Pharmacological Management of Chronic Idiopathic Constipation

Publication Date: May 19, 2023

Fiber

Recommendation 1

In adults with CIC, the panel suggests the use of fiber supplementation over management without fiber supplements. (C, L)
Implementation considerations:a
  • Dietary assessment is important to determine total fiber intake from diet and supplements
  • 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
620

Osmotic laxatives

Recommendation 2

In adults with CIC, the panel recommends the use of PEG compared with management without PEG. (S, M)
Implementation considerations:a
  • A trial of fiber supplement can be considered for mild constipation before PEG use or in combination with PEG
  • Response to PEG has been shown to be durable over 6 mo
  • Side effects include abdominal distension, loose stool, flatulence, and nausea
620

Recommendation 3

In adults with CIC, the panel suggests the use of magnesium oxide over management without magnesium oxide. (C, VL)
Implementation considerations:a
  • The trials were conducted for 4 wk, although longer term use is probably appropriate
  • The panel suggests starting at a lower dose, which may be increased if necessary
  • Avoid use in patients with renal insufficiency due to risk of hypermagnesemia
620

Recommendation 4

In adults with CIC who fail or are intolerant to OTC therapies, the panel suggests the use of lactulose over management without lactulose. (C, VL)
Implementation considerations:a
  • Bloating and flatulence are dose-dependent and common side effects, which may limit its use in clinical practice
620

Stimulant laxatives

Recommendation 5

In adults with CIC, the panel recommends the use of bisacodyl or sodium picosulphate short term or as rescue therapy over management without bisacodyl or sodium picosulphate. (S, M)
Implementation considerations:a
  • Short-term use is defined as daily use for 4 wk or less. While long-term use is probably appropriate, data are needed to better understand tolerance and side effects
  • This is a good option for occasional use or rescue therapy in combination with other pharmacological agents for CIC
  • The most common side effects are abdominal pain, cramping and diarrhea. The panel suggests starting at a lower dose and increasing the dose as tolerated
620

Recommendation 6

In adults with CIC, the panel suggests the use of senna over management without senna. (C, L)
Implementation considerations:a
  • While the trials were conducted for 4 wk, longer term use is probably appropriate, but data are needed to better understand tolerance and side effects
  • The dose evaluated in trials is higher than commonly used doses in practice. The panel suggests starting at lower dose and increase if no response
  • Abdominal pain and cramping may occur with a higher dose of senna
620

Secretagogues

Recommendation 7

In adults with CIC who do not respond to OTC agents, the panel suggests the use of lubiprostone over management without lubiprostone. (C, L)
Implementation considerations:a
  • Can be used as a replacement or as an adjunct to OTC agents
  • Duration of treatment in trials was 4 wk, but the drug label does not provide a limit
  • Nausea may occur; however, the risk of nausea is dose-dependent and seems to be lower when taken with food and water
620

Recommendation 8

In adults with CIC who do not respond to OTC agents, the panel recommends the use of linaclotide over management without linaclotide. (S, M)
Implementation considerations:a
  • Can be used as a replacement or as an adjunct to OTC agents
  • Duration of treatment in trials was 12 wk but the drug label does not provide a limit
  • May be associated with side effects of diarrhea leading to discontinuation of treatment
620

Recommendation 9

In adults with CIC who do not respond to OTC agents, the panel recommends the use of plecanatide over management without plecanatide. (S, M)
Implementation considerations:a
  • Can be used as a replacement or as an adjunct to OTC agents
  • Duration of treatment in trials was 12 wk, but the drug label does not provide a limit
  • May be associated with side effects of diarrhea leading to discontinuation of treatment
620

Serotonin type 4 (5-HT4) Agonist

Recommendation 10

In adults with CIC who do not respond to OTC agents, the panel recommends the use of prucalopride over management without prucalopride. (S, M)
Implementation considerations:a
  • Duration of treatment in trials was 4–24 wk but the drug label does not provide a limit
  • Can be used as a replacement or as an adjunct to OTC agents
  • May be associated with side effects of headache, abdominal pain, nausea, and diarrhea
620

a The implementation considerations are based on the collective experience of the panel members, and evidence may not be available for each of the Implementation considerations.

Table

Table 1. Overview of Interventions for the Pharmacological Management of Chronic Idiopathic Constipation

What medications can be used to treat chronic idiopathic constipation? Mechanism of action Recommended initial dose Guidance for dose titration Maximum dose Estimated monthly cost, USDa Additional comments
Fiber Soluble fiber traps water in the intestine and softens stool

Insoluble fiber increases stool bulk
Starting dose of 5 g daily

The Academy of Nutrition and Dietetics recommends 14 g/ 1,000 kcal intake per day

Total daily fiber intake (dietary + supplement) 20–30 g/d
Per response to symptoms and side effects

Common side effects include bloating and abdominal discomfort
Usually no benefit to increasing total fiber intake over 25–30 g <$50 Ensure adequate hydration as fiber intake increases

No clear evidence that soluble or insoluble fiber is more effective

Soluble fiber includes psyllium, inulin, oats, fruit, barley, and legumes

Insoluble fiber includes wheat bran, methylcellulose, wheat, rye, and other grains
Polyethylene glycol Osmotic laxative 17 g daily Per symptom response and side effects

