PAMORA Comparison Tool
Compare the three FDA-approved PAMORAs for opioid-induced constipation (OIC). This tool helps you understand key differences based on administration method, effectiveness, cost, and patient considerations.
Important note: This tool is for informational purposes only. Always consult your healthcare provider for medical advice and treatment decisions.
Comparison Table
| Methylnaltrexone (RELISTOR) | Naloxegol (MOVANTIK) | Naldemedine (SYMPROIC) | |
|---|---|---|---|
| Route of Administration | Subcutaneous injection or oral tablet | Oral tablet | Oral tablet |
| Onset of Action | 4 hours | 24-48 hours | 24-48 hours |
| FDA Approval | Cancer & noncancer chronic pain | Noncancer chronic pain | Cancer & noncancer chronic pain |
| Liver Considerations | Does not require dose adjustment | Requires dose adjustment for liver problems | Generally safe for liver issues |
| Kidney Considerations | Requires dose adjustment for severe kidney impairment | Not recommended for severe kidney impairment | Minimal adjustment needed for mild-to-moderate kidney issues |
| Cost | $5,000-$6,000/year | $5,000-$6,000/year | $5,000-$6,000/year |
| Effectiveness | 52% response rate | 44% response rate | 48% response rate |
| Side Effects | Abdominal cramping (common) | Abdominal pain, nausea | Diarrhea, cramping |
Who Is Each PAMORA Right For?
For Cancer Patients: Methylnaltrexone is generally preferred due to its dual approval for cancer and noncancer pain, and rapid action.
For Noncancer Chronic Pain: Naloxegol or naldemedine are often first-line choices as daily oral medications.
For Patients on Multiple Medications: Methylnaltrexone is often preferred due to fewer drug interactions (doesn't affect CYP3A4 enzymes).
For Severe Kidney Impairment: Naldemedine is generally the safest option. Methylnaltrexone requires dose reduction, while naloxegol is not recommended.
For Liver Problems: Naldemedine is usually safer than naloxegol, which requires dose adjustment. Methylnaltrexone has the fewest liver-related issues.
Cost Considerations
A year's supply of PAMORAs typically costs $5,000-$6,000 without insurance. With insurance, copays can range from $400-$500 per month.
Manufacturer Support
Most manufacturers offer patient assistance programs, coupons, and copay cards. These can significantly reduce out-of-pocket costs.
Some programs provide free trials or $0 copays for the first 3 months.
Alternative Option
Lubiprostone (Amitiza) costs around $2,000/year but is less effective (30-35% response rate) compared to PAMORAs (45-50%).
Not FDA-approved for OIC specifically, though sometimes used off-label.
Future Cost Changes
Biosimilars (like methylnaltrexone biosimilar) may enter the market by 2027, potentially reducing costs by 30-50%.
Expect to pay more for brand-name PAMORAs through 2026.
Quick Decision Guide
Are you a cancer patient?
Do you have severe kidney impairment?
Are you on multiple medications?
When you're taking opioids for chronic pain or cancer-related discomfort, constipation isn't just an inconvenience-it can make your treatment unbearable. Up to 80% of people on long-term opioids develop opioid-induced constipation (OIC), and traditional laxatives often fail to help. That’s where peripherally acting mu-opioid receptor antagonists (PAMORAs) come in. These drugs don’t touch your pain relief but fix the gut problem opioids cause.
Why Opioids Cause Constipation
Opioids bind to mu-receptors in your gut, slowing down everything. Food moves slower, fluids get absorbed too much, and your bowels stop working like they should. It’s not just about being ‘regular’-it’s about safety. Severe constipation can lead to bowel obstruction, nausea, vomiting, and even hospitalization. Many patients stop taking their pain meds because of this, which means their pain comes back worse.What Are PAMORAs?
