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

Stem definitionDrug idCAS RN
peptides and glycopeptides 4622 851199-59-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • linzess
  • linaclotide
  • constella
  • MD-1100
  • MD-1100 acetate
  • linaclotide acetate
Linaclotide is a guanylate cyclase-C (GC-C) agonist. Both linaclotide and its active metabolite bind to GC-C and act locally on the luminal surface of the intestinal epithelium. Activation of GC-C results in an increase in both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP). Elevation in intracellular cGMP stimulates secretion of chloride and bicarbonate into the intestinal lumen, mainly through activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, resulting in increased intestinal fluid and accelerated transit. In animal models, linaclotide has been shown to both accelerate GI transit and reduce intestinal pain. The linaclotide-induced reduction in visceral pain in animals is thought to be mediated by increased extracellular cGMP, which was shown to decrease the activity of pain-sensing nerves.
  • Molecular weight: 1526.73
  • Formula: C59H79N15O21S6
  • CLOGP: -2.58
  • LIPINSKI: 3
  • HAC: 36
  • HDO: 19
  • TPSA: 573.91
  • ALOGS: -3.34
  • ROTB: 13

Drug dosage:

DoseUnitRoute
0.29 mg O

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Aug. 30, 2012 FDA FOREST LABS LLC
Dec. 19, 2016 PMDA ASTELLAS PHARMA INC.

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
Diarrhoea 119.69 14.27 375 12987 714991 62760669
Product dose omission issue 86.54 14.27 167 13195 234146 63241514
Constipation 80.23 14.27 158 13204 224785 63250875
Abdominal distension 68.95 14.27 88 13274 86527 63389133
Migraine 38.46 14.27 74 13288 103272 63372388
Headache 37.30 14.27 244 13118 632997 62842663
Inappropriate schedule of product administration 36.93 14.27 73 13289 103892 63371768
Product dispensing error 35.88 14.27 24 13338 10281 63465379
Abdominal pain 34.93 14.27 138 13224 293318 63182342
Incorrect dose administered 34.31 14.27 52 13310 59916 63415744
Anal incontinence 32.10 14.27 25 13337 13551 63462109
Illness 28.71 14.27 43 13319 49016 63426644
Pre-existing condition improved 28.22 14.27 19 13343 8225 63467435
Systemic lupus erythematosus 28.16 14.27 5 13357 208913 63266747
Maternal exposure during pregnancy 28.11 14.27 6 13356 220056 63255604
Completed suicide 27.48 14.27 80 13282 145593 63330067
Off label use 27.30 14.27 238 13124 674224 62801436
General physical health deterioration 26.75 14.27 5 13357 201397 63274263
Product physical issue 25.97 14.27 15 13347 4965 63470695
Feeling abnormal 25.63 14.27 79 13283 148313 63327347
Flatulence 25.62 14.27 34 13328 34668 63440992
Glossodynia 24.72 14.27 4 13358 178872 63296788
Treatment failure 24.28 14.27 6 13356 199037 63276623
Product packaging quantity issue 22.33 14.27 9 13353 1350 63474310
Contraindicated product administered 22.21 14.27 9 13353 217639 63258021
Product storage error 22.02 14.27 21 13341 14935 63460725
Wound 21.79 14.27 4 13358 163259 63312401
Surgery 21.76 14.27 32 13330 35880 63439780
Drug intolerance 19.21 14.27 22 13340 308639 63167021
Arthropathy 19.11 14.27 13 13349 234779 63240881
Rheumatoid arthritis 18.18 14.27 16 13346 253803 63221857
Infusion related reaction 18.17 14.27 15 13347 245506 63230154
Thrombocytopenia 17.59 14.27 5 13357 151152 63324508
Malaise 17.39 14.27 148 13214 415806 63059854
Multiple sclerosis relapse 17.15 14.27 34 13328 48444 63427216
Volvulus 16.84 14.27 8 13354 1778 63473882
Anxiety 16.69 14.27 90 13272 217451 63258209
Nausea 16.68 14.27 262 13100 854209 62621451
Intervertebral disc compression 16.52 14.27 7 13355 1191 63474469
Impaired gastric emptying 16.15 14.27 15 13347 10317 63465343
Insurance issue 16.07 14.27 12 13350 6109 63469551
Muscle spasms 15.84 14.27 70 13292 156080 63319580
Subacute hepatic failure 15.73 14.27 4 13358 134 63475526
Therapy interrupted 15.60 14.27 26 13336 32429 63443231
Blood potassium decreased 15.50 14.27 30 13332 41996 63433664
Lymph node pain 15.29 14.27 7 13355 1431 63474229
Intestinal obstruction 15.18 14.27 25 13337 30874 63444786
Nervousness 15.13 14.27 25 13337 30954 63444706
COVID-19 14.90 14.27 55 13307 113048 63362612
Lower respiratory tract infection 14.28 14.27 5 13357 132302 63343358

