What are the first‑line and second‑line treatments for constipation?

First and Second Line Treatment for Constipation

Direct Answer

Start with polyethylene glycol (PEG) 17g daily as first-line therapy for constipation, and add stimulant laxatives (senna or bisacodyl) as second-line or rescue therapy if PEG alone is insufficient. 1, 2

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First-Line Treatment: Osmotic Laxatives

Polyethylene glycol (PEG) is the gold-standard first-line pharmacological treatment for chronic constipation. 1, 2, 3

• Dosing: PEG 17g once daily, dissolved in 4-8 ounces of water, juice, or coffee 1, 2
• Mechanism: Works by sequestering fluid in the bowel through osmotic action, increasing water content in the large intestine 2
• Advantages: Minimal systemic absorption makes it the safest option across most patient populations, including those with renal impairment, pregnancy, and elderly patients 1, 2
• Alternative osmotic agent: Lactulose 15g daily can be used as an alternative, particularly in renal patients where it may provide additional renoprotective effects 1

Why Not Fiber First?

While dietary fiber supplementation is often recommended, osmotic laxatives like PEG are superior to bulk-forming agents (psyllium, methylcellulose) for most patients with constipation. 2

• Bulk-forming agents require adequate fluid intake (at least 8 oz per dose) and mobility to prevent bowel obstruction 1, 2
• Fiber supplements are contraindicated in opioid-induced constipation and should be avoided in patients with fluid restrictions or limited mobility 1, 2
• The evidence supporting fiber is weaker compared to osmotic laxatives 2, 3

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Second-Line Treatment: Stimulant Laxatives

If PEG alone provides inadequate response, add stimulant laxatives (senna or bisacodyl) to the regimen. 1, 2

• Mechanism: Stimulate intestinal motility and peristalsis 4
• Usage: Can be used as rescue therapy or scheduled if osmotic laxatives are insufficient 2, 3
• Forms: Bisacodyl is available as tablets or suppositories for flexible administration 4

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Treatment Algorithm

1. Start with PEG 17g once daily mixed in 8 oz liquid, ensuring adequate fluid intake 1, 2
2. Titrate PEG dose based on response, with the goal of achieving one non-forced bowel movement every 1-2 days 4
3. If inadequate response after appropriate trial, add stimulant laxative (senna or bisacodyl) 2
4. Review efficacy after 3 months and discontinue if no response 4
5. If constipation persists despite combination therapy, reassess for bowel obstruction, hypercalcemia, or medication causes before escalating to third-line agents 4

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Critical Safety Considerations and Pitfalls

Absolute Contraindications

• Never use magnesium-containing products (magnesium hydroxide, magnesium sulfate, milk of magnesia) in patients with any degree of renal impairment due to life-threatening hypermagnesemia risk 1, 2
• Avoid sodium phosphate enemas in renal dysfunction and limit to maximum once daily if used 4
• Avoid rectal suppositories or enemas in patients with neutropenia, thrombocytopenia, recent colorectal surgery, or severe colitis 1, 2

Common Pitfalls to Avoid

• Do not prescribe docusate (stool softener) – multiple trials show no benefit, and it is not recommended 4, 2
• Do not assume fiber supplements will help – they worsen symptoms in patients with fluid restrictions and are contraindicated in opioid-induced constipation 1, 2
• Do not use bulk-forming laxatives in non-ambulatory patients with low fluid intake due to mechanical obstruction risk 2
• Always prescribe prophylactic laxatives when initiating opioids – constipation is nearly universal with opioid use, and tolerance does not develop 2

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Special Population Considerations

Opioid-Induced Constipation

Prescribe concomitant laxatives prophylactically: osmotic (PEG or lactulose) plus stimulant (senna or bisacodyl) are preferred. 1, 2

• Bulk agents are contraindicated and may worsen symptoms 1, 2
• If response to laxatives is insufficient, consider peripherally acting mu-opioid receptor antagonists (methylnaltrexone, naloxegol, naldemedine) as rescue therapy 4

Renal Impairment

PEG is the safest option due to minimal systemic absorption. 1, 2

• Absolutely avoid magnesium-containing products 1, 2
• Lactulose is safe and may provide renoprotective effects 1
• Avoid bulk-forming laxatives, especially in patients with fluid restrictions 1

Pregnancy

Both PEG and psyllium are considered safe during pregnancy due to lack of systemic absorption, though PEG is preferred for efficacy 2

Elderly Patients

PEG 17g daily offers an excellent safety profile in elderly patients 2

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Non-Pharmacologic Adjuncts

While pharmacologic therapy is the cornerstone, these measures can support treatment:

• Proper toileting position: Use a footstool to assist gravity and pressure during defecation 1
• Scheduled defecation attempts: Twice daily, ideally 30 minutes after meals, straining no more than 5 minutes 1
• Regular exercise: Some evidence supports benefit, particularly for constipation symptoms 4

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Management of Fecal Impaction

Use glycerine suppositories or isotonic saline enemas as first-line therapy for fecal impaction. 1

• Avoid in patients with neutropenia, thrombocytopenia, or recent colorectal surgery 1, 2

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When to Escalate Beyond First and Second Line

If symptoms remain refractory after 3 months of optimized PEG plus stimulant laxative therapy:

• Reassess for mechanical obstruction, hypercalcemia, or medication causes 4
• Consider third-line agents: Intestinal secretagogues (lubiprostone, linaclotide) or prokinetic agents 4, 3
• Refer to gastroenterology for anorectal testing to evaluate for defecatory disorders, which may respond to biofeedback therapy 4, 5