PAMORAs are designed to block opioid effects only in the digestive tract. They don’t cross the blood-brain barrier, so your pain control stays intact. This is the key difference from older treatments. You’re not fighting your pain medication-you’re fixing its side effect.The Three Main PAMORAs
There are three FDA-approved PAMORAs on the market, each with different strengths and uses:- Methylnaltrexone (RELISTOR): Available as a subcutaneous injection or oral tablet. Approved for both cancer and noncancer chronic pain patients. Works fast-many people have a bowel movement within 4 hours. It’s not broken down by liver enzymes, so it plays nice with other meds.
- Naloxegol (MOVANTIK): An oral tablet taken once daily. Designed specifically for OIC in adults with noncancer pain. Requires dose adjustment if you have liver problems. Half-life is longer than methylnaltrexone, so it lasts longer in your system.
- Naldemedine (SYMPROIC): Also taken once daily by mouth. Works well for both cancer and noncancer patients. Has a polyethylene glycol chain that keeps it out of the brain. Shown to increase spontaneous bowel movements by nearly 50% in clinical trials.
How Effective Are They?
Clinical data shows these drugs work better than laxatives:- Methylnaltrexone: 52% of patients had a bowel movement within 4 hours vs. 30% on placebo.
- Naloxegol: 44% achieved regular bowel movements at 12 weeks vs. 27% on placebo.
- Naldemedine: 48% response rate vs. 35% on placebo.
Who Should Use Them?
PAMORAs are meant for adults with chronic opioid use who haven’t responded to laxatives. They’re especially helpful for:- Cancer patients on palliative care needing consistent comfort
- People with osteoarthritis or back pain on daily opioids
- Those who’ve tried fiber, stool softeners, osmotic laxatives, and stimulants with no success
Side Effects and Risks
Most side effects are mild: abdominal pain, diarrhea, nausea, and gas. But about 30% of users report cramping, especially early on. Some patients describe it as intense but short-lived-usually fades after a few doses. One rare but serious concern is the risk of opioid withdrawal in the gut. This isn’t full-blown withdrawal like with addiction-it’s just your bowels reacting. You might feel sudden urgency or discomfort, but it doesn’t affect your pain control. Alvimopan (ENTREGOR), another PAMORA, is only used in hospitals after bowel surgery because of heart risks. It’s not used for chronic OIC.Cost and Accessibility
This is the biggest hurdle. A year’s supply of PAMORAs can cost $5,000-$6,000 without insurance. Even with coverage, copays can hit $400-$500 per month. Patient reviews on platforms like GoodRx and Reddit reflect this frustration. One 67-year-old with osteoarthritis said: “Naloxegol worked for two weeks, then stopped. I paid $450 a month for nothing.” But cancer patients often report better outcomes. On r/palliativecare, 65% said methylnaltrexone “saved their quality of life.” Many use manufacturer coupons or patient assistance programs to bring costs down.
Dosing and Timing
Getting the timing right matters. PAMORAs work best when taken about 1 hour before your regular opioid dose-right when the opioid peaks in your system. This lets the PAMORA block the gut receptors just as the opioid starts slowing things down. Methylnaltrexone injections are usually given by a nurse at first, then patients can self-administer. Oral forms can be started right away by your doctor. All three require dose adjustments if you have kidney problems:- Methylnaltrexone: Cut dose in half if creatinine clearance is under 30 mL/min
- Naloxegol: Not recommended if kidney function is severely impaired
- Naldemedine: No major adjustment needed for mild-to-moderate kidney issues
How Doctors Decide Which One to Prescribe
There’s no one-size-fits-all. Here’s how most pain specialists choose:- For cancer patients: Methylnaltrexone is preferred because it’s approved for both cancer and noncancer use, and it works fast. Many hospice teams keep it on hand.
- For chronic noncancer pain: Naloxegol or naldemedine are first-line because they’re daily pills. Easier to manage long-term.
- For patients on multiple meds: Methylnaltrexone wins-it doesn’t interact with CYP3A4 enzymes, so it won’t interfere with statins, blood thinners, or antidepressants.
What’s Next?
