1714928
Diabetic retinopathy 43.20 38.44 11 2429 330 1744011
Pollakiuria 41.33 38.44 18 2422 2928 1741413
Dysuria 40.61 38.44 19 2421 3653 1740688
Loss of consciousness 40.20 38.44 31 2409 14844 1729497
Chest pain 40.18 38.44 35 2405 19879 1724462
Pancreatic carcinoma 39.52 38.44 15 2425 1714 1742627
Renal cyst 38.89 38.44 13 2427 1027 1743314

Pharmacologic Action:

SourceCodeDescription
ATC A10BG03 ALIMENTARY TRACT AND METABOLISM
DRUGS USED IN DIABETES
BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
Thiazolidinediones
ATC A10BD05 ALIMENTARY TRACT AND METABOLISM
DRUGS USED IN DIABETES
BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
Combinations of oral blood glucose lowering drugs
ATC A10BD06 ALIMENTARY TRACT AND METABOLISM
DRUGS USED IN DIABETES
BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
Combinations of oral blood glucose lowering drugs
ATC A10BD09 ALIMENTARY TRACT AND METABOLISM
DRUGS USED IN DIABETES
BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
Combinations of oral blood glucose lowering drugs
ATC A10BD12 ALIMENTARY TRACT AND METABOLISM
DRUGS USED IN DIABETES
BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
Combinations of oral blood glucose lowering drugs
MeSH PA D007004 Hypoglycemic Agents
CHEBI has role CHEBI:50864 insulin-sensitizing drug
FDA EPC N0000175596 Peroxisome Proliferator Receptor alpha Agonist
FDA EPC N0000180186 Peroxisome Proliferator Receptor gamma Agonist
FDA MoA N0000175374 Peroxisome Proliferator-activated Receptor Activity
FDA CS M0199111 PPAR alpha
FDA CS M0199114 PPAR gamma
FDA EPC N0000180190 Thiazolidinedione
FDA CS M0447306 Thiazolidinediones

