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

Stem definitionDrug idCAS RN
gastrointestinal lipase inhibitors 1996 96829-58-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • orlistat
  • tetrahydrolipstatin
  • xenical
  • alli
  • tetrahydrolipastatin
A lactone derivative of LEUCINE that acts as a pancreatic lipase inhibitor to limit the absorption of dietary fat; it is used in the management of obesity.
  • Molecular weight: 495.75
  • Formula: C29H53NO5
  • CLOGP: 8.94
  • LIPINSKI: 1
  • HAC: 6
  • HDO: 1
  • TPSA: 81.70
  • ALOGS: -6.73
  • ROTB: 23

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
0.36 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 4 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 1 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 9.22 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 1 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

DateAgencyCompanyOrphan
April 23, 1999 FDA HOFFMANN LA ROCHE

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
Steatorrhoea 169.52 17.06 31 6114 468 63482409
Cerebral venous thrombosis 95.87 17.06 25 6120 2049 63480828
Thalamic infarction 71.35 17.06 15 6130 477 63482400
Drug interaction 68.77 17.06 97 6048 229034 63253843
Cholelithiasis 56.28 17.06 41 6104 43884 63438993
Abdominal pain 55.97 17.06 101 6044 293355 63189522
Rectal discharge 50.80 17.06 12 6133 654 63482223
Rectal haemorrhage 50.11 17.06 40 6105 48990 63433887
Crystal nephropathy 41.89 17.06 11 6134 925 63481952
Abdominal pain upper 37.95 17.06 70 6075 206374 63276503
Oxalosis 36.51 17.06 6 6139 46 63482831
Menopausal symptoms 35.28 17.06 12 6133 2449 63480428
Hyperoxaluria 34.88 17.06 7 6138 176 63482701
Kidney fibrosis 34.31 17.06 11 6134 1870 63481007
Jaundice 32.33 17.06 25 6120 29226 63453651
Slow response to stimuli 31.62 17.06 9 6136 1023 63481854
Haematochezia 31.50 17.06 32 6113 53512 63429365
Nephropathy 30.41 17.06 14 6131 6327 63476550
Virologic failure 30.35 17.06 10 6135 1852 63481025
Acute hepatic failure 27.85 17.06 19 6126 18308 63464569
Urine oxalate increased 26.83 17.06 6 6139 256 63482621
Renal tubular atrophy 24.82 17.06 7 6138 769 63482108
Crying 23.74 17.06 19 6126 23324 63459553
Oropharyngeal blistering 23.73 17.06 7 6138 902 63481975
Pancreatitis 23.00 17.06 26 6119 49029 63433848
Pregnancy on oral contraceptive 22.82 17.06 7 6138 1030 63481847
Muscle spasticity 22.72 17.06 18 6127 21776 63461101
Liver iron concentration abnormal 22.02 17.06 4 6141 58 63482819
Ear pain 21.99 17.06 22 6123 36096 63446781
Lactic acidosis 20.92 17.06 22 6123 38265 63444612
Vanishing bile duct syndrome 20.71 17.06 6 6139 726 63482151
Bradyphrenia 20.38 17.06 11 6134 6969 63475908
Nephrosclerosis 18.55 17.06 6 6139 1048 63481829
Circulatory collapse 18.45 17.06 16 6129 21922 63460955
Gallbladder disorder 18.45 17.06 15 6130 18827 63464050
Liver function test abnormal 18.39 17.06 23 6122 48158 63434719
Depressed mood 18.32 17.06 21 6124 40170 63442707
Alanine aminotransferase increased 17.55 17.06 34 6111 103736 63379141
Pancreatitis acute 17.38 17.06 17 6128 27149 63455728
Abortion spontaneous 17.18 17.06 22 6123 47173 63435704

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
Nephropathy 44.50 24.87 14 1280 5903 34949734
Blood uric acid increased 41.54 24.87 15 1279 9609 34946028
Hyperoxaluria 29.59 24.87 5 1289 129 34955508
Coronary artery disease 25.46 24.87 18 1276 48287 34907350

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
Cerebral venous thrombosis 93.29 17.41 25 6427 2728 79735208
Steatorrhoea 91.96 17.41 20 6432 901 79737035
Cholelithiasis 70.23 17.41 47 6405 52617 79685319
Nephropathy 62.27 17.41 25 6427 9713 79728223
Hyperoxaluria 61.59 17.41 12 6440 311 79737625
Thalamic infarction 59.44 17.41 15 6437 1292 79736644
Crystal nephropathy 48.29 17.41 13 6439 1442 79736494
Drug interaction 47.51 17.41 104 6348 415079 79322857
Abdominal pain 46.18 17.41 99 6353 389470 79348466
Rectal discharge 40.38 17.41 10 6442 798 79737138
Abdominal pain upper 40.27 17.41 68 6384 223751 79514185
Menopausal symptoms 40.07 17.41 12 6440 1951 79735985
Oxalosis 39.38 17.41 7 6445 108 79737828
Kidney fibrosis 36.92 17.41 13 6439 3522 79734414
Urine oxalate increased 33.98 17.41 7 6445 242 79737694
Rectal haemorrhage 33.72 17.41 36 6416 76264 79661672
Ear pain 31.49 17.41 24 6428 32845 79705091
Slow response to stimuli 28.14 17.41 9 6443 1816 79736120
Renal tubular atrophy 28.00 17.41 9 6443 1847 79736089
Acute hepatic failure 26.70 17.41 21 6431 30092 79707844
Muscle spasticity 25.84 17.41 18 6434 21457 79716479
Vomiting 25.61 17.41 114 6338 665714 79072222
Crying 24.70 17.41 18 6434 23025 79714911
Jaundice 23.26 17.41 25 6427 53324 79684612
Liver iron concentration abnormal 22.73 17.41 4 6448 58 79737878
Pneumonia 22.18 17.41 13 6439 660233 79077703
Oropharyngeal blistering 21.36 17.41 6 6446 778 79737158
Pancreatitis 21.31 17.41 27 6425 68548 79669388
Pregnancy on oral contraceptive 20.92 17.41 6 6446 839 79737097
Death 19.23 17.41 11 6441 566503 79171433
Diverticulitis 19.11 17.41 21 6431 45915 79692021
Hepatic steatosis 18.81 17.41 19 6433 37719 79700217
Off label use 18.58 17.41 28 6424 907187 78830749
Gallbladder disorder 18.26 17.41 14 6438 19326 79718610
Bradyphrenia 17.89 17.41 11 6441 10629 79727307
Lip swelling 17.53 17.41 19 6433 40892 79697044
Sleep apnoea syndrome 17.52 17.41 18 6434 36460 79701476

