[Table], Table 1. Medical Agents for Constipation - PDQ Cancer Information Summaries

Name	Action	Caution/Side Effects	Onset	Selected Drugs/Dosages
Bulk producers	Natural or semisynthetic polysaccharide and cellulose that work with the body’s natural processes to hold water in intestinal tract, soften stool, and increase frequency of stool passage.	To reduce risk of bowel obstruction, take with two 8-oz. (240-mL) glasses of water and maintain adequate hydration.	12–24 h (may be delayed up to 72 h)	Methylcellulose: 2 g dissolved in 8-oz. (240-mL) glass of water PO up to three times daily. Increase as needed by 2 g.
Avoid if fecal impaction or intestinal obstruction is suspected.
Not advised for opioid-induced constipation.	Psyllium: 2.5-30 g PO daily in divided doses.
Saline laxatives	High osmolarity attracts water into lumen of the intestines. Fluid accumulation alters stool consistency, distends bowel, and induces peristaltic movement.	Repeated use can alter fluid and electrolyte balance.	0.5–6 h	Magnesium sulfate: 10–20 g dissolved in 8-oz. (240-mL) glass of water orally. May repeat in 4 h. Do not exceed two doses daily.
Magnesium hydroxide:
	– 400 mg/5 mL liquid: 30–60 mL/day once daily at bedtime or divided.
– 800 mg/5 mL liquid: 15–30 mL/day once daily at bedtime or divided.
– 1,200 mg/5 mL liquid: 10–20 mL/day once daily at bedtime or divided.
Avoid magnesium-containing laxatives in patients with renal dysfunction. Avoid sodium-containing laxatives in patients with edema, congestive heart failure, megacolon, or hypertension.	Magnesium citrate: 195–300 mL as single dose or divided doses over 24 h.
Used to clear bowels for rectal or bowel examination.	Sodium phosphate enemas can cause acute phosphate nephropathy. Cramps may occur.	Sodium phosphate: 4.5-oz. enema as single dose.
Stimulant laxatives	Increase motor activity of bowels by direct action on smooth muscle of the intestine.	Prolonged use causes laxative dependency and loss of normal bowel function.	6–24 h (oral), 0.25-1 h (bisacodyl suppository)	Sennosides: 17.2–34.4 mg PO once or twice daily.
Bisacodyl must be excreted in bile to be active and is not effective with biliary obstruction or diversion. Avoid bisacodyl with known or suspected ulcerative lesions of the colon. May cause cramping.
Used to clear bowels for rectal or bowel examination.	Avoid taking bisacodyl within 1 h of taking antacids, milk, or cimetidine; causes premature dissolving of enteric coating, which results in gastric or duodenal stimulation.	Bisacodyl: 5–15 mg PO once daily or 10-mg suppository once daily.
Lubricant laxatives	Lubricate intestinal mucosa and soften stool to help prevent straining in patients for whom straining would be dangerous.	Give on empty stomach at bedtime. Mineral oil prevents absorption of oil-soluble vitamins and drugs.	6–8 h (oral), 2-15 min (rectal)	Mineral oil (oral):
With older patients, avoid mineral oil due to aspiration potential that can cause lipid pneumonitis.
Can interfere with postoperative healing of anorectal surgery.		– Nonemulsified: 15–45 mL in 24 h.
– Emulsified: 30–90 mL daily as single dose or divided.
Avoid giving with docusate sodium, which causes increased systemic absorption of mineral oil.	Mineral oil (rectal): 118 mL as single dose.
Fecal softeners	Promote water retention, softening stool to prevent straining; most beneficial when stool is hard. Stool softeners and emollient laxatives are of limited use because of colonic resorption of water from the forming stool.	May increase systemic absorption of mineral oil when administered together.	Up to 3 d	Docusate sodium: 50–240 mg taken with full glass of water.
Docusate calcium: 240 mg daily until bowel movement is normal.
Not used as sole regimen but may be useful in combination with stimulant laxatives.	Docusate potassium: 100–300 mg daily until bowel movement is normal; increase daily fluid intake.
Lactulose	Synthetic disaccharide that passes to colon undigested. When broken down in colon, it produces lactic acid, formic acid, acetic acid, and carbon dioxide. These products increase osmotic pressure, increasing amount of water held in stool, which softens stool and increases frequency of passage.	Excessive amounts may cause diarrhea with electrolyte losses.	24–48 h	10–20 g PO daily; may increase to 40 g daily.
Avoid in patients with acute abdomen, fecal impaction, or bowel obstruction.
Polyethylene glycol and electrolytes	Used to clear bowel with minimal water and sodium loss or gain.	Contraindicated in patients with bowel obstruction.	24–96 h	17 g dissolved in 4-8 oz. (120–240 mL) of beverage once daily.
Opioid antagonists	Restricted ability to cross blood-brain barrier.	Give only if other drugs have failed. Contraindicated in patients with bowel obstruction.	In a study of patients with advanced, cancer and other diseases, about 50% of patients defecated within 4 h of receiving the injection.[8,9]	Naloxone: Oral oxycodone: naloxone combination in ratio of 2:1[10]
Methylnaltrexone: Subcutaneous 0.15 mg/kg daily or every other day to treat opioid-induced constipation.
Naldemedine: 0.2 mg PO daily for 2 wk[11]
Block opioid receptors peripherally in the GI tract to reverse opioid-induced decreases in intestinal motility.	Side effects: Dizziness, nausea, abdominal pain, flatulence, diarrhea.	No evidence of withdrawal or other central effects of the opioid; pain scores remained unchanged.	Naloxegol: 12.5–25 mg PO daily
Lubiprostone	Chloride channel activator that acts to increase intestinal fluid secretion and improve fecal transit, bypassing antisecretory effects of opiates.	Contraindicated in patients with bowel obstruction.	24–48 h in chronic constipation.[12]	24 µg PO twice daily (8 µg PO twice daily in IBS).
Dyspnea and chest tightness may occur within 30-60 min of first dose and resolve within a few hours. Syncope and hypotension, some requiring hospitalization, may also occur.
Used for chronic idiopathic constipation, IBS with constipation, and opioid-induced constipation.	Side effects: Diarrhea, nausea, headache, abdominal pain.
Linaclotide	Guanylate cyclase-C agonist that causes increased chloride and bicarbonate secretion into the intestinal lumen, leading to increased intestinal fluid and GI transit.	Contraindicated in patients <2 y and in patients with mechanical GI obstruction.	N/A	145 µg PO daily (72 µg PO daily for tolerability or 290 µg PO daily in IBS).
May cause severe diarrhea associated with syncope, hypertension, and electrolyte abnormalities.
Used for chronic idiopathic constipation, IBS with constipation.	Side effects: Diarrhea, headache, abdominal pain.
Prucalopride	Selective 5-HT4 receptor agonist that stimulates peristaltic reflux and increases intestinal secretions and GI motility.	Contraindicated in patients with intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, or severe inflammatory conditions of the GI tract.	N/A	2 mg PO daily
Used for chronic idiopathic constipation.	Side effects: Diarrhea, nausea, headache, abdominal pain.

