linaclotide 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

None

Approvals:

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

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
Constipation 122.95 13.28 211 18195 280184 90329857
Diarrhoea 111.03 13.28 429 17977 938761 89671280
Product dose omission issue 100.69 13.28 198 18208 291489 90318552
Abdominal distension 71.76 13.28 109 18297 130492 90479549
Product dispensing error 52.19 13.28 32 18374 12241 90597800
Surgery 51.23 13.28 54 18352 44833 90565208
Glossodynia 50.28 13.28 4 18402 321775 90288266
Illness 50.17 13.28 72 18334 81897 90528144
Systemic lupus erythematosus 50.16 13.28 7 18399 361889 90248152
General physical health deterioration 46.64 13.28 8 18398 355107 90254934
Infusion related reaction 42.12 13.28 16 18390 416764 90193277
Headache 41.44 13.28 308 18098 862438 89747603
Maternal exposure during pregnancy 39.54 13.28 12 18394 360051 90249990
Product administration interrupted 39.40 13.28 27 18379 12465 90597576
Wound 39.40 13.28 7 18399 302973 90307068
Incorrect dose administered 39.32 13.28 63 18343 78867 90531174
Anal incontinence 37.38 13.28 29 18377 16201 90593840
Product packaging quantity issue 35.27 13.28 13 18393 1589 90608452
Inappropriate schedule of product administration 34.87 13.28 87 18319 149846 90460195
Arthropathy 33.89 13.28 16 18390 366226 90243815
Abdominal pain 33.53 13.28 164 18242 395557 90214484
Treatment failure 31.82 13.28 11 18395 303917 90306124
Completed suicide 31.48 13.28 82 18324 144976 90465065
Thyroid atrophy 30.67 13.28 8 18398 308 90609733
Product physical issue 29.95 13.28 17 18389 5643 90604398
Contraindicated product administered 29.59 13.28 14 18392 320125 90289916
Impaired healing 29.19 13.28 6 18400 234193 90375848
Drug intolerance 28.88 13.28 29 18377 447562 90162479
Product storage error 27.95 13.28 27 18379 20214 90589827
Feeling abnormal 27.94 13.28 86 18320 167149 90442892
Flatulence 27.78 13.28 38 18368 41329 90568712
Pre-existing condition improved 27.00 13.28 19 18387 9150 90600891
Dysphagia 27.00 13.28 66 18340 112212 90497829
Nausea 26.74 13.28 343 18063 1109973 89500068
COVID-19 26.52 13.28 85 18321 168758 90441283
Migraine 26.49 13.28 92 18314 190300 90419741
Lower respiratory tract infection 26.36 13.28 9 18397 250650 90359391
Exposure during pregnancy 26.06 13.28 8 18398 238402 90371639
Joint swelling 25.75 13.28 39 18367 503261 90106780
Impaired gastric emptying 25.47 13.28 21 18385 12788 90597253
Hepatic enzyme increased 24.87 13.28 22 18384 360714 90249327
Rheumatoid arthritis 23.95 13.28 23 18383 362591 90247450
Malabsorption 23.30 13.28 14 18392 5164 90604877
Anxiety 22.48 13.28 123 18283 309649 90300392
Cervical radiculopathy 22.37 13.28 9 18397 1393 90608648
Type 2 diabetes mellitus 21.89 13.28 7 18399 203237 90406804
Volvulus 21.52 13.28 10 18396 2193 90607848
Dermatitis atopic 21.21 13.28 25 18381 23447 90586594
Thrombocytopenia 21.08 13.28 8 18398 208717 90401324
Stress 20.80 13.28 49 18357 81346 90528695
Ill-defined disorder 20.57 13.28 6 18400 184885 90425156
Lymph node pain 20.29 13.28 9 18397 1772 90608269
Haemorrhoids 20.19 13.28 26 18380 26676 90583365
Insurance issue 19.80 13.28 17 18389 10941 90599100
Swelling 19.08 13.28 35 18371 419023 90191018
Intestinal obstruction 18.98 13.28 30 18376 37101 90572940
Vitamin B12 deficiency 18.61 13.28 14 18392 7472 90602569
Blood potassium decreased 18.38 13.28 34 18372 47693 90562348
Neutropenia 17.67 13.28 12 18394 224892 90385149
Therapy interrupted 17.21 13.28 34 18372 50074 90559967
Cardiac arrest 16.62 13.28 53 18353 104882 90505159
Intervertebral disc compression 16.50 13.28 7 18399 1238 90608803
Blood cholesterol increased 16.47 13.28 11 18395 208001 90402040
Feeding disorder 16.40 13.28 19 18387 17493 90592548
Oropharyngeal pain 16.30 13.28 56 18350 115131 90494910
Multiple sclerosis relapse 16.19 13.28 34 18372 52271 90557770
Febrile neutropenia 16.10 13.28 6 18400 158343 90451698
Therapeutic response unexpected 16.07 13.28 21 18385 21859 90588182
Subacute hepatic failure 16.05 13.28 4 18402 128 90609913
Panic attack 15.89 13.28 23 18383 26342 90583699
Bowel movement irregularity 15.79 13.28 12 18394 6502 90603539
Faeces hard 15.20 13.28 9 18397 3233 90606808
Accidental exposure to product 14.85 13.28 29 18377 42337 90567704
Blister 14.80 13.28 18 18388 254980 90355061
Dehydration 14.62 13.28 78 18328 194369 90415672
Exposure via skin contact 14.25 13.28 14 18392 10691 90599350
Oesophageal hypomotility 14.21 13.28 4 18402 206 90609835
Nervousness 14.05 13.28 25 18381 34031 90576010

