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rosiglitazone 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
peroxisome proliferator activating receptor-gamma (PPAR-gamma) agonists, thiazolidinedione derivatives	2405	122320-73-4

Description:

Molecule	Description
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

Molecule

Description

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:

Dose	Unit	Route
6	mg	O

ADMET properties:

Property	Value	Reference
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 µM/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:

Date	Agency	Company	Orphan
May 25, 1999	FDA	SB PHARMCO

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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:

Source	Code	Description
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|

Disease	Relation	SNOMED_ID	DOID
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

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Peroxisome proliferator-activated receptor gamma	Nuclear hormone receptor	P37231	PPARG_HUMAN	AGONIST	EC50	7.04	WOMBAT-PK	CHEMBL
Carbonic anhydrase 2	Enzyme	P00918	CAH2_HUMAN		IC50	5.39	DRUG MATRIX
Bile salt export pump	Transporter	O95342	ABCBB_HUMAN		IC50	5.19	CHEMBL
Amine oxidase [flavin-containing] B	Enzyme	P27338	AOFB_HUMAN		Ki	5.38	CHEMBL
Amine oxidase [flavin-containing] A	Enzyme	P21397	AOFA_HUMAN		Ki	4.56	CHEMBL
Peroxisome proliferator-activated receptor alpha	Nuclear hormone receptor	Q07869	PPARA_HUMAN		EC50	7.41	CHEMBL
Retinoic acid receptor RXR-alpha	Nuclear hormone receptor	P19793	RXRA_HUMAN		Kd	4.82	CHEMBL
Retinoic acid receptor gamma	Nuclear hormone receptor	P13631	RARG_HUMAN		Ki	5	CHEMBL
Thromboxane-A synthase	Enzyme	P24557	THAS_HUMAN		IC50	5.45	DRUG MATRIX
Peroxisome proliferator-activated receptor delta	Nuclear hormone receptor	Q03181	PPARD_HUMAN		EC50	5.44	CHEMBL
Free fatty acid receptor 1	GPCR	O14842	FFAR1_HUMAN	AGONIST	EC50	5.60	IUPHAR
Short transient receptor potential channel 5	Ion channel	Q9UL62	TRPC5_HUMAN	ACTIVATOR	EC50	4.51	IUPHAR
Sodium/bile acid cotransporter	Transporter	Q14973	NTCP_HUMAN		IC50	5.29	CHEMBL
CDGSH iron-sulfur domain-containing protein 1	Unclassified	Q9NZ45	CISD1_HUMAN		Ki	7.51	CHEMBL
Potassium voltage-gated channel subfamily H member 2	Ion channel	Q12809	KCNH2_HUMAN		IC50	4.53	CHEMBL
CDGSH iron-sulfur domain-containing protein 2	Unclassified	Q8N5K1	CISD2_HUMAN		IC50	5.64	CHEMBL
Amine oxidase [flavin-containing] B	Enzyme		AOFB_RAT		Ki	5.24	CHEMBL
Amine oxidase [flavin-containing] A	Enzyme		AOFA_RAT		Ki	4.49	CHEMBL
Peroxisome proliferator-activated receptor alpha	Transcription factor		PPARA_MOUSE		IC50	7.10	CHEMBL
Peroxisome proliferator-activated receptor gamma	Transcription factor		PPARG_MOUSE		EC50	7.52	CHEMBL
Type-1A angiotensin II receptor	GPCR		AGTRA_RAT		Ki	9.64	CHEMBL
Bile salt export pump	Transporter		ABCBB_RAT		IC50	4.40	CHEMBL
CDGSH iron-sulfur domain-containing protein 1	Unclassified		CISD1_RAT		IC50	5.96	CHEMBL

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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