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
Diarrhoea 97.72 22.48 132 2503 389780 34564516
Off label use 41.90 22.48 95 2540 419429 34534867
Prescribed underdose 41.88 22.48 18 2617 8915 34945381
Drug ineffective 37.61 22.48 96 2539 456655 34497641
Inappropriate schedule of product administration 32.34 22.48 31 2604 62265 34892031
Constipation 27.45 22.48 42 2593 136940 34817356
Urinary retention 24.60 22.48 21 2614 36267 34918029
Incorrect dose administered 22.61 22.48 21 2614 40494 34913802

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
Diarrhoea 77.82 14.47 291 11256 880198 78852643
Product dose omission issue 72.43 14.47 129 11418 247408 79485433
Constipation 72.16 14.47 139 11408 282911 79449930
Headache 47.81 14.47 204 11343 653568 79079273
Abdominal distension 41.05 14.47 67 11480 119583 79613258
Incorrect dose administered 37.95 14.47 51 11496 76579 79656262
Inappropriate schedule of product administration 29.63 14.47 62 11485 133566 79599275
Completed suicide 26.47 14.47 87 11460 245680 79487161
Abdominal pain 25.66 14.47 118 11429 389451 79343390
Acute kidney injury 23.91 14.47 24 11523 519380 79213461
Migraine 23.49 14.47 44 11503 87449 79645392
Malaise 22.99 14.47 135 11412 489734 79243107
Off label use 22.59 14.47 215 11332 907000 78825841
Nausea 22.45 14.47 224 11323 956972 78775869
Feeling abnormal 20.51 14.47 60 11487 159139 79573702
Flatulence 20.48 14.47 28 11519 42696 79690145
Multiple sclerosis relapse 20.09 14.47 29 11518 46504 79686337
Dizziness 19.71 14.47 137 11410 526304 79206537
Anal incontinence 19.26 14.47 18 11529 18150 79714691
General physical health deterioration 19.05 14.47 8 11539 275230 79457611
Intervertebral disc compression 18.42 14.47 7 11540 1309 79731532
Urinary tract infection 17.94 14.47 83 11464 274429 79458412
Anxiety 17.63 14.47 77 11470 248435 79484406
Neutropenia 17.43 14.47 10 11537 287700 79445141
Lymph node pain 17.31 14.47 7 11540 1543 79731298
Tooth infection 16.85 14.47 17 11530 18815 79714026
Oesophageal hypomotility 16.68 14.47 4 11543 154 79732687
Nervousness 16.17 14.47 22 11525 33393 79699448
Febrile neutropenia 15.53 14.47 7 11540 230992 79501849
Dihydrotestosterone increased 15.40 14.47 3 11544 42 79732799

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC A06AX04 ALIMENTARY TRACT AND METABOLISM
DRUGS FOR CONSTIPATION
DRUGS FOR CONSTIPATION
Other drugs for constipation
MeSH PA D020536 Enzyme Activators
MeSH PA D005765 Gastrointestinal Agents
MeSH PA D000074268 Guanylyl Cyclase C Agonists
FDA MoA N0000185499 Guanylate Cyclase Activators
FDA EPC N0000185500 Guanylate Cyclase-C Agonist
CHEBI has role CHEBI:68553 GC-C agonists

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

DiseaseRelationSNOMED_IDDOID
Irritable bowel syndrome indication 10743008 DOID:9778
Chronic idiopathic constipation indication 82934008
Irritable bowel syndrome characterized by constipation indication 440630006