New developments are on the horizon. In early 2023, a new 300 mg tablet of methylnaltrexone was approved for patients who don’t respond to the standard dose. Researchers are also testing a combo drug that combines a PAMORA with a serotonin agonist-early results show a 68% success rate. Biosimilars are coming too. The first methylnaltrexone biosimilar is in phase 3 trials in China and could enter the U.S. market by 2027, potentially cutting costs by 30-50%. Still, the American Gastroenterological Association warns: without price drops, only 35-40% of people who need PAMORAs will ever get them. Many end up stuck with ineffective laxatives or worse-reducing their opioid dose, which brings back the pain.Final Thoughts
Opioid constipation isn’t something you just have to live with. PAMORAs offer a targeted, science-backed solution that doesn’t sacrifice pain control. They’re not perfect-they’re expensive and can cause cramping-but for many, they’re the only thing that restores dignity and comfort to daily life. If you’ve been struggling with constipation while on opioids, talk to your doctor about PAMORAs. Ask which one fits your situation, whether your insurance covers it, and if there’s a patient support program you can join. This isn’t just about bowel movements-it’s about being able to live without constant discomfort.Are PAMORAs safe for long-term use?
Yes, for most people. Methylnaltrexone, naloxegol, and naldemedine have been studied for up to 12 months with no new safety signals beyond known side effects like abdominal cramping and diarrhea. Long-term use doesn’t reduce effectiveness, and there’s no evidence of tolerance development. However, they’re not approved for use beyond 12 months in some countries, so ongoing monitoring is recommended.
Can I take PAMORAs with other laxatives?
Yes, but it’s usually not necessary. PAMORAs are more effective than standard laxatives for opioid-induced constipation. If you’re still having trouble after a week on a PAMORA, your doctor might add a mild osmotic laxative like polyethylene glycol-but avoid stimulant laxatives like senna, which can worsen cramping.
Do PAMORAs cause opioid withdrawal?
No, not in the brain. PAMORAs are designed to stay out of the central nervous system, so they don’t trigger withdrawal symptoms like nausea, sweating, or anxiety. Some people report gut-specific discomfort-like sudden urgency or cramping-which is the drug working as intended, not true withdrawal. If you feel systemic withdrawal symptoms, talk to your doctor immediately.
Why isn’t my doctor prescribing a PAMORA?
Many doctors still think laxatives are enough. Others worry about cost or don’t know the latest guidelines. You can ask: “Based on my opioid dose and how often I’m constipated, would a PAMORA be appropriate?” Bring up the 2023 American Pain Society survey showing 78% of pain specialists prefer PAMORAs over laxatives for OIC. Most will reconsider if you’re persistent and informed.
Is there a cheaper alternative to PAMORAs?
Lubiprostone (Amitiza) is a chloride channel activator approved for OIC and costs less-around $2,000 a year. But it’s less effective: only 30-35% of patients respond, compared to 45-50% with PAMORAs. Fiber and fluids help a little, but won’t fix opioid-induced motility slowdown. If cost is an issue, ask about manufacturer coupons or patient assistance programs-many offer free trials or $0 copays for the first 3 months.
Can I switch between PAMORAs if one doesn’t work?
Yes. If one PAMORA doesn’t work after 2-4 weeks, switching to another is common practice. Studies show about 20-30% of patients who don’t respond to naloxegol will respond to naldemedine or methylnaltrexone. It’s trial and error-but you’re not starting from scratch. Your body has already adapted to the mechanism, so switching often works.
How soon will I feel results?
With methylnaltrexone injection, you can have a bowel movement within 30 minutes to 4 hours. Oral forms take longer-naloxegol and naldemedine usually work within 24-48 hours. Most people notice improvement within 3-5 days. If you haven’t had a bowel movement by day 5, contact your doctor. You may need a dose adjustment or a different PAMORA.
Do PAMORAs work for post-op constipation?
Only alvimopan is approved for this, and only in hospitals after bowel surgery. It’s not used for general post-op constipation. For most patients recovering from other surgeries, standard laxatives or early mobility are still first-line. PAMORAs like methylnaltrexone aren’t typically used unless the patient is already on chronic opioids before surgery.
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