What medications are recommended for treating constipation?

Medications for Constipation

Start with polyethylene glycol (PEG) 3350 at 17 grams daily dissolved in 4-8 ounces of water as first-line therapy for constipation, as it is the most effective, cost-efficient, and well-tolerated option with proven long-term safety. 1, 2

First-Line Treatment: Osmotic Laxatives

Polyethylene glycol (PEG) 3350 is the gold standard initial treatment:

• Dose 17 grams daily mixed in 4-8 ounces of water, juice, soda, coffee, or tea 1, 2, 3
• First bowel movement typically occurs within 2-4 days 3
• Titrate dose upward based on symptom response with no clear maximum dose 1, 2
• Monthly cost: $10-$45, making it highly cost-effective 1
• Proven durable response over 6-12 months of continuous use 1, 4
• Common side effects include bloating, abdominal discomfort, and cramping 1, 3

Alternative osmotic laxatives if PEG is not tolerated:

• Magnesium oxide 400-500 mg daily, but use with extreme caution in renal insufficiency and pregnancy 1, 2
• Lactulose 15 grams daily (only osmotic agent studied in pregnancy), though bloating and flatulence may limit tolerability 1, 2

Fiber supplementation:

• Recommend 14 grams per 1,000 kcal of dietary intake daily 1, 2
• Ensure adequate hydration as fiber intake increases 1
• Avoid medicinal fiber supplements like psyllium, which are ineffective and may worsen constipation 1

Second-Line Treatment: Stimulant Laxatives

Use stimulant laxatives for short-term rescue therapy or when osmotic laxatives provide inadequate response:

• Bisacodyl 5 mg daily (maximum 10 mg daily) 1, 2
• Senna 8.6-17.2 mg daily (maximum 4 tablets twice daily) 1, 2
• These agents are recommended for short-term use only, as long-term safety and efficacy are unknown 1
• Side effects include cramping and abdominal discomfort 1
• Prolonged or excessive use can cause diarrhea and electrolyte imbalance 1

Prescription Medications for Refractory Cases

Intestinal secretagogues when first-line and second-line treatments fail:

• Lubiprostone 24 mcg twice daily (monthly cost ~$374), which may provide additional benefit for abdominal pain 1, 2
• Linaclotide 72-145 mcg daily, titrate to maximum 290 mcg daily (monthly cost ~$523), also beneficial for abdominal pain 1, 2
• Plecanatide 3 mg daily with no titration needed (monthly cost ~$526) 1, 2
• Diarrhea may occur in a subset of patients with these agents, leading to discontinuation 1

Prokinetic agent for refractory constipation:

• Prucalopride 1-2 mg daily (maximum 2 mg daily, monthly cost ~$563), a serotonin type 4 receptor agonist that enhances colonic motility 1, 2
• May provide additional benefit for abdominal pain 1, 2
• Headaches and diarrhea may occur in some patients 1

Special Populations: Opioid-Induced Constipation

Prophylactic bowel regimen is mandatory for nearly all patients taking opioids:

• Start a stimulant laxative (sennosides alone, NOT with docusate) or PEG 17 grams twice daily at opioid initiation 1
• Docusate has not shown benefit and is not recommended 1
• Patients do not develop tolerance to opioid-induced constipation 1

For established opioid-induced constipation:

• Rule out bowel obstruction and hypercalcemia 1
• Add stimulant laxatives (bisacodyl 10-15 mg daily to three times daily) with goal of one non-forced bowel movement every 1-2 days 1
• Consider adding magnesium-based products, osmotic laxatives (sorbitol, lactulose, PEG), or bisacodyl suppositories 1
• Opioid rotation to fentanyl or methadone may reduce constipation 1

Peripherally acting mu-opioid receptor antagonists for rescue when laxatives fail:

• Methylnaltrexone 0.15 mg/kg subcutaneously every other day (FDA-approved for opioid-induced constipation in advanced illness receiving palliative care) 1
• Naloxegol or naldemedine (FDA-approved for opioid-induced constipation in chronic noncancer pain) 1
• Do NOT use in known or suspected mechanical bowel obstruction 1

Special Populations: Palliative Care

For patients with limited life expectancy (weeks to days):

• Increase dose of stimulant laxative (senna 2-3 tablets 2-3 times daily) with goal of one non-forced bowel movement every 1-2 days 1
• Glycerine suppository or mineral oil retention enema for impaction 1
• Manual disimpaction following pre-medication with analgesic and anxiolytic if needed 1
• Avoid rectal suppositories or enemas in patients with neutropenia or thrombocytopenia 1

Critical Pitfalls to Avoid

Do not use docusate as prophylaxis or treatment:

• Multiple randomized controlled trials show no benefit when added to sennosides compared to sennosides alone 1

Rule out bowel obstruction before escalating laxative therapy:

• Perform physical exam and consider abdominal x-ray if constipation persists despite treatment 1
• Secretagogues and opioid antagonists should NOT be used in mechanical bowel obstruction 1

Limit sodium phosphate products:

• Use sparingly with awareness of electrolyte abnormalities 1
• Limit to maximum once daily in patients at risk for renal dysfunction 1

Monitor for electrolyte imbalance with prolonged laxative use:

• Prolonged, frequent, or excessive use may result in electrolyte imbalance and laxative dependence 3