orlistat 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 1 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class ACVR2A,ACVR2B,ACVRL1,AKT2,AKT3,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,GSK3B,IKBKB,ITK,JAK2,JAK3,MAP2K6,MAP3K21,MAP3K7,MAPK10,MAPK7,MAPK9,MAPKAPK2,MTOR,NTRK2,PDK1,PDK2,PDK4,PDPK1,PIK3CB,PIK3CG,PIM2,PLK1,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TGFBR1,TTK,ZAP70 54
kinase-selectivity-class AXL,EIF2AK3,EPHB4,GRK2,MAP2K6,PLK1,STK33,TEK 8
pfas-class PFAS structural alert (1 = True, 0 = False) 0

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 180.56 16.95 32 6649 536 90621230
Cerebral venous thrombosis 99.75 16.95 25 6656 2303 90619463
Drug interaction 83.15 16.95 102 6579 276351 90345415
Thalamic infarction 74.83 16.95 15 6666 497 90621269
Cholelithiasis 64.52 16.95 43 6638 52463 90569303
Abdominal pain 59.09 16.95 105 6576 395616 90226150
Rectal discharge 55.91 16.95 13 6668 872 90620894
Acute hepatic failure 44.46 16.95 25 6656 22536 90599230
Rectal haemorrhage 43.31 16.95 41 6640 82703 90539063
Crystal nephropathy 42.61 16.95 11 6670 1140 90620626
Jaundice 40.83 16.95 27 6654 32490 90589276
Virologic failure 39.69 16.95 12 6669 2212 90619554
Kidney fibrosis 39.64 16.95 12 6669 2222 90619544
Oxalosis 37.09 16.95 6 6675 56 90621710
Hyperoxaluria 36.48 16.95 7 6674 184 90621582
Menopausal symptoms 35.86 16.95 12 6669 3066 90618700
Slow response to stimuli 33.50 16.95 9 6672 1087 90620679
Haematochezia 31.26 16.95 32 6649 70881 90550885
Abdominal pain upper 30.24 16.95 72 6609 332602 90289164
Renal tubular atrophy 30.07 16.95 8 6673 932 90620834
Nephropathy 29.02 16.95 14 6667 9221 90612545
Urine oxalate increased 28.93 16.95 6 6675 236 90621530
Crying 26.76 16.95 19 6662 25626 90596140
Dysarthria 26.61 16.95 26 6655 54456 90567310
Pancreatitis 26.33 16.95 29 6652 69797 90551969
Liver function test abnormal 26.22 16.95 25 6656 50820 90570946
Muscle spasticity 25.47 16.95 21 6660 35301 90586465
Oropharyngeal blistering 24.66 16.95 7 6674 1036 90620730
Pregnancy on oral contraceptive 24.20 16.95 7 6674 1108 90620658
Hepatic encephalopathy 23.76 16.95 14 6667 13758 90608008
Ear pain 23.56 16.95 25 6656 57677 90564089
Liver iron concentration abnormal 23.10 16.95 4 6677 58 90621708
Pancreatitis acute 22.96 16.95 19 6662 32096 90589670
Drug intolerance 22.87 16.95 3 6678 447588 90174178
Circulatory collapse 22.69 16.95 17 6664 24887 90596879
Lactic acidosis 22.65 16.95 23 6658 50440 90571326
Bradyphrenia 22.30 16.95 11 6670 7601 90614165
Acute kidney injury 21.57 16.95 62 6619 320325 90301441
Gallbladder disorder 21.42 16.95 15 6666 19788 90601978
Alanine aminotransferase increased 21.02 16.95 34 6647 118304 90503462
Diverticulitis 21.02 16.95 21 6660 45166 90576600
Abortion spontaneous 19.60 16.95 22 6659 54034 90567732
Nephrosclerosis 19.55 16.95 6 6675 1163 90620603
Chromaturia 19.52 16.95 14 6667 19173 90602593
Depressed mood 19.17 16.95 21 6660 50201 90571565
Vanishing bile duct syndrome 18.60 16.95 6 6675 1366 90620400
Faeces discoloured 18.20 16.95 14 6667 21306 90600460
Psychomotor retardation 17.32 16.95 8 6673 4781 90616985
Transposition of the great vessels 17.19 16.95 4 6677 269 90621497
Breast enlargement 17.15 16.95 6 6675 1749 90620017
Flatulence 17.02 16.95 18 6663 41349 90580417

