Linaclotide
Indications
Linaclotide is used for:
Irritable Bowel Syndrome, Chronic Idiopathic Constipation
Adult Dose
Irritable Bowel Syndrome
Indicated in adults for irritable bowel syndrome with constipation
290 mcg PO qDay on empty stomach; administer at least 30 minutes before first meal of the day
Chronic Idiopathic Constipation
Indicated for adults with chronic idiopathic constipation
Recommended dose: 145 mcg PO qDay
72 mcg PO qDay may be used based on individual presentation
Child Dose
<6 years: Contraindicated
6-17 years: Safety and efficacy not established (see Black Box Warnings and Cautions)
Renal Dose
Administration
Take on an empty stomach; administer at least 30 minutes before first meal of the day
Contra Indications
Hypersensitivity. Patients w/ known or suspected mechanical GI obstruction.
Precautions
Rule out organic diseases & establish diagnosis of moderate to severe IBS-C before use. Discontinue in prolonged (eg, >1 wk) or severe diarrhoea until resolved. Control electrolyte if prone to disturbance of water or electrolyte balance (eg, elderly, CV diseases, diabetes, HTN). Not recommended in chronic intestinal tract inflammatory conditions (eg, Crohn's disease & ulcerative colitis). Pregnancy & lactation. Elderly >65 yr.
Pregnancy-Lactation
Pregnancy Category: C
Lactation: Unknown whether distributed in breast milk; however, linaclotide and its active metabolite are not measurable in plasma following administration of the recommended clinical doses
Interactions
Increased risk of diarrhoea w/ proton pump inhibitors, laxatives or NSAIDs. May reduce the efficacy of OCs & medicinal products absorbed in the intestinal tract w/ a narrow therapeutic index (eg, levothyroxine).
Adverse Effects
Side effects of Linaclotide :
>10%
Diarrhea (16-20%)
1-10%
Abdominal pain (7%)
Flatulence (4-6%)
URI (<2-5%)
Headache (<2-4%)
Viral gastroenteritis (<2-3%)
Sinusitis (<2-3%)
Abdominal distension (2-3%)
Severe diarrhea (2%)
Dyspepsia (1-<2%)
Fecal incontinence (1-<2%)
Viral gastroenteritis (1-<2%)
GERD (1-<2%)
Vomiting (1-<2%)
Fatigue (1-<2%)
Mechanism of Action
Guanylate cyclase C (GC-C) agonist; activation of GC-C located on the luminal surface of intestinal epithelial cells leads to increased cyclic guanosine monophosphate (cGMP), anion secretion, fluid secretion, and intestinal transit
Appears to work topically rather than systemically; 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