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.46 acidic
pKa2 4.13 acidic
pKa3 9.65 acidic
pKa4 10.31 acidic
pKa5 12.22 acidic
pKa6 12.57 acidic
pKa7 12.94 acidic
pKa8 13.17 acidic
pKa9 13.37 acidic
pKa10 13.69 acidic
pKa11 13.86 acidic
pKa12 13.98 acidic
pKa13 6.73 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
145MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 8110553 Jan. 28, 2024 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULTS
290MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 8110553 Jan. 28, 2024 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULTS
72MCG LINZESS ABBVIE N202811 Jan. 25, 2017 RX CAPSULE ORAL 8110553 Jan. 28, 2024 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
72MCG LINZESS ABBVIE N202811 Jan. 25, 2017 RX CAPSULE ORAL 8110553 Jan. 28, 2024 TREATMENT OF FUNCTIONAL CONSTIPATION IN PEDIATRIC PATIENTS 6 TO 17 YEARS OF AGE
145MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 7304036 Aug. 30, 2026 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
145MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 7304036 Aug. 30, 2026 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULTS
290MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 7304036 Aug. 30, 2026 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
290MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 7304036 Aug. 30, 2026 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULTS
72MCG LINZESS ABBVIE N202811 Jan. 25, 2017 RX CAPSULE ORAL 7304036 Aug. 30, 2026 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
72MCG LINZESS ABBVIE N202811 Jan. 25, 2017 RX CAPSULE ORAL 7304036 Aug. 30, 2026 TREATMENT OF FUNCTIONAL CONSTIPATION IN PEDIATRIC PATIENTS 6 TO 17 YEARS OF AGE
72MCG LINZESS ABBVIE N202811 Jan. 25, 2017 RX CAPSULE ORAL 8933030 Feb. 17, 2031 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
72MCG LINZESS ABBVIE N202811 Jan. 25, 2017 RX CAPSULE ORAL 8933030 Feb. 17, 2031 TREATMENT OF FUNCTIONAL CONSTIPATION IN PEDIATRIC PATIENTS 6 TO 17 YEARS OF AGE
72MCG LINZESS ABBVIE N202811 Jan. 25, 2017 RX CAPSULE ORAL 10702576 Aug. 11, 2031 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
72MCG LINZESS ABBVIE N202811 Jan. 25, 2017 RX CAPSULE ORAL 10702576 Aug. 11, 2031 TREATMENT OF FUNCTIONAL CONSTIPATION IN PEDIATRIC PATIENTS 6 TO 17 YEARS OF AGE
145MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 8748573 Oct. 30, 2031 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
145MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 8748573 Oct. 30, 2031 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULT PATIENTS.
290MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 8748573 Oct. 30, 2031 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
290MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 8748573 Oct. 30, 2031 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULT PATIENTS.
145MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 9708371 Aug. 16, 2033 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
145MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 9708371 Aug. 16, 2033 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULT PATIENTS.
290MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 9708371 Aug. 16, 2033 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULT PATIENTS.
72MCG LINZESS ABBVIE N202811 Jan. 25, 2017 RX CAPSULE ORAL 9708371 Aug. 16, 2033 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
72MCG LINZESS ABBVIE N202811 Jan. 25, 2017 RX CAPSULE ORAL 9708371 Aug. 16, 2033 TREATMENT OF FUNCTIONAL CONSTIPATION IN PEDIATRIC PATIENTS 6 TO 17 YEARS OF AGE

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Heat-stable enterotoxin receptor Enzyme AGONIST Ki 8.91 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Heat-stable enterotoxin receptor Enzyme AGONIST Ki 8.38 IUPHAR

External reference:

IDSource
D06612 KEGG_DRUG
4031965 VANDF
CHEBI:68551 CHEBI
CHEMBL3301675 ChEMBL_ID
C523483 MESH_SUPPLEMENTAL_RECORD_UI
5017 IUPHAR_LIGAND_ID
8802 INN_ID
851199-60-5 SECONDARY_CAS_RN
DB08890 DRUGBANK_ID
N0TXR0XR5X UNII
1307404 RXNORM
192786 MMSL
28804 MMSL
d07902 MMSL
014633 NDDF
703126002 SNOMEDCT_US
703686003 SNOMEDCT_US
C2000261 UMLSCUI
CHEMBL3301676 ChEMBL_ID
16158208 PUBCHEM_CID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Linzess HUMAN PRESCRIPTION DRUG LABEL 1 0456-1201 CAPSULE, GELATIN COATED 145 ug ORAL NDA 29 sections
Linzess HUMAN PRESCRIPTION DRUG LABEL 1 0456-1201 CAPSULE, GELATIN COATED 145 ug ORAL NDA 29 sections
Linzess HUMAN PRESCRIPTION DRUG LABEL 1 0456-1202 CAPSULE, GELATIN COATED 290 ug ORAL NDA 29 sections
Linzess HUMAN PRESCRIPTION DRUG LABEL 1 0456-1202 CAPSULE, GELATIN COATED 290 ug ORAL NDA 29 sections
Linzess HUMAN PRESCRIPTION DRUG LABEL 1 0456-1203 CAPSULE, GELATIN COATED 72 ug ORAL NDA 29 sections
Linzess HUMAN PRESCRIPTION DRUG LABEL 1 0456-1203 CAPSULE, GELATIN COATED 72 ug ORAL NDA 29 sections