Name

Action

Caution/Side Effects

Onset

Selected Drugs/Dosages

Bulk producers

Natural or semisynthetic polysaccharide and cellulose that work with the body’s natural processes to hold water in intestinal tract, soften stool, and increase frequency of stool passage.

To reduce risk of bowel obstruction, take with two 8-oz. (240-mL) glasses of water and maintain adequate hydration.

12–24 h (may be delayed up to 72 h)

Methylcellulose: 2 g dissolved in 8-oz. (240-mL) glass of water PO up to three times daily. Increase as needed by 2 g.

Avoid if fecal impaction or intestinal obstruction is suspected.

Not advised for opioid-induced constipation.

Psyllium: 2.5-30 g PO daily in divided doses.

Saline laxatives

High osmolarity attracts water into lumen of the intestines. Fluid accumulation alters stool consistency, distends bowel, and induces peristaltic movement.

Repeated use can alter fluid and electrolyte balance.

0.5–6 h

Magnesium sulfate: 10–20 g dissolved in 8-oz. (240-mL) glass of water orally. May repeat in 4 h. Do not exceed two doses daily.

Magnesium hydroxide:

– 400 mg/5 mL liquid: 30–60 mL/day once daily at bedtime or divided.

– 800 mg/5 mL liquid: 15–30 mL/day once daily at bedtime or divided.

– 1,200 mg/5 mL liquid: 10–20 mL/day once daily at bedtime or divided.

Avoid magnesium-containing laxatives in patients with renal dysfunction. Avoid sodium-containing laxatives in patients with edema, congestive heart failure, megacolon, or hypertension.

Magnesium citrate: 195–300 mL as single dose or divided doses over 24 h.

Used to clear bowels for rectal or bowel examination.

Sodium phosphate enemas can cause acute phosphate nephropathy. Cramps may occur.

Sodium phosphate: 4.5-oz. enema as single dose.

Stimulant laxatives

Increase motor activity of bowels by direct action on smooth muscle of the intestine.

Prolonged use causes laxative dependency and loss of normal bowel function.

6–24 h (oral), 0.25-1 h (bisacodyl suppository)

Sennosides: 17.2–34.4 mg PO once or twice daily.

Bisacodyl must be excreted in bile to be active and is not effective with biliary obstruction or diversion. Avoid bisacodyl with known or suspected ulcerative lesions of the colon. May cause cramping.