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC A08AB01 ALIMENTARY TRACT AND METABOLISM
ANTIOBESITY PREPARATIONS, EXCL. DIET PRODUCTS
ANTIOBESITY PREPARATIONS, EXCL. DIET PRODUCTS
Peripherally acting antiobesity products
FDA MoA N0000009916 Lipase Inhibitors
FDA EPC N0000175591 Intestinal Lipase Inhibitor
MeSH PA D019440 Anti-Obesity Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D057847 Lipid Regulating Agents
CHEBI has role CHEBI:65001 tributyrin esterase inhibitor
CHEBI has role CHEBI:71476 fatty acid synthase inhibitors
CHEBI has role CHEBI:74518 anti-obestic agents

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

DiseaseRelationSNOMED_IDDOID
Obesity indication 414916001 DOID:9970
Primary hyperoxaluria contraindication 17901006 DOID:2977
Obstruction of bile duct contraindication 30144000
Anorexia nervosa contraindication 56882008 DOID:8689
Hepatic failure contraindication 59927004
Bulimia nervosa contraindication 78004001
Vitamin deficiency contraindication 85670002
Hepatic necrosis contraindication 87248009
Liver function tests abnormal contraindication 166603001
Drug-induced hepatitis contraindication 235876009
Malabsorption States contraindication
Calcium Oxalate Renal Calculi 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 13.77 acidic

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
Pancreatic triacylglycerol lipase Enzyme INHIBITOR IC50 8.90 IUPHAR DRUG LABEL
Gastric triacylglycerol lipase Enzyme INHIBITOR CHEMBL DRUG LABEL
Fatty acid synthase Enzyme IC50 5.33 CHEMBL
Sn1-specific diacylglycerol lipase alpha Enzyme IC50 8 CHEMBL
Sn1-specific diacylglycerol lipase beta Enzyme IC50 7.22 CHEMBL
Abhydrolase domain-containing protein 16A Enzyme IC50 7.52 CHEMBL
Monoacylglycerol lipase ABHD12 Enzyme IC50 7.10 CHEMBL
Cannabinoid receptor 1 GPCR Ki 5.60 CHEMBL
Monoacylglycerol lipase ABHD6 Enzyme IC50 7.32 CHEMBL
Hepatic triacylglycerol lipase Enzyme IC50 8.52 CHEMBL
Endothelial lipase Enzyme IC50 8.22 CHEMBL
Platelet-activating factor acetylhydrolase Enzyme IC50 7.30 CHEMBL
Lipoprotein lipase Enzyme IC50 7.18 CHEMBL
Fatty-acid amide hydrolase 1 Enzyme IC50 8 CHEMBL
Pancreatic triacylglycerol lipase Enzyme IC50 6.66 CHEMBL
Sn1-specific diacylglycerol lipase alpha Enzyme IC50 7.70 CHEMBL

External reference:

IDSource
4021159 VUID
N0000148610 NUI
D04028 KEGG_DRUG
4021159 VANDF
C0076275 UMLSCUI
CHEBI:94686 CHEBI
CHEMBL175247 ChEMBL_ID
D000077403 MESH_DESCRIPTOR_UI
DB01083 DRUGBANK_ID
5277 IUPHAR_LIGAND_ID
6318 INN_ID
95M8R751W8 UNII
3034010 PUBCHEM_CID
226918 RXNORM
109396 MMSL
186669 MMSL
29932 MMSL
8088 MMSL
d04429 MMSL
007654 NDDF
116093009 SNOMEDCT_US
387007000 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ALLI HUMAN OTC DRUG LABEL 1 0135-0461 CAPSULE 60 mg ORAL NDA 17 sections
ALLI HUMAN OTC DRUG LABEL 1 0135-0461 CAPSULE 60 mg ORAL NDA 17 sections
Xenical HUMAN PRESCRIPTION DRUG LABEL 1 61269-460 CAPSULE 120 mg ORAL NDA 30 sections
Xenical HUMAN PRESCRIPTION DRUG LABEL 1 61269-460 CAPSULE 120 mg ORAL NDA 30 sections
ORLISTAT HUMAN PRESCRIPTION DRUG LABEL 1 61269-565 CAPSULE 120 mg ORAL NDA authorized generic 30 sections
ORLISTAT HUMAN PRESCRIPTION DRUG LABEL 1 61269-565 CAPSULE 120 mg ORAL NDA authorized generic 30 sections