Opioid-Induced Constipation: How to Prevent and Treat It Effectively

When you start taking opioids for chronic pain, you’re told about drowsiness, nausea, and the risk of dependence. But one of the most common and frustrating side effects? Constipation. In fact, opioid-induced constipation affects 40% to 60% of people taking these medications-even if they’ve never had bowel problems before. And unlike other side effects that fade over time, OIC doesn’t go away. It sticks with you for as long as you’re on opioids.

Why Opioids Cause Constipation

Opioids don’t just slow down your brain-they slow down your gut. They bind to μ-opioid receptors in the walls of your intestines, which are meant to control movement. When these receptors are activated, your gut muscles relax. Food and waste move slower. Water gets sucked out of your stool, making it hard and dry. Your anal sphincter tightens, making it harder to push out even when you feel the urge.

This isn’t just a minor inconvenience. Left untreated, OIC can lead to bloating, nausea, vomiting, loss of appetite, and even fecal impaction-a serious blockage that may require hospitalization. Patients often describe it as straining for minutes with no results, or feeling like they haven’t fully emptied their bowels. And because it’s so common, many assume it’s just "normal" with pain meds. It’s not. And it doesn’t have to be.

Prevention Starts on Day One

The biggest mistake doctors and patients make? Waiting for constipation to happen before doing something about it. Experts agree: if you’re starting opioids, you should start a laxative the same day. Proactive treatment cuts severe OIC cases by 60-70%.

Start with two simple, over-the-counter options:

• Polyethylene glycol (PEG)-an osmotic laxative that pulls water into the colon to soften stool. It’s gentle, doesn’t cause cramping, and works well for long-term use.
• Senna or bisacodyl-stimulant laxatives that trigger muscle contractions in the bowel. Use these for short-term relief or if PEG alone isn’t enough.

Don’t rely on stool softeners like docusate. Studies show they’re largely ineffective for OIC. They work for occasional constipation from dehydration or diet, but not for opioid-driven gut paralysis.

Alongside medication, make small lifestyle changes:

• Drink at least 2 liters of water daily
• Move regularly-even a 10-minute walk after meals helps
• Get fiber from fruits, vegetables, and whole grains, but don’t overdo it. Too much fiber without enough water can make things worse

When Over-the-Counter Laxatives Aren’t Enough

About two out of three people on opioids find that standard laxatives just don’t cut it. That’s because OIC works differently than regular constipation. You can’t just add bulk or stimulate the gut-you need to block the opioid effect right where it’s happening: in the intestines.

That’s where peripherally acting μ-opioid receptor antagonists (PAMORAs) come in. These are prescription drugs designed to undo opioid effects in the gut without touching pain relief in the brain.

Here are the four main PAMORAs used today:

Comparison of PAMORAs for Opioid-Induced Constipation

Medication	Form	Dosing	Onset	Key Considerations
Methylnaltrexone (Relistor®)	Injection or oral tablet	Once daily (tablet) or every other day (injection)	30 minutes (injection), 1-4 hours (tablet)	First approved PAMORA; works fast; not for people with bowel obstruction
Naldemedine (Symproic®)	Oral tablet	Once daily	12-24 hours	Also reduces opioid-induced nausea; approved for cancer patients
Naloxegol (Movantik®)	Oral tablet	Once daily	25 minutes to 6 hours	May interact with grapefruit juice and certain antibiotics
Lubiprostone (Amitiza®)	Oral capsule	Twice daily	24-48 hours	Only FDA-approved for women in initial trials, but works for men too; causes nausea in 1 in 3 users

These medications aren’t magic bullets. Some people get abdominal pain, cramping, or diarrhea. But for many, they’re life-changing. One patient on Reddit said, "Relistor injections work within 30 minutes when nothing else does." Another on PatientsLikeMe wrote, "Naldemedine has allowed me to stay on my pain medication without constant bathroom struggles."

Who Shouldn’t Use PAMORAs

Not everyone can take these drugs. They’re contraindicated if you have:

• A known or suspected bowel obstruction
• Recent abdominal surgery
• Active inflammatory bowel disease (like Crohn’s or ulcerative colitis)

There’s a small but serious risk of gastrointestinal perforation-the wall of the intestine tears. While rare, it’s life-threatening. That’s why the FDA requires special patient education materials with every prescription. If you suddenly get sharp abdominal pain, fever, or vomiting after starting a PAMORA, seek help immediately.

Cost and Access Are Major Barriers

PAMORAs can cost between $500 and $900 a month without insurance. Even with coverage, many insurers require prior authorization or step therapy-meaning you have to try and fail on cheaper laxatives first. A 2024 survey found that 41% of Medicare Part D plans and 28% of private plans impose these barriers.

And it’s not just about money. A study of 1,500 patients found that 57% stopped taking PAMORAs within six months-not because they didn’t work, but because of cost, side effects, or difficulty getting refills.

What’s New in 2025

The field is evolving. In 2023, the FDA approved a once-weekly injection of methylnaltrexone. That’s a big deal for patients who used to need daily shots. It reduces burden, improves adherence, and lowers the risk of missed doses.

The American Society of Clinical Oncology (ASCO) now recommends naldemedine as a first-line option for cancer patients starting opioids-not just to treat constipation, but to prevent it, and even reduce nausea at the same time.

Looking ahead, researchers are testing combination pills that pair low-dose PAMORAs with osmotic laxatives. There’s also early work on genetic testing to predict who will respond best to which drug. By 2026, personalized OIC treatment could become standard.

How to Talk to Your Doctor

If you’re on opioids and constipated:

1. Don’t wait. Ask for a bowel regimen right away.
2. Ask if polyethylene glycol and senna are right for you.
3. If those don’t help after 2-4 weeks, ask about PAMORAs.
4. Ask your pharmacist to review your meds-they catch interactions and dosing errors most doctors miss.
5. Track your bowel movements. Use the Bowel Function Index (BFI). A score above 30 means you need stronger treatment.

Pharmacists who actively follow up with opioid patients increase appropriate laxative use by 43%. Don’t assume your doctor knows. Bring this up. Keep a simple log: date, time, stool consistency (use the Bristol Stool Scale), and whether you felt fully empty.

The Bigger Picture

Opioid prescriptions have dropped since 2012, but over 73 million Americans still rely on them for chronic pain. That means millions are living with untreated OIC. The cost of ignoring it? $2.3 billion a year in avoidable ER visits, hospitalizations, and lost productivity.

The tools to fix this exist. We know how to prevent it. We have effective treatments. What’s missing is consistent action-from doctors, pharmacists, insurers, and patients.

You don’t have to accept constipation as part of your pain management. With the right plan, you can stay on your pain medication-and keep your bowels working.