orlistat 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: 8.61
  • 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 ┬ÁM/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 232.80 32.56 31 974 77 2357003
Abdominal pain 182.56 32.56 70 935 34304 2322776
Rectal haemorrhage 161.01 32.56 42 963 5814 2351266
Diarrhoea 136.88 32.56 75 930 83489 2273591
Abdominal pain upper 131.34 32.56 49 956 22051 2335029
Haematochezia 112.43 32.56 31 974 5264 2351816
Cholelithiasis 105.09 32.56 30 975 5773 2351307
Drug interaction 98.14 32.56 43 962 29120 2327960
Rectal discharge 84.21 32.56 13 992 113 2356967
Alanine aminotransferase increased 79.08 32.56 30 975 14002 2343078
Acute hepatic failure 72.67 32.56 19 986 2623 2354457
Constipation 69.74 32.56 31 974 21598 2335482
Nausea 67.30 32.56 54 951 112135 2244945
Flatulence 66.87 32.56 20 985 4505 2352575
Nephropathy 65.38 32.56 14 991 816 2356264
Acute kidney injury 64.95 32.56 32 973 28090 2328990
Vomiting 64.29 32.56 44 961 71558 2285522
Diverticulitis 64.11 32.56 19 986 4146 2352934
Hepatic enzyme increased 62.63 32.56 23 982 9779 2347301
Aspartate aminotransferase increased 60.48 32.56 24 981 12588 2344492
Dizziness 57.25 32.56 38 967 58627 2298453
Pancreatitis 51.75 32.56 19 986 8060 2349020
Headache 50.90 32.56 40 965 80139 2276941
Abdominal distension 50.54 32.56 20 985 10391 2346689
Obesity 46.84 32.56 12 993 1524 2355556
Abortion spontaneous 45.60 32.56 20 985 13425 2343655
Dyspnoea 45.08 32.56 37 968 78696 2278384
Exposure during pregnancy 44.57 32.56 24 981 25195 2331885
Pancreatitis acute 44.06 32.56 14 991 3839 2353241
Jaundice 42.97 32.56 15 990 5493 2351587
Malaise 42.41 32.56 31 974 55554 2301526
Faeces discoloured 41.74 32.56 12 993 2347 2354733
Transaminases increased 41.66 32.56 14 991 4573 2352507
Chromaturia 39.91 32.56 12 993 2741 2354339
Fatigue 38.64 32.56 35 970 84838 2272242
Nephrolithiasis 37.86 32.56 13 992 4530 2352550
Renal failure 37.76 32.56 19 986 17330 2339750
Hepatitis 37.24 32.56 14 991 6323 2350757
Product quality issue 36.35 32.56 16 989 10813 2346267
Drug ineffective 35.10 32.56 36 969 101588 2255492
Hepatic failure 35.00 32.56 13 992 5676 2351404
Hepatic steatosis 33.96 32.56 11 994 3202 2353878
Ill-defined disorder 33.42 32.56 11 994 3367 2353713
Defaecation urgency 32.63 32.56 7 998 410 2356670

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 75.21 36.93 14 255 932 1745580
Abdominal pain 38.68 36.93 16 253 21474 1725038
Vomiting 38.63 36.93 19 250 38296 1708216
Hyperoxaluria 36.96 36.93 5 264 39 1746473

Pharmacologic Action:

SourceCodeDescription
ATC A08AB01 ALIMENTARY TRACT AND METABOLISM
ANTIOBESITY PREPARATIONS, EXCL. DIET PRODUCTS
ANTIOBESITY PREPARATIONS, EXCL. DIET PRODUCTS
Peripherally acting antiobesity products
FDA EPC N0000175591 Intestinal Lipase Inhibitor
FDA MoA N0000009916 Lipase Inhibitors
MeSH PA D019440 Anti-Obesity Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D057847 Lipid Regulating Agents

Drug Use (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

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
Monoacylglycerol lipase ABHD12 Enzyme IC50 7.10 CHEMBL
Monoacylglycerol lipase ABHD6 Enzyme IC50 7.32 CHEMBL
Sn1-specific diacylglycerol lipase alpha Enzyme IC50 8 CHEMBL
Abhydrolase domain-containing protein 16A Enzyme IC50 7.52 CHEMBL
Platelet-activating factor acetylhydrolase Enzyme IC50 7.30 CHEMBL
Sn1-specific diacylglycerol lipase beta Enzyme IC50 7.22 CHEMBL
Cannabinoid receptor 1 GPCR Ki 5.60 CHEMBL
Fatty-acid amide hydrolase 1 Enzyme IC50 8 CHEMBL
Pancreatic triacylglycerol lipase Enzyme IC50 6.66 CHEMBL

External reference:

IDSource
D000077403 MESH_DESCRIPTOR_UI
4021159 VUID
N0000148610 NUI
C0076275 UMLSCUI
D04028 KEGG_DRUG
116093009 SNOMEDCT_US
4021159 VANDF
007654 NDDF
d04429 MMSL
8088 MMSL
37925 RXNORM
387007000 SNOMEDCT_US
95M8R751W8 UNII
6318 INN_ID
CHEMBL175247 ChEMBL_ID
DB01083 DRUGBANK_ID
CHEBI:94686 CHEBI
3034010 PUBCHEM_CID
5277 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ALLI HUMAN OTC DRUG LABEL 1 0135-0461 CAPSULE 60 mg ORAL NDA 9 sections
Xenical HUMAN PRESCRIPTION DRUG LABEL 1 61269-460 CAPSULE 120 mg ORAL NDA 20 sections