AGA/ACG Constipation Management Clinical Guidelines
American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation
Summary:
Chronic idiopathic constipation (CIC) is a common clinical diagnosis that affects approximately 8%–12% of the US population. The American Gastroenterological Association (AGA) and American College of Gastroenterology (ACG) jointly developed clinical guidelines to provide evidence-based recommendations for the pharmacological management of CIC in adults. Nonpharmacological therapies often represent the initial steps in management and may include dietary recommendations e.g. increased fluid intake and dietary faiber and behavioral changes e.g. exercise. The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults.
KEY POINTS:
Fiber
- Fiber supplements can be used as first-line therapy for CIC, particularly for individuals with low dietary fiber intake.
- Among the evaluated fiber supplements, only psyllium appears to be effective (with very limited and uncertain data on bran and inulin).
- Adequate hydration should be encouraged with the use of fiber.
- Flatulence is a commonly observed side effect with the use of fiber.
Osmotic Laxatives
- Polyethylene Glycol (PEG)
- PEG is a long-chain polymer of ethylene oxide, which acts as an osmotic laxative
- PEG is approved at a dose of 17 g daily for the treatment of occasional constipation by the FDA
- Trial of fiber supplement can be considered for mild constipation before PEG use
- Several studies show PEG likely results in greater response to constipation compared to placebo
- Side effects include abdominal distension, loose stool, flatulence, and nausea
- Magnesium Oxide
- Magnesium is a naturally occurring element and within the lumen of the GI tract, non-absorbed magnesium creates an osmotic gradient, which leads to net secretion of water and electrolytes, which can exert a beneficial effect on constipation-related symptoms.
- Several studies show magnesium oxide likely results in greater response to constipation compared to placebo
- Start a lower dose (500 mg/d) and increase as necessary to avoid side effects of diarrhea, nausea
- Avoid use in patients with renal insufficiency due to risk of hypermagnesemia.
- Lactulose
- Lactulose is b-galactosido-fructose, a synthetic disaccharide not digested in the small intestine that exerts an osmotic laxative effect in the colon to promote peristalsis.
- Based on limited studies, lactulose may have little to no effect on soft bowel movements
- Bloating and flatulence are dose-dependent and common side effects, which may limit its use in clinical practice.
Stimulant Laxatives
- Bisacodyl or sodium picosulfate
- Bisacodyl and SPS are converted in the gut into the same active metabolite, bis-(phydroxyphenyl)-pyridyl-2-methane (BHPM). Bisacodyl is converted into BHPM by small bowel and colonic mucosal deacetylase enzymes while SPS is converted into BHPM by colonic bacteria desulfate enzymes. BHPM acts directly on the colonic mucosa to stimulate colonic peristalsis and secretion
- Use bisacodyl or sodium picosulfate short term (<4 weeks) or as rescue therapy
- Based on meta-analyzed data from 2 studies, SPS likely leads to a large increase in soft bowel movements per week
- The most common side effects are abdominal pain, cramping and diarrhea.
- Senna
- Senna is a natural derivative of the senna plant. Sennosides A and B are sequentially metabolized by the gut microbiota to the active metabolites, rheinanthrone and rhein, which stimulate the production of prostaglandin E2 and secretion of chloride ions leading to attendant changes in colonic peristalsis and luminal water content
- Use senna for short term (<4 weeks)
- Limited evidence shows patients treated with senna may have higher soft bowel movements per week compared to placebo
- Side effects include abdominal pain, cramping, diarrhea
Secratogues
- Lubiprostone
- Lubiprostone, a bicyclic fatty acid derived from prostaglandin E1 that increases intestinal chloride secretion by activating type 2 chloride channels on epithelial cells, is approved by FDA for treating CIC at a dose of 24 ug 2 times daily.
- The studied dose of lubiprostone was given for 4 weeks
- Can be used as a replacement or as an adjunct to over-the-counter agents
- Increased risk of nausea and diarrhea
- Plecanatide
- Plecanatide is a pH-dependent guanylate cyclase-C agonist approved by the FDA for CIC at a dose of 3 mg daily taken with or without food.
- In adults with CIC who do not respond to over-the-counter agents, panel recommends the use of plecanatide over management without
- Duration of treatment in trials was 4–24 weeks, though label has no limit
- May be associated with side effects of headache, abdominal pain, nausea, and diarrhea
5-HT4-Agonist
- Prucalopride
- Selective agonist of serotonin 5 HT-4 receptors that promotes neurotransmission by the enteric neurons resulting in stimulation of the peristaltic reflex, intestinal secretions, and GI motility
- In adults with CIC who do not respond to OTC agents, the panel recommends the use of prucalopride over management without prucalopride
- Recommended dose 2 mg or 1 mg if CrCl < 30 ml/min
- Can be used as a replacement or adjunct for OTC agents
- May be associated with side effects of headache, abdominal pain, nausea, and diarrhea
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