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 136.65 14.74 347 10307 588129 50006341
Product dose omission issue 65.39 14.74 129 10525 183709 50410761
Abdominal distension 61.10 14.74 76 10578 72827 50521643
Constipation 60.90 14.74 126 10528 185582 50408888
Inappropriate schedule of product administration 37.91 14.74 60 10594 71771 50522699
Off label use 37.83 14.74 198 10456 474228 50120242
Incorrect dose administered 35.10 14.74 47 10607 48367 50546103
Headache 34.76 14.74 203 10451 506332 50088138
Abdominal pain 33.91 14.74 118 10536 236110 50358360
Migraine 29.35 14.74 55 10599 75225 50519245
Product dispensing error 26.92 14.74 19 10635 8872 50585598
Anal incontinence 26.82 14.74 21 10633 11469 50583001
Flatulence 25.11 14.74 31 10623 29427 50565043
Pre-existing condition improved 23.44 14.74 16 10638 7081 50587389
Product physical issue 22.46 14.74 13 10641 4319 50590151
Intentional product misuse 20.57 14.74 36 10618 46698 50547772
Feeling abnormal 19.11 14.74 64 10590 125428 50469042
Anxiety 18.32 14.74 80 10574 177526 50416944
Muscle spasms 18.21 14.74 63 10591 125490 50468980
Intervertebral disc compression 18.07 14.74 7 10647 946 50593524
General physical health deterioration 17.96 14.74 4 10650 142430 50452040
Maternal exposure during pregnancy 17.33 14.74 6 10648 159772 50434698
Product packaging quantity issue 17.22 14.74 7 10647 1073 50593397
Multiple sclerosis relapse 16.25 14.74 31 10623 42933 50551537
Subacute hepatic failure 16.09 14.74 4 10650 122 50594348
Lymph node pain 15.99 14.74 7 10647 1288 50593182
Product storage error 15.82 14.74 16 10638 12208 50582262
Systemic lupus erythematosus 15.74 14.74 5 10649 140617 50453853
Surgery 15.60 14.74 25 10629 30180 50564290
Malaise 15.43 14.74 122 10532 335410 50259060
Treatment failure 15.22 14.74 5 10649 137632 50456838
Glossodynia 15.07 14.74 3 10651 115566 50478904
Dysphagia 15.01 14.74 43 10611 77475 50516995

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 99.12 25.61 119 1984 332579 29239845
Prescribed underdose 45.30 25.61 18 2085 7768 29564656
Off label use 39.91 25.61 74 2029 300726 29271698
Drug ineffective 38.16 25.61 81 2022 363089 29209335
Inappropriate schedule of product administration 34.20 25.61 27 2076 44445 29527979
Incorrect dose administered 27.46 25.61 21 2082 32963 29539461
Urinary retention 25.88 25.61 20 2083 31878 29540546

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 85.07 16.22 262 9041 722442 63766987
Product dose omission issue 56.63 16.22 101 9202 194646 64294783
Constipation 53.17 16.22 108 9195 229229 64260200
Headache 45.34 16.22 173 9130 529294 63960135
Incorrect dose administered 42.47 16.22 48 9255 60717 64428712
Abdominal distension 37.61 16.22 57 9246 95937 64393492
Inappropriate schedule of product administration 33.63 16.22 53 9250 92233 64397196
Off label use 29.26 16.22 173 9130 632633 63856796
Abdominal pain 24.15 16.22 99 9204 312276 64177153
Dizziness 22.73 16.22 122 9181 430041 64059388
Anxiety 22.24 16.22 72 9231 202577 64286852
Flatulence 21.29 16.22 26 9277 35640 64453789
Nausea 20.78 16.22 188 9115 785612 63703817
Malaise 20.67 16.22 112 9191 396135 64093294
Intervertebral disc compression 20.25 16.22 7 9296 1004 64488425
Acute kidney injury 20.24 16.22 21 9282 449219 64040210
Multiple sclerosis relapse 19.87 16.22 27 9276 41108 64448321
Lymph node pain 18.26 16.22 7 9296 1345 64488084
Feeling abnormal 16.99 16.22 50 9253 133552 64355877

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 ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 8110553 Jan. 28, 2024 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULTS
290MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 8110553 Jan. 28, 2024 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULTS
72MCG LINZESS ALLERGAN N202811 Jan. 25, 2017 RX CAPSULE ORAL 8110553 Jan. 28, 2024 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
145MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 7304036 Aug. 30, 2026 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
145MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 7304036 Aug. 30, 2026 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULTS
290MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 7304036 Aug. 30, 2026 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
290MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 7304036 Aug. 30, 2026 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULTS
72MCG LINZESS ALLERGAN N202811 Jan. 25, 2017 RX CAPSULE ORAL 7304036 Aug. 30, 2026 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
72MCG LINZESS ALLERGAN N202811 Jan. 25, 2017 RX CAPSULE ORAL 8933030 Feb. 17, 2031 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
72MCG LINZESS ALLERGAN N202811 Jan. 25, 2017 RX CAPSULE ORAL 10702576 Aug. 11, 2031 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
145MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 8748573 Oct. 30, 2031 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
145MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 8748573 Oct. 30, 2031 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULT PATIENTS.
290MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 8748573 Oct. 30, 2031 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
290MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 8748573 Oct. 30, 2031 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULT PATIENTS.
145MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 9708371 Aug. 16, 2033 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
145MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 9708371 Aug. 16, 2033 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULT PATIENTS.
290MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 9708371 Aug. 16, 2033 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULT PATIENTS.
72MCG LINZESS ALLERGAN N202811 Jan. 25, 2017 RX CAPSULE ORAL 9708371 Aug. 16, 2033 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.

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
16158208 PUBCHEM_CID
1307404 RXNORM
192786 MMSL
28804 MMSL
d07902 MMSL
014633 NDDF
703126002 SNOMEDCT_US
703686003 SNOMEDCT_US
C2000261 UMLSCUI
CHEMBL3301676 ChEMBL_ID

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 0456-1202 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