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 96.27 21.01 154 3518 460695 42156968
Prescribed underdose 40.18 21.01 19 3653 10263 42607400
Off label use 35.87 21.01 128 3544 638207 41979456
Inappropriate schedule of product administration 34.71 21.01 42 3630 95860 42521803
Constipation 31.81 21.01 53 3619 162238 42455425
Death 25.07 21.01 93 3579 471092 42146571
Drug ineffective 24.60 21.01 113 3559 630084 41987579
Urinary retention 21.28 21.01 22 3650 42192 42575471

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
Constipation 104.63 13.55 191 16527 357595 110214986
Product dose omission issue 85.58 13.55 165 16553 321617 110250964
Diarrhoea 73.51 13.55 353 16365 1139152 109433429
Headache 48.76 13.55 262 16456 882115 109690466
Abdominal distension 46.73 13.55 90 16628 175013 110397568
General physical health deterioration 35.77 13.55 10 16708 425285 110147296
Completed suicide 35.17 13.55 98 16620 242283 110330298
Incorrect dose administered 34.95 13.55 59 16659 103582 110468999
Nausea 33.77 13.55 309 16409 1235381 109337200
Surgery 33.35 13.55 36 16682 41247 110531334
Thyroid atrophy 33.25 13.55 8 16710 299 110572282
Inappropriate schedule of product administration 27.26 13.55 80 16638 203557 110369024
Illness 26.68 13.55 46 16672 82125 110490456
Abdominal pain 26.67 13.55 150 16568 512839 110059742
Systemic lupus erythematosus 25.43 13.55 4 16714 254334 110318247
Treatment failure 24.29 13.55 6 16712 277228 110295353
Febrile neutropenia 23.89 13.55 9 16709 316758 110255823
Product administration interrupted 23.79 13.55 17 16701 11275 110561306
Dermatitis atopic 23.72 13.55 24 16694 25517 110547064
Pain 23.14 13.55 233 16485 954722 109617859
Neutropenia 23.12 13.55 14 16704 374606 110197975
Anal incontinence 22.93 13.55 22 16696 21942 110550639
Lymph node pain 22.28 13.55 9 16709 1893 110570688
Acute kidney injury 22.00 13.55 39 16679 635391 109937190
Oropharyngeal pain 21.92 13.55 57 16661 135219 110437362
Malabsorption 21.70 13.55 13 16705 6412 110566169
Impaired gastric emptying 21.34 13.55 17 16701 13258 110559323
Dysphagia 21.18 13.55 61 16657 153539 110419042
Infusion related reaction 21.17 13.55 16 16702 381146 110191435
COVID-19 21.06 13.55 83 16635 244977 110327604
Urinary tract infection 20.79 13.55 101 16617 326181 110246400
Dizziness 20.21 13.55 177 16541 698016 109874565
Anxiety 19.31 13.55 103 16615 344975 110227606
Glossodynia 19.07 13.55 5 16713 221999 110350582
Accidental exposure to product 18.93 13.55 30 16688 49978 110522603
Wound 18.81 13.55 6 16712 234431 110338150
Maternal exposure during pregnancy 17.98 13.55 8 16710 254875 110317706
Feeling abnormal 17.84 13.55 64 16654 180647 110391934
Intervertebral disc compression 17.72 13.55 7 16711 1390 110571191
Thrombocytopenia 17.70 13.55 16 16702 348869 110223712
Multiple sclerosis relapse 17.46 13.55 29 16689 50211 110522370
Exposure via skin contact 17.31 13.55 15 16703 13132 110559449
Haemorrhoids 17.24 13.55 24 16694 35648 110536933
Flatulence 16.67 13.55 29 16689 52120 110520461
Lower respiratory tract infection 16.58 13.55 8 16710 243098 110329483
Oesophageal hypomotility 16.56 13.55 4 16714 152 110572429
Cervical radiculopathy 16.50 13.55 7 16711 1667 110570914
Fall 16.43 13.55 151 16567 603331 109969250
Gastrooesophageal reflux disease 16.31 13.55 62 16656 179914 110392667
Exposure during pregnancy 15.93 13.55 3 16715 167421 110405160
Impaired healing 15.84 13.55 5 16713 196712 110375869
Malaise 15.79 13.55 163 16555 671656 109900925
Migraine 15.45 13.55 59 16659 171593 110400988
Dihydrotestosterone increased 15.27 13.55 3 16715 42 110572539
Nervousness 15.19 13.55 23 16695 36828 110535753
Arthropathy 14.80 13.55 13 16705 287509 110285072
Palpitations 14.55 13.55 55 16663 159157 110413424
Hospitalisation 14.52 13.55 51 16667 142442 110430139
Contraindicated product administered 14.33 13.55 10 16708 248257 110324324
Volvulus 14.22 13.55 8 16710 3510 110569071
Fatigue 14.15 13.55 260 16458 1215698 109356883
Intervertebral disc protrusion 13.93 13.55 19 16699 27679 110544902
Therapy interrupted 13.76 13.55 26 16692 49796 110522785

