What are the recommended laxatives for managing constipation in patients taking opioids?

Laxatives for Opioid-Induced Constipation

All patients starting opioid therapy should be prophylactically prescribed osmotic laxatives (polyethylene glycol, lactulose) or stimulant laxatives (senna, bisacodyl) unless contraindicated by pre-existing diarrhea. 1

Prophylactic First-Line Therapy

Start laxatives immediately when initiating opioids—do not wait for constipation to develop. 1, 2

• Osmotic laxatives (polyethylene glycol, lactulose, magnesium salts) are preferred first-line options 1
• Stimulant laxatives (senna, bisacodyl, sodium picosulfate) are equally preferred as first-line options 1
• The combination of senna with docusate (stool softener) is specifically recommended by NCCN, starting with 2 tablets every morning, maximum 8-12 tablets per day 1, 2
• Escalate laxative doses when increasing opioid doses—this is a critical step often missed 2

Laxatives to Avoid

• Bulk-forming laxatives (psyllium, Metamucil) are NOT recommended for opioid-induced constipation and are unlikely to be effective 1, 2
• Avoid liquid paraffin in bed-bound patients or those with swallowing disorders due to aspiration pneumonia risk 1

Goal of Therapy

• Achieve one non-forced bowel movement every 1-2 days 1, 2

When Constipation Develops Despite Prophylaxis

Before escalating therapy, rule out bowel obstruction and check for fecal impaction via digital rectal examination. 1, 2

Escalation Algorithm:

1. Increase current laxative dose or add a second agent from a different class 1, 2

   • Add magnesium hydroxide 30-60 mL daily 1
   • Add bisacodyl 2-3 tablets daily 1
   • Add lactulose 30-60 mL daily 1
   • Add polyethylene glycol (17g/day, especially safe in elderly) 1

2. If rectal loading or impaction is present on digital rectal exam:

   • Suppositories (bisacodyl) or enemas are first-line for rectal impaction 1
   • Fleet, saline, or tap water enema 1

3. Consider adding a prokinetic agent (metoclopramide 10-20 mg PO 3-4 times daily) 1

Critical Contraindications and Cautions

• Magnesium salts can cause hypermagnesemia—use cautiously in renal impairment 1
• Enemas are contraindicated in neutropenia, thrombocytopenia, paralytic ileus, intestinal obstruction, recent colorectal/gynecological surgery, recent anal/rectal trauma, severe colitis, toxic megacolon, undiagnosed abdominal pain, or recent pelvic radiotherapy 1

Laxative-Refractory Opioid-Induced Constipation

For patients with inadequate response to traditional laxatives after appropriate escalation, peripherally acting μ-opioid receptor antagonists (PAMORAs) should be considered. 1, 2

PAMORA Options:

• Naldemedine is strongly recommended (high-quality evidence) 2
• Methylnaltrexone is conditionally recommended (low-quality evidence) 2
  • For chronic non-cancer pain: 12 mg subcutaneously once daily or 450 mg orally once daily 3
  • For advanced illness/cancer pain: 8-12 mg subcutaneously every other day (weight-based dosing) 3
  • Dose reduction required in moderate-severe renal impairment (CrCl <60 mL/min) and severe hepatic impairment 3
• Naloxone combined with opioid formulations reduce risk of opioid-induced constipation 1

Supportive Non-Pharmacologic Measures

• Maintain adequate fluid intake 1, 2
• Encourage physical activity if feasible 1, 2
• Ensure privacy, comfort, and proper positioning (footstool to assist gravity) 1
• Optimize toileting: attempt defecation twice daily, 30 minutes after meals, strain no more than 5 minutes 1
• Abdominal massage may help, particularly in patients with neurogenic problems 1

Common Pitfalls to Avoid

• Failing to start prophylactic laxatives when initiating opioids 2
• Not escalating laxative doses when increasing opioid doses 2
• Using bulk-forming laxatives as first-line therapy 1, 2
• Not ruling out bowel obstruction before aggressive laxative therapy 1, 2
• Discontinuing all maintenance laxatives when starting PAMORAs—laxatives can be used as needed if suboptimal response after 3 days 3