What are the recommended pharmacologic treatments for uncomplicated constipation in adults, including first‑line agents, rescue options, and special considerations such as opioid‑induced constipation?

Pharmacologic Management of Constipation in Adults

First-Line Treatment for Chronic Idiopathic Constipation

For uncomplicated chronic constipation, polyethylene glycol (PEG) is the recommended first-line agent with the strongest evidence base, dosed at 17 grams in 8 oz of water twice daily. 1

• PEG has a strong recommendation with moderate certainty of evidence and has demonstrated durable response over 6 months 1
• Side effects include abdominal distension, loose stool, flatulence, and nausea 1
• For mild constipation, psyllium fiber supplementation may be tried first or in combination with PEG, though the evidence is weaker (conditional recommendation, low certainty) 1
• Adequate hydration must be encouraged with fiber use to prevent worsening constipation 1

Alternative First-Line Options

• Stimulant laxatives (senna, bisacodyl, sodium picosulfate) are equally acceptable first-line options 1
• Other osmotic laxatives including lactulose, sorbitol, and magnesium-based products are effective 1
• Magnesium salts should be used cautiously in renal impairment due to risk of hypermagnesemia 1

What NOT to Use

• Docusate (stool softeners) have not shown benefit and are not recommended 1
• Supplemental fiber like psyllium is ineffective for opioid-induced constipation and may worsen symptoms 1

Opioid-Induced Constipation: Prophylaxis

All patients starting opioid therapy should receive prophylactic laxatives unless they have pre-existing diarrhea. 1, 2

Recommended Prophylactic Regimen

• PEG 17 grams in 8 oz water twice daily PLUS senna 2 tablets twice daily 1, 2
• This combination targets both osmotic and stimulant mechanisms 2
• Patients do not develop tolerance to opioid-induced constipation, so prophylaxis must continue throughout opioid therapy 2
• Increase laxative doses when opioid doses are increased 2

Goal of Therapy

• Target one non-forced bowel movement every 1-2 days 1, 2
• Titrate laxatives based on response, not on a fixed schedule 2

Rescue Therapy for Persistent Constipation

When First-Line Laxatives Fail

If constipation persists despite adequate laxative therapy, reassess to rule out bowel obstruction or impaction before escalating treatment. 1

Step 1: Intensify Conventional Laxatives

• Add or increase stimulant laxatives: bisacodyl tablets/suppositories, magnesium hydroxide 30-60 mL daily, or increase osmotic laxatives 1, 2
• Consider lactulose 30-60 mL daily 2

Step 2: Rectal Interventions for Impaction

• Suppositories and enemas are preferred first-line therapy when digital rectal exam or imaging identifies a full rectum or fecal impaction 1, 2
• Bisacodyl suppository 10 mg stimulates local peristalsis 2
• If impaction is present, perform digital fragmentation and extraction 1, 2
• Follow with Fleet enema, saline enema, or tap water enema (500-700 mL) 1, 2

Critical contraindications for enemas: neutropenia, thrombocytopenia, recent colorectal/gynecological surgery, recent anal/rectal trauma, severe colitis, paralytic ileus, intestinal obstruction, toxic megacolon, or recent pelvic radiotherapy 1

Step 3: Peripherally Acting μ-Opioid Receptor Antagonists (PAMORAs)

When laxative therapy has been insufficient and constipation is clearly opioid-related, PAMORAs should be used as rescue therapy. 1

Available agents:

• Methylnaltrexone (FDA-approved for opioid-induced constipation in adults with advanced illness receiving palliative care): 0.15 mg/kg subcutaneously 1, 2, 3
• Naloxegol (FDA-approved for opioid-induced constipation in adults with chronic non-cancer pain) 1
• Naldemedine (FDA-approved for opioid-induced constipation in adults with chronic non-cancer pain) 1

These agents will not benefit and should not be used in patients with known or suspected mechanical bowel obstruction. 1

Step 4: Other Second-Line Agents

• Lubiprostone (FDA-approved for opioid-induced constipation in adults with non-cancer pain) 1
• Linaclotide (FDA-approved for idiopathic constipation, not specifically for opioid-induced) 1

Special Considerations

Elderly Patients with Cancer

• PEG 17 g/day offers an efficacious and tolerable solution with a good safety profile 1
• Ensure access to toilets, especially with decreased mobility 1
• Avoid liquid paraffin in bed-bound patients and those with swallowing disorders due to aspiration risk 1
• Monitor closely if on diuretics or cardiac glycosides due to risk of dehydration and electrolyte imbalances 1

Renal Impairment

• Sodium phosphate-containing laxatives or enemas should be limited to maximum once daily or alternative agents used 1
• Dosage adjustments for methylnaltrexone may be needed 3

Non-Pharmacologic Adjuncts

While insufficient alone for opioid-induced constipation, these measures support pharmacologic therapy:

• Increase fluid intake to at least 1.5 liters daily 1, 2
• Increase dietary fiber through fruits, vegetables, and whole grains 1, 2
• Mobilize as soon as safely possible 1, 2
• Ensure privacy and proper positioning for defecation 1, 2
• Abdominal massage may help, particularly in patients with neurogenic problems 1

Pain Management Optimization

• Consider multimodal analgesia to reduce opioid requirements 2
• Opioid rotation to fentanyl or methadone may reduce constipation 1
• Neuraxial analgesics or neuroablative techniques can reduce systemic opioid dose 1

Common Pitfalls to Avoid

• Do not use docusate alone - it lacks efficacy 1
• Do not add fiber supplements for opioid-induced constipation - they are ineffective and may worsen symptoms 1
• Do not use enemas in neutropenic or thrombocytopenic patients 1
• Always rule out obstruction before escalating therapy 1
• Do not forget prophylaxis - waiting for constipation to develop makes it harder to treat 1, 2