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 48.19 25.63 15 1383 6896 42613041
Blood uric acid increased 36.31 25.63 15 1383 15532 42604405
Hyperoxaluria 35.91 25.63 6 1392 164 42619773
Sleep apnoea syndrome 28.54 25.63 14 1384 21594 42598343
Coronary artery disease 25.69 25.63 18 1380 53702 42566235

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
Steatorrhoea 99.57 17.81 21 7040 1040 110581198
Cerebral venous thrombosis 94.95 17.81 25 7036 3237 110579001
Cholelithiasis 84.95 17.81 52 7009 63370 110518868
Hyperoxaluria 68.97 17.81 13 7048 360 110581878
Nephropathy 63.54 17.81 26 7035 13441 110568797
Thalamic infarction 62.47 17.81 15 7046 1337 110580901
Drug interaction 59.67 17.81 111 6950 500072 110082166
Crystal nephropathy 57.75 17.81 15 7046 1841 110580397
Abdominal pain 49.28 17.81 104 6957 512885 110069353
Rectal discharge 44.98 17.81 11 7050 1058 110581180
Acute hepatic failure 44.01 17.81 28 7033 36440 110545798
Kidney fibrosis 41.04 17.81 14 7047 4378 110577860
Menopausal symptoms 40.00 17.81 12 7049 2489 110579749
Oxalosis 39.46 17.81 7 7054 137 110582101
Urine oxalate increased 36.25 17.81 7 7054 221 110582017
Abdominal pain upper 33.72 17.81 71 6990 349040 110233198
Renal tubular atrophy 32.47 17.81 10 7051 2266 110579972
Ear pain 32.40 17.81 27 7034 53199 110529039
Jaundice 29.89 17.81 27 7034 59209 110523029
Slow response to stimuli 29.48 17.81 9 7052 1979 110580259
Vomiting 29.14 17.81 125 6936 910550 109671688
Rectal haemorrhage 29.03 17.81 37 7024 119796 110462442
Muscle spasticity 27.83 17.81 21 7040 35894 110546344
Crying 26.82 17.81 18 7043 25610 110556628
Pancreatitis 24.44 17.81 30 7031 93503 110488735
Pneumonia 24.13 17.81 13 7048 876701 109705537
Liver iron concentration abnormal 23.68 17.81 4 7057 58 110582180
Off label use 22.89 17.81 38 7023 1500147 109082091
Diverticulitis 22.41 17.81 22 7039 53500 110528738
Hepatic steatosis 22.20 17.81 21 7040 48810 110533428
Oropharyngeal blistering 21.80 17.81 6 7055 917 110581321
Pregnancy on oral contraceptive 21.77 17.81 6 7055 922 110581316
Sleep apnoea syndrome 21.52 17.81 19 7042 40428 110541810
Faeces pale 21.18 17.81 8 7053 3349 110578889
Dysarthria 20.41 17.81 26 7035 84095 110498143
Pancreatitis acute 20.23 17.81 22 7039 60252 110521986
Gallbladder disorder 20.18 17.81 14 7047 21015 110561223
Lip swelling 19.69 17.81 20 7041 50647 110531591
Bradyphrenia 19.32 17.81 11 7050 11717 110570521
Hepatitis acute 19.20 17.81 13 7048 18753 110563485
Blood triglycerides increased 18.55 17.81 14 7047 23912 110558326
Death 18.30 17.81 11 7050 698858 109883380
Breast enlargement 18.22 17.81 6 7055 1683 110580555
Diarrhoea 17.86 17.81 129 6932 1139376 109442862

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
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D019440 Anti-Obesity Agents
MeSH PA D057847 Lipid Regulating Agents
FDA EPC N0000175591 Intestinal Lipase Inhibitor
CHEBI has role CHEBI:65001 EC 3.1.1.3 (triacylglycerol lipase) inhibitor
CHEBI has role CHEBI:71476 EC 2.3.1.85 (fatty acid synthase) inhibitor
CHEBI has role CHEBI:74518 anti-obesity agent
CHEBI has role CHEBI:76969 bacterial metabolite

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




🐶 Veterinary Drug Use

None

🐶 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
95M8R751W8 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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 31 sections
ORLISTAT HUMAN PRESCRIPTION DRUG LABEL 1 61269-565 CAPSULE 120 mg ORAL NDA authorized generic 31 sections
ALLI HUMAN OTC DRUG LABEL 1 71610-805 CAPSULE 60 mg ORAL NDA 17 sections