What is the first-line pharmacological treatment for constipation?

First-Line Pharmacological Treatment for Constipation

Polyethylene glycol (PEG) 17 grams once daily is the recommended first-line pharmacological treatment for chronic constipation, based on strong evidence from the 2023 AGA-ACG joint guidelines. 1

Why PEG is First-Line

• The AGA-ACG guidelines make a strong recommendation for PEG over management without PEG, supported by moderate certainty evidence 1
• PEG increases complete spontaneous bowel movements (CSBMs) by 2.90 per week and spontaneous bowel movements (SBMs) by 2.30 per week compared to placebo 1
• Response to PEG is durable over 6 months, making it suitable for chronic management 1, 2
• PEG has virtually no net gain or loss of sodium and potassium, providing a superior safety profile compared to magnesium-based osmotic laxatives 1, 2

Practical Dosing Algorithm

Start with PEG 17 grams (one heaping tablespoon) mixed in 8 ounces of water once daily 1, 2

• Take on an empty stomach, at least 30 minutes before a meal, at approximately the same time each day 1
• If inadequate response after 2-3 days, add a stimulant laxative (bisacodyl 5-10 mg daily or senna 8.6-17.2 mg daily) rather than increasing PEG dose initially 1, 2
• PEG can be titrated upward based on symptom response, with no clear maximum dose 1
• For patients unable to swallow capsules, PEG powder formulations are available and easily administered 1

Alternative First-Line Options (When PEG is Not Suitable)

For mild constipation or patients preferring to start conservatively, fiber supplementation (14 g per 1,000 kcal intake) can be tried before PEG 1

• Ensure adequate fluid intake (8-10 ounces with each fiber dose) to prevent stool hardening 1
• Common side effects include flatulence and bloating, which may limit tolerability 1
• Fiber is most appropriate for those with dietary fiber deficiency and mild-to-moderate symptoms 1

Lactulose 15 grams daily is a conditional recommendation as an alternative osmotic laxative 1

• Lactulose is the only osmotic agent studied in pregnancy, making it preferred in pregnant patients 1
• Bloating and flatulence may be more limiting than with PEG, especially at higher doses 1
• PEG is superior to lactulose for stool frequency, stool form, and relief of abdominal pain based on meta-analysis 3

Second-Line Prescription Options

If PEG plus stimulant laxatives fail after adequate trial (4+ weeks), escalate to prescription secretagogues or prokinetics 1

The 2023 AGA-ACG guidelines provide strong recommendations for:

• Linaclotide 145 mcg daily (or 72 mcg daily based on tolerability) 1, 4
• Plecanatide 3 mg daily 1
• Prucalopride 1-2 mg daily 1
• Sodium picosulfate (stimulant laxative with strong evidence) 1

These agents cost $374-$563 per month compared to $10-$45 for PEG 1

Critical Pitfalls to Avoid

Never use magnesium-based osmotic laxatives (magnesium oxide, magnesium citrate) in patients with renal insufficiency due to risk of hypermagnesemia 1, 2

Avoid bulk laxatives (psyllium, methylcellulose) in opioid-induced constipation as they are ineffective and may worsen symptoms 1, 2

Do not recommend docusate (stool softener) - it works only as a surfactant and has not shown clinical benefit in evidence-based studies 2

Stimulant laxatives (bisacodyl, senna) should not be used as monotherapy long-term - they are recommended for short-term use, rescue therapy, or in combination with osmotic laxatives 1

Special Populations

For IBS with constipation (IBS-C): PEG and stimulant laxatives are reasonable first-line options, though evidence is limited compared to chronic idiopathic constipation 1

For elderly patients: PEG 17 grams daily offers efficacy with good safety profile, with no dose adjustment needed 5, 6

For opioid-induced constipation: Prophylactic PEG or stimulant laxatives are mandatory from the start of opioid therapy 2

Common Side Effects and Management

PEG side effects include 1:

• Abdominal distension and bloating
• Loose stools or diarrhea (dose-dependent)
• Flatulence
• Nausea

These effects are generally mild to moderate and can be managed by dose reduction or temporary discontinuation 1, 6