What are the recommended pharmacologic options for treating functional or chronic constipation in adults, including management of opioid‑induced constipation and considerations for pregnant, lactating, and elderly patients?

Pharmacologic Management of Constipation in Adults

First-Line Treatment for Chronic Idiopathic Constipation

Polyethylene glycol (PEG) is the recommended first-line pharmacologic agent for chronic idiopathic constipation in adults, with the strongest evidence supporting its efficacy, tolerability, and cost-effectiveness. 1

• The 2023 AGA-ACG joint guidelines provide a strong recommendation for PEG based on moderate-quality evidence demonstrating durable response over 6 months 1, 2
• Common side effects include abdominal distension, loose stool, flatulence, and nausea, which are generally well-tolerated 2
• PEG should be trialed for at least 4-6 weeks before escalating therapy 2

Alternative Over-the-Counter Options

If PEG is not tolerated or preferred, consider these agents in order:

• Sodium picosulfate receives a strong recommendation for short-term use, but is contraindicated in patients with congestive heart failure, hypermagnesemia, severe renal impairment, and carries increased hyponatremia risk in elderly patients (≥65 years) 1, 2
• Bisacodyl receives a strong recommendation for short-term use (≤4 weeks) or rescue therapy and can be combined with other agents 1, 2
• Fiber supplements (polycarbophil, methylcellulose, psyllium) receive only a conditional recommendation and should be slowly increased over several weeks to minimize adverse effects 1, 3
• Senna receives a conditional recommendation with low-quality evidence; start with low doses and titrate 1, 2
• Lactulose receives a conditional recommendation 1
• Magnesium oxide receives a conditional recommendation but is contraindicated in patients with creatinine clearance <20 mL/min due to hypermagnesemia risk 1, 2

Critical Pitfall: Avoid Docusate

Docusate (stool softener) is not recommended for constipation management as it has not shown benefit in clinical trials. 4, 3

Second-Line Prescription Agents for Refractory Chronic Constipation

When OTC agents fail after 4-6 weeks, escalate to prescription therapies:

Secretagogues (Strong Recommendations)

• Linaclotide 145 mcg orally once daily receives a strong recommendation as the preferred prescription agent 1, 2
• Plecanatide receives a strong recommendation as an alternative secretagogue with similar mechanism to linaclotide 1, 2
• Lubiprostone receives only a conditional recommendation (weaker evidence than linaclotide/plecanatide) 1

Prokinetic Agent

• Prucalopride (serotonin type 4 agonist) receives a strong recommendation and works through a different mechanism than osmotic/stimulant laxatives, making it useful when secretagogues fail 1, 2

Opioid-Induced Constipation: Distinct Management Approach

Initial Assessment and Prevention

Before treating opioid-induced constipation (OIC), rule out bowel obstruction and fecal impaction with physical exam including digital rectal exam, and consider plain abdominal X-ray if mechanical obstruction is suspected. 1, 4

Treatment Algorithm for OIC

Step 1: Prophylactic laxatives at opioid initiation

• Start osmotic laxatives (PEG preferred) or stimulant laxatives (bisacodyl, senna) when initiating opioid therapy 1, 5, 6
• Goal: one non-forced bowel movement every 1-2 days 1

Step 2: Add or switch laxatives if constipation develops

• Add stimulant laxatives (bisacodyl, senna) or additional osmotic agents (lactulose, sorbitol, PEG) 1
• Magnesium-based products may be helpful but avoid in renal dysfunction 1
• Consider opioid rotation to fentanyl or methadone 1

Step 3: Peripherally acting μ-opioid receptor antagonists for refractory OIC

When laxatives fail, peripherally acting μ-opioid receptor antagonists are the evidence-based next step:

• Methylnaltrexone (subcutaneous 0.15 mg/kg or 12 mg for patients 62-114 kg): FDA-approved for OIC in advanced illness receiving palliative care 1, 4, 7
• Naloxegol: FDA-approved for OIC in chronic non-cancer pain 1
• Naldemedine: FDA-approved for OIC in chronic non-cancer pain 1

These agents should not be used in patients with known or suspected mechanical bowel obstruction 1, 7

Critical Pitfall: Bulk Laxatives Not Recommended for OIC

Psyllium and other bulk laxatives are not recommended for opioid-induced constipation. 4

Medication Interactions

Ondansetron (5-HT3 antagonist) significantly worsens constipation and should be avoided or used cautiously in patients with existing constipation; consider alternative antiemetics. 4

Special Populations

Elderly Patients

• All agents used for constipation must be individually evaluated in elderly patients due to altered absorption, distribution, metabolism, and excretion 5
• Sodium picosulfate carries increased hyponatremia risk (absolute risk increase 0.05%) in patients ≥65 years 2
• Avoid long-term magnesium-based laxatives due to potential toxicity 3

Renal Impairment

• Magnesium-based products are contraindicated when creatinine clearance <20 mL/min 2
• Methylnaltrexone requires dose adjustment in severe renal impairment 7
• Sodium phosphate enemas should be limited to maximum once daily or avoided in patients at risk for renal dysfunction 1

Hematologic Considerations

Rectal suppositories and enemas should be avoided in patients with neutropenia or thrombocytopenia. 1

Pregnancy and Lactation

• PEG and fiber supplements are generally considered safe options 1
• Methylnaltrexone labeling includes pregnancy and lactation considerations requiring individual risk-benefit assessment 7