Description

Simple

A medication used to treat constipation associated with irritable bowel syndrome or that has no known cause.

Clinical

A guanylate cyclase-C agonist used to treat constipation associated with irritable bowel syndrome or that is idiopathic in nature.

Overview

Linaclotide is an orally administered, peptide agonist of guanylate cyclase 2C for the treatment of irritable bowel syndrome. Chemically, it is a heterodetic cyclic peptide and consists of fourteen amino acids. The protein sequence is as follows: Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr. There are three disulfide bonds which are located between Cys1 and Cys6; between Cys2 and Cys10; and between Cys5 and Cys13. FDA approved on August 30, 2012.

Pharmacology

Indication

Treatment of irritable bowel syndrome (IBS) with constipation and chronic idiopathic constipation.

Pharmacodynamic

Changes in the appearance and consistency of stools as measured by the Bristol Stool Form Scale (BSFS) have been noted after taking linaclotide.

Mechanism of action

Linaclotide is an agonist of guanylate cyclase-C (GC-C). Once linaclotide and its active metabolite binds to GC-C, it has local effect on the luminal surface of the intestinal epithelium. Activation of GC-C by linaclotide results in the intra- and extracellular increase of cyclic guanosine monophosp... Read more

Absorption

When taken orally, linaclotide is not absorbed into the systemic. No detectable levels of linaclotide or its active metabolite were noted after doses of 125 mcg or 290 mcg were administered.

Protein binding

Information currently not available.

Volume of distribution

Given that linaclotide plasma concentrations following therapeutic oral doses are not measurable, linaclotide is expected to be minimally distributed to tissues.

Clearance

Information currently not available.

Half life

Because linaclotide is not systemically absorbed, half life cannot be calculated.

Route of elimination

Linaclotide is eliminated fecally (3 - 5% as active metabolites). However most of the dose undergoes proteolysis (processes include reduction of disulfide bonds) in the intestine before being excreted via feces.

Toxicity

Most common adverse reactions (incidence of at least 2%) reported in IBS-C or CIC patients are diarrhea, abdominal pain, flatulence and abdominal distension.

Adverse Effects

Contraindications

  • Regions: US
  • Below Age:
    • Amount: 6
    • Unit: year
  • Regions: US
  • Patient Conditions:
      • Name: Gastrointestinal obstruction
      • Drugbank Id: DBCOND0010786

Food Interactions

  • Even when taken with food, linaclotide does not reach detectable levels in the plasma. However, when taken with a high fat meal, one may observe looser stools and a higher stool frequency.

Interactions

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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
Acetazolamide
The risk or severity of adverse effects can be increased when Acetazolamide is combined with Linaclotide.
Aclidinium
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Aclidinium.
Agmatine
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Agmatine.
Alcuronium
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Alcuronium.
Alfentanil
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Alfentanil.
Alloin
The risk or severity of adverse effects can be increased when Linaclotide is combined with Alloin.
Alphacetylmethadol
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Alphacetylmethadol.
Alphaprodine
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Alphaprodine.
Amantadine
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Amantadine.
Amiloride
The risk or severity of adverse effects can be increased when Amiloride is combined with Linaclotide.
Amiodarone
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Amiodarone.
Amitriptyline
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Amitriptyline.
Amlodipine
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Amlodipine.
Amobarbital
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Amobarbital.
Amoxapine
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Amoxapine.
Anisotropine methylbromide
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Anisotropine methylbromide.
Aprobarbital
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Aprobarbital.
Aranidipine
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Aranidipine.
Aripiprazole
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Aripiprazole.
Atracurium
The therapeutic efficacy of Linaclotide can be decreased when used in combination with Atracurium.
1 References
  1. 1 . Busby RW, Kessler MM, Bartolini WP, Bryant AP, Hannig G, Higgins CS, Solinga RM, Tobin JV, Wakefield JD, Kurtz CB, Currie MG: Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. J Pharmacol Exp Ther. 2013 Jan;344(1):196-206. doi: 10.1124/jpet.112.199430. Epub 2012 Oct 22.PubMed: 23090647