Used to clear bowels for rectal or bowel examination.

Avoid taking bisacodyl within 1 h of taking antacids, milk, or cimetidine; causes premature dissolving of enteric coating, which results in gastric or duodenal stimulation.

Bisacodyl: 5–15 mg PO once daily or 10-mg suppository once daily.

Lubricant laxatives

Lubricate intestinal mucosa and soften stool to help prevent straining in patients for whom straining would be dangerous.

Give on empty stomach at bedtime. Mineral oil prevents absorption of oil-soluble vitamins and drugs.

6–8 h (oral), 2-15 min (rectal)

Mineral oil (oral):

With older patients, avoid mineral oil due to aspiration potential that can cause lipid pneumonitis.

Can interfere with postoperative healing of anorectal surgery.

– Nonemulsified: 15–45 mL in 24 h.

– Emulsified: 30–90 mL daily as single dose or divided.

Avoid giving with docusate sodium, which causes increased systemic absorption of mineral oil.

Mineral oil (rectal): 118 mL as single dose.

Fecal softeners

Promote water retention, softening stool to prevent straining; most beneficial when stool is hard. Stool softeners and emollient laxatives are of limited use because of colonic resorption of water from the forming stool.

May increase systemic absorption of mineral oil when administered together.

Up to 3 d

Docusate sodium: 50–240 mg taken with full glass of water.

Docusate calcium: 240 mg daily until bowel movement is normal.

Not used as sole regimen but may be useful in combination with stimulant laxatives.

Docusate potassium: 100–300 mg daily until bowel movement is normal; increase daily fluid intake.

Lactulose

Synthetic disaccharide that passes to colon undigested. When broken down in colon, it produces lactic acid, formic acid, acetic acid, and carbon dioxide. These products increase osmotic pressure, increasing amount of water held in stool, which softens stool and increases frequency of passage.

Excessive amounts may cause diarrhea with electrolyte losses.

24–48 h

10–20 g PO daily; may increase to 40 g daily.

Avoid in patients with acute abdomen, fecal impaction, or bowel obstruction.

Polyethylene glycol and electrolytes

Used to clear bowel with minimal water and sodium loss or gain.

Contraindicated in patients with bowel obstruction.

24–96 h

17 g dissolved in 4-8 oz. (120–240 mL) of beverage once daily.

Opioid antagonists

Restricted ability to cross blood-brain barrier.

Give only if other drugs have failed. Contraindicated in patients with bowel obstruction.

In a study of patients with advanced, cancer and other diseases, about 50% of patients defecated within 4 h of receiving the injection.[8,9]

Naloxone: Oral oxycodone: naloxone combination in ratio of 2:1[10]

Methylnaltrexone: Subcutaneous 0.15 mg/kg daily or every other day to treat opioid-induced constipation.

Naldemedine: 0.2 mg PO daily for 2 wk[11]

Block opioid receptors peripherally in the GI tract to reverse opioid-induced decreases in intestinal motility.

Side effects: Dizziness, nausea, abdominal pain, flatulence, diarrhea.

No evidence of withdrawal or other central effects of the opioid; pain scores remained unchanged.

Naloxegol: 12.5–25 mg PO daily

Lubiprostone

Chloride channel activator that acts to increase intestinal fluid secretion and improve fecal transit, bypassing antisecretory effects of opiates.

Contraindicated in patients with bowel obstruction.

24–48 h in chronic constipation.[12]

24 µg PO twice daily (8 µg PO twice daily in IBS).

Dyspnea and chest tightness may occur within 30-60 min of first dose and resolve within a few hours. Syncope and hypotension, some requiring hospitalization, may also occur.

Used for chronic idiopathic constipation, IBS with constipation, and opioid-induced constipation.

Side effects: Diarrhea, nausea, headache, abdominal pain.

Linaclotide

Guanylate cyclase-C agonist that causes increased chloride and bicarbonate secretion into the intestinal lumen, leading to increased intestinal fluid and GI transit.

Contraindicated in patients <2 y and in patients with mechanical GI obstruction.

N/A

145 µg PO daily (72 µg PO daily for tolerability or 290 µg PO daily in IBS).

May cause severe diarrhea associated with syncope, hypertension, and electrolyte abnormalities.

Used for chronic idiopathic constipation, IBS with constipation.

Side effects: Diarrhea, headache, abdominal pain.

Prucalopride

Selective 5-HT4 receptor agonist that stimulates peristaltic reflux and increases intestinal secretions and GI motility.

Contraindicated in patients with intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, or severe inflammatory conditions of the GI tract.

N/A

2 mg PO daily

Used for chronic idiopathic constipation.

Side effects: Diarrhea, nausea, headache, abdominal pain.

From: Gastrointestinal Complications (PDQ®)

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