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

Effect Regions Age Groups Incidences Evidence Type
Diarrhea US
  • Kind: experimental
    • Percent: 20%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 16%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Abdominal Pain US
  • Kind: experimental
    • Percent: 7%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Abdominal Pain US
  • Kind: experimental
    • Percent: 7%
  • Kind: placebo
    • Percent: 6%
  • Clinical Trial
    Flatulence US
  • Kind: experimental
    • Percent: 6%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Upper Respiratory Tract Infection US
  • Kind: experimental
    • Percent: 5%
  • Kind: placebo
    • Percent: 4%
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 4%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Flatulence US
  • Kind: experimental
    • Percent: 4%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Viral Gastroenteritis US
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Sinusitis US
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Abdominal distension US
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Fecal Incontinence US
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Vomiting US
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Defecation urgency US
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Abdominal distension US
  • Kind: experimental
    • Percent: 2%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Gastroesophagal reflux disease US
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Rectal hemorrhage US
    Post Marketing
    Nausea US
    Post Marketing
    Hematochezia US
    Post Marketing
    Hives US
    Post Marketing
    Allergic Reactions US
    Post Marketing
    Urticaria US
    Post Marketing

    Contraindications

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

    Food Interactions

    Avoid fatty foods. Co-administration with fatty foods may cause loose stools.