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 D000074268 Guanylyl Cyclase C Agonists
MeSH PA D005765 Gastrointestinal Agents
MeSH PA D020536 Enzyme Activators
FDA MoA N0000185499 Guanylate Cyclase Activators
FDA EPC N0000185500 Guanylate Cyclase-C Agonist
CHEBI has role CHEBI:68553 guanylate cyclase 2C agonist
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50503 laxative
CHEBI has role CHEBI:53784 antispasmodic drug

Related Drugs by ATC class:

A06AX Other drugs for constipation 7 drugs
elobixibatglycerollubiprostoneplecanatideprucalopridetegaserodtenapanor

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 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
145MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 7304036 Aug. 30, 2026 METHOD OF TREATING OF IRRITABLE BOWEL SYNDROME WITH CONSTIPATION (IBS-C) IN PEDIATRIC PATIENTS 7 YEARS OF AGE AND OLDER
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
145MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 8933030 Feb. 17, 2031 METHOD OF TREATING OF IRRITABLE BOWEL SYNDROME WITH CONSTIPATION (IBS-C) IN PEDIATRIC PATIENTS 7 YEARS OF AGE AND OLDER
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.
145MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 8748573 Oct. 30, 2031 METHOD OF TREATING OF IRRITABLE BOWEL SYNDROME WITH CONSTIPATION (IBS-C) IN PEDIATRIC PATIENTS 7 YEARS OF AGE AND OLDER
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.
145MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL 9708371 Aug. 16, 2033 METHOD OF TREATING OF IRRITABLE BOWEL SYNDROME WITH CONSTIPATION (IBS-C) IN PEDIATRIC PATIENTS 7 YEARS OF AGE AND OLDER
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)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
145MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL June 12, 2026 TREATMENT OF FUNCTIONAL CONSTIPATION IN PEDIATRIC PATIENTS 6 TO 17 YEARS OF AGE
72MCG LINZESS ABBVIE N202811 Jan. 25, 2017 RX CAPSULE ORAL June 12, 2026 TREATMENT OF FUNCTIONAL CONSTIPATION IN PEDIATRIC PATIENTS 6 TO 17 YEARS OF AGE
145MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL Nov. 4, 2028 NEW PATIENT POPULATION
145MCG LINZESS ABBVIE N202811 Aug. 30, 2012 RX CAPSULE ORAL May 4, 2029 PEDIATRIC EXCLUSIVITY
72MCG LINZESS ABBVIE N202811 Jan. 25, 2017 RX CAPSULE ORAL May 21, 2029 NEW PATIENT POPULATION

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
CHEMBL3301675 ChEMBL_ID
C523483 MESH_SUPPLEMENTAL_RECORD_UI
5017 IUPHAR_LIGAND_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
CHEBI:68551 CHEBI
CHEMBL3301676 ChEMBL_ID
8802 INN_ID
16158208 PUBCHEM_CID
N0TXR0XR5X INXIGHT DRUGS

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