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Diabetes mellitus type 2 indication 44054006 DOID:9352
Alcoholism contraindication 7200002
Asthenia contraindication 13791008
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
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
Decompensated cardiac failure contraindication 195111005
Disease of liver contraindication 235856003 DOID:409
Hypoglycemic disorder contraindication 237630007
Sepsis syndrome contraindication 238150007
Edema contraindication 267038008
Primary adrenocortical insufficiency contraindication 373662000
Adrenal cortical hypofunction contraindication 386584007 DOID:10493
Fever contraindication 386661006
Surgical procedure contraindication 387713003
Malignant tumor of urinary bladder contraindication 399326009 DOID:11054
Severe diarrhea contraindication 409587002
Breastfeeding (mother) contraindication 413712001
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 6.33 acidic
pKa2 7.15 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 15MG BASE ACTOPLUS MET XR TAKEDA PHARMS USA N022024 May 12, 2009 DISCN TABLET, EXTENDED RELEASE ORAL 6790459 March 17, 2021 ADJUNCT TO DIET AND EXERCISE TO IMPROVE GLYCEMIC CONTROL IN PATIENTS WITH TYPE 2 DIABETES WHO ARE ALREADY TREATED WITH A PIOGLITAZONE AND METFORMIN
EQ 30MG BASE ACTOPLUS MET XR TAKEDA PHARMS USA N022024 May 12, 2009 DISCN TABLET, EXTENDED RELEASE ORAL 6790459 March 17, 2021 ADJUNCT TO DIET AND EXERCISE TO IMPROVE GLYCEMIC CONTROL IN PATIENTS WITH TYPE 2 DIABETES WHO ARE ALREADY TREATED WITH A PIOGLITAZONE AND METFORMIN
EQ 15MG BASE OSENI TAKEDA PHARMS USA N022426 Jan. 25, 2013 RX TABLET ORAL 6329404 June 19, 2021 METHODS OF TREATING DIABETES COMPRISING ADMINISTERING AN INSULIN SENSITIVITY ENHANCER SUCH AS PIOGLITAZONE IN COMBINATION WITH AN INSULIN SECRETION ENHANCER
EQ 30MG BASE OSENI TAKEDA PHARMS USA N022426 Jan. 25, 2013 RX TABLET ORAL 6329404 June 19, 2021 METHODS OF TREATING DIABETES COMPRISING ADMINISTERING AN INSULIN SENSITIVITY ENHANCER SUCH AS PIOGLITAZONE IN COMBINATION WITH AN INSULIN SECRETION ENHANCER
EQ 45MG BASE OSENI TAKEDA PHARMS USA N022426 Jan. 25, 2013 RX TABLET ORAL 6329404 June 19, 2021 METHODS OF TREATING DIABETES COMPRISING ADMINISTERING AN INSULIN SENSITIVITY ENHANCER SUCH AS PIOGLITAZONE IN COMBINATION WITH AN INSULIN SECRETION ENHANCER
EQ 15MG BASE OSENI TAKEDA PHARMS USA N022426 Jan. 25, 2013 RX TABLET ORAL 8173663 March 15, 2025 METHOD OF TREATING DIABETES COMPRISING ADMINISTERING A COMPOUND SUCH AS ALOGLIPTIN
EQ 30MG BASE OSENI TAKEDA PHARMS USA N022426 Jan. 25, 2013 RX TABLET ORAL 8173663 March 15, 2025 METHOD OF TREATING DIABETES COMPRISING ADMINISTERING A COMPOUND SUCH AS ALOGLIPTIN
EQ 45MG BASE OSENI TAKEDA PHARMS USA N022426 Jan. 25, 2013 RX TABLET ORAL 8173663 March 15, 2025 METHOD OF TREATING DIABETES COMPRISING ADMINISTERING A COMPOUND SUCH AS ALOGLIPTIN
EQ 15MG BASE OSENI TAKEDA PHARMS USA N022426 Jan. 25, 2013 RX TABLET ORAL 7807689 June 27, 2028 METHOD OF TREATING DIABETES COMPRISING ADMINISTERING ALOGLIPTIN
EQ 30MG BASE OSENI TAKEDA PHARMS USA N022426 Jan. 25, 2013 RX TABLET ORAL 7807689 June 27, 2028 METHOD OF TREATING DIABETES COMPRISING ADMINISTERING ALOGLIPTIN
EQ 45MG BASE OSENI TAKEDA PHARMS USA N022426 Jan. 25, 2013 RX TABLET ORAL 7807689 June 27, 2028 METHOD OF TREATING DIABETES COMPRISING ADMINISTERING ALOGLIPTIN

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 6.23 WOMBAT-PK CHEMBL
Carbonic anhydrase 2 Enzyme IC50 6.94 DRUG MATRIX
Amine oxidase [flavin-containing] A Enzyme IC50 4.46 DRUG MATRIX
Amine oxidase [flavin-containing] B Enzyme Ki 6.30 CHEMBL
Peroxisome proliferator-activated receptor alpha Nuclear hormone receptor EC50 5.18 CHEMBL
Bile salt export pump Transporter IC50 6.52 CHEMBL
Aldose reductase Enzyme IC50 4.88 DRUG MATRIX
Peroxisome proliferator-activated receptor gamma Transcription factor IC50 6.15 CHEMBL
Enoyl-[acyl-carrier-protein] reductase [NADH] Enzyme IC50 4.10 CHEMBL
Amine oxidase [flavin-containing] B Enzyme Ki 5.68 CHEMBL
Peroxisome proliferator-activated receptor gamma Transcription factor IC50 6.15 CHEMBL
Bile salt export pump Unclassified IC50 5.70 CHEMBL

External reference:

IDSource
D000077205 MESH_DESCRIPTOR_UI
4021165 VUID
N0000148616 NUI
C0071097 UMLSCUI
D00945 KEGG_DRUG
326058001 SNOMEDCT_US
4021165 VANDF
007823 NDDF
d04442 MMSL
33738 RXNORM
395828009 SNOMEDCT_US
29092 MMSL
CHEMBL595 ChEMBL_ID
DB01132 DRUGBANK_ID
CHEMBL1715 ChEMBL_ID
JQT35NPK6C UNII
112529-15-4 SECONDARY_CAS_RN
8N6 PDB_CHEM_ID
P1B PDB_CHEM_ID
CHEBI:8228 CHEBI
6343 INN_ID
4829 PUBCHEM_CID
2694 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Pioglitazone HUMAN PRESCRIPTION DRUG LABEL 1 0093-7271 TABLET 15 mg ORAL ANDA 18 sections
Pioglitazone HUMAN PRESCRIPTION DRUG LABEL 1 0093-7272 TABLET 30 mg ORAL ANDA 18 sections
Pioglitazone HUMAN PRESCRIPTION DRUG LABEL 1 0093-7273 TABLET 45 mg ORAL ANDA 18 sections
Pioglitazone HUMAN PRESCRIPTION DRUG LABEL 1 0781-5420 TABLET 15 mg ORAL ANDA 18 sections
Pioglitazone HUMAN PRESCRIPTION DRUG LABEL 1 0781-5421 TABLET 30 mg ORAL ANDA 18 sections
Pioglitazone HUMAN PRESCRIPTION DRUG LABEL 1 0781-5422 TABLET 45 mg ORAL ANDA 18 sections
Pioglitazone and metformin HUMAN PRESCRIPTION DRUG LABEL 2 0781-5626 TABLET, FILM COATED 15 mg ORAL ANDA 19 sections
Pioglitazone and metformin HUMAN PRESCRIPTION DRUG LABEL 2 0781-5627 TABLET, FILM COATED 15 mg ORAL ANDA 19 sections
Pioglitazone hydrochloride and glimepiride HUMAN PRESCRIPTION DRUG LABEL 2 0781-5634 TABLET 30 mg ORAL ANDA 18 sections
Pioglitazone hydrochloride and glimepiride HUMAN PRESCRIPTION DRUG LABEL 2 0781-5635 TABLET 30 mg ORAL ANDA 18 sections
PIOGLITAZONEHYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 13668-119 TABLET 30 mg ORAL ANDA 19 sections
PIOGLITAZONEHYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 13668-120 TABLET 45 mg ORAL ANDA 19 sections
PIOGLITAZONEHYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 13668-140 TABLET 15 mg ORAL ANDA 19 sections
Pioglitazone HCL and Metformin HCL HUMAN PRESCRIPTION DRUG LABEL 2 13668-280 TABLET 15 mg ORAL ANDA 19 sections
Pioglitazone HCL and Metformin HCL HUMAN PRESCRIPTION DRUG LABEL 2 13668-281 TABLET 15 mg ORAL ANDA 19 sections
PIOGLITAZONE HUMAN PRESCRIPTION DRUG LABEL 1 16729-020 TABLET 15 mg ORAL ANDA 19 sections
PIOGLITAZONE HUMAN PRESCRIPTION DRUG LABEL 1 16729-021 TABLET 30 mg ORAL ANDA 19 sections
PIOGLITAZONE HUMAN PRESCRIPTION DRUG LABEL 1 16729-022 TABLET 45 mg ORAL ANDA 19 sections
Actos HUMAN PRESCRIPTION DRUG LABEL 1 21695-147 TABLET 15 mg ORAL NDA 14 sections
Actos HUMAN PRESCRIPTION DRUG LABEL 1 21695-148 TABLET 30 mg ORAL NDA 14 sections
Pioglitazone HUMAN PRESCRIPTION DRUG LABEL 1 33342-054 TABLET 15 mg ORAL ANDA 19 sections
Pioglitazone HUMAN PRESCRIPTION DRUG LABEL 1 33342-055 TABLET 30 mg ORAL ANDA 19 sections
Pioglitazone HUMAN PRESCRIPTION DRUG LABEL 1 33342-056 TABLET 45 mg ORAL ANDA 19 sections
Pioglitazole and metformin hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 33342-176 TABLET 15 mg ORAL ANDA 19 sections
Pioglitazole and metformin hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 33342-177 TABLET 15 mg ORAL ANDA 19 sections
PIOGLITAZONE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 43063-894 TABLET 15 mg ORAL ANDA 19 sections
PIOGLITAZONE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 43063-895 TABLET 30 mg ORAL ANDA 19 sections
Pioglitazone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 43353-326 TABLET 45 mg ORAL ANDA 19 sections
PIOGLITAZONE HUMAN PRESCRIPTION DRUG LABEL 1 43547-426 TABLET 15 mg ORAL ANDA 19 sections
PIOGLITAZONE HUMAN PRESCRIPTION DRUG LABEL 1 43547-427 TABLET 30 mg ORAL ANDA 19 sections