Common side effects include bloating, abdominal discomfort, and cramping
No clear maximum
dose
$10–$45 Response to PEG has been shown to be durable over 6 mo
Magnesium oxide Osmotic laxative 400–500 mg daily Per symptom and response and side effects No clear maximum dose

Prior studies used 1,000–1,500 mg daily
<$50 Use with caution in patients with renal insufficiency and in pregnancy
Lactulose Osmotic laxative 15 g daily Per symptom response and side effects

Bloating and flatulence may be limiting if preexisting symptoms or at higher doses
No clear maximum dose

May cause hypernatremia and hypokalemia if patients experience significant diarrhea
<$50 Only osmotic agent studied in pregnancy
Bisadocyl and picosulfate Stimulant laxative Bisacodyl 5 mg daily Per symptom response and side effects

Side effects limited by cramping and abdominal discomfort
10 mg orally daily <$50 Recommended for short-term use or rescue therapy

Prolonged or excessive use can cause diarrhea and electrolyte imbalance

Long-term safety and efficacy unknown
Senna Stimulant laxative 8.6–17.2 mg daily Per symptom response and side effects

Side effects commonly reported include cramping and abdominal discomfort
Maximum recommended dose is 4 tablets twice daily <$50 Also present in many laxative teas, where dose may be difficult to calculate

Long-term safety and efficacy unknown
Lubiprostone Intestinal secretagogue acting on chloride channel type 2 in the gut to increase chloride secretion 24 μg twice a day (BID) Per symptom response

Diarrhea may
occur in a subset of patients, leading to discontinuation
24 μg BID $374 May have benefit for abdominal pain

Also approved for the
treatment of irritable bowel syndrome with constipation (IBS-C) at a dose of 8 μg BID
Linaclotide Intestinal secretagogue acting on guanylate cyclase-C, which activates CFTR in the gut to increase chloride secretion 72–145 μg daily Per symptom response

Diarrhea may occur in a subset of patients, leading to discontinuation
290 μg daily $523 May have benefit for abdominal pain

Also approved for the treatment of IBS-C at a dose of 290 ug daily
Plecanatide Intestinal secretagogue acting on guanylate cyclase-C, which activates CFTR in the gut to increase chloride secretion 3 mg daily Per symptom response

Diarrhea may occur in a subset of patients, leading to discontinuation
3 mg daily $526 May have benefit for abdominal pain.

Also approved for the treatment of IBS-C at a dose of 3 mg daily
Prucalopride 5-HT4 agonist that stimulates colonic peristalsis, which increases bowel motility 1–2 mg daily Per symptom response

Headaches and
diarrhea may occur in a subset of patients, leading to discontinuation
2 mg daily $563 May have additional benefit for abdominal pain

5-HT4, serotonin type 4; BID, twice a day; IBS-C, irritable bowel syndrome with constipation; PEG, polyethylene glycol; USD, US dollar.
aThe given cost accommodates the extent of generic and prescription medications and may not be the exact cost. In addition, the given cost is not the cost-effectiveness of the medication, but a probable cost per month.

Recommendation Grading

Abbreviations

  • ACG: American College Of Gastroenterology
  • AGA: American Gastroenterological Association
  • CIC: Chronic Idiopathic Constipation
  • OTC: Over The Counter
  • PEG: Polyethylene Glycol

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Pharmacological Management of Chronic Idiopathic Constipation

Authoring Organizations

Publication Month/Year

May 19, 2023

Supplemental Implementation Tools

Document Type

Guideline

Country of Publication

US

Document Objectives

Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults.

Target Patient Population

The patient population of interest was adults (18 years or older) diagnosed with chronic idiopathic constipation

Target Provider Population

Gastroenterologists, primary care providers and other allied healthcare professionals caring for patients with CIC

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Treatment, Management

Diseases/Conditions (MeSH)

D003248 - Constipation

Keywords

constipation, chronic constipation, CIC, chronic idiopathic constipation

Source Citation

Chang, Lin MD, AGAF, FACG1,*; Chey, William D. MD, FACG2,*; Imdad, Aamer MBBS, MPH3,*; Almario, Christopher V. MD, MSHPM, FACG4; Bharucha, Adil E. MD5; Diem, Susan MD, MPH6,7; Greer, Katarina B. MD, MS Epi8,9; Hanson, Brian MD6,10; Harris, Lucinda A. MD, FACG11; Ko, Cynthia MD12; Murad, M. Hassan MD13; Patel, Amit MD, FACG14; Shah, Eric D. MD, MBA, FACG2,15; Lembo, Anthony J. MD, FACG16,†; Sultan, Shahnaz MD, MHSc, FACG6,17,†. American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation. The American Journal of Gastroenterology ():10.14309/ajg.0000000000002227, May 19, 2023. | DOI: 10.14309/ajg.0000000000002227 

Supplemental Methodology Resources

Data Supplement

Methodology

Number of Source Documents
90
Literature Search Start Date
May 15, 2021
Literature Search End Date
November 5, 2022