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.
Sam Reicks
November 19, 2025 at 16:13So these PAMORAs are just another way for Big Pharma to charge us $5k a year for a drug that probably just makes your guts mad so you keep buying it
They say it dont affect the brain but i bet they lied like they did with oxycontin
My cousin took one and started hallucinating and screaming about the government putting wires in his colon
And now hes on disability and they say its the opioid but i know better
They just want us hooked on pills and then charge us more to fix the mess they made
Why dont they just let people quit opioids instead of selling us a new drug to fix the old one
Its all about the money not the patients
And dont get me started on the FDA theyre bought and paid for
Im not taking it
Chuck Coffer
November 20, 2025 at 16:11Wow. A drug that actually works for OIC? How quaint.
I suppose next they'll invent a pill that makes gravity optional.
At least the price tag is honest - you're paying for the privilege of not being constipated while your pain meds do their job.
Meanwhile, my uncle took laxatives for 12 years and still managed to live to 93.
Maybe the real issue is that people are too lazy to eat fiber.
Marjorie Antoniou
November 21, 2025 at 05:27I’ve been on naldemedine for 8 months now after years of suffering with severe OIC from my spinal fusion meds.
Before this, I was in tears every morning because I couldn’t go for days.
Now I have regular bowel movements and can actually leave the house without panic.
Yes, the cramping sucks at first - but it fades.
Yes, it’s expensive - but my patient assistance program cut it to $10 a month.
This isn’t a luxury. It’s dignity.
If you’re on opioids and still suffering, please talk to your doctor. You don’t have to live like this.
Andrew Baggley
November 22, 2025 at 23:00Listen - if you’re on opioids and constipated, you’re not broken.
You’re just dealing with a side effect that’s been ignored for decades.
PAMORAs aren’t magic, but they’re the closest thing we’ve got to a real fix.
And yeah, they cost a fortune - but so do ER visits from bowel obstructions.
Stop thinking of this as a ‘pill’ and start thinking of it as a ‘quality of life upgrade’.
My mom switched from methylnaltrexone injections to naldemedine and now she’s gardening again.
That’s worth more than any price tag.
Frank Dahlmeyer
November 23, 2025 at 05:18Let me tell you something - I’ve been in palliative care for five years now with metastatic prostate cancer, and I’ve tried everything: prunes, Miralax, enemas, senna, even acupuncture.
Nothing worked.
Then my nurse handed me a syringe of methylnaltrexone and said, ‘This is your life back.’
Within two hours, I had my first real bowel movement in 17 days.
I cried.
Not because it hurt - because I could finally sit down without fear.
Yes, it’s expensive.
Yes, it’s a shot.
But if you’re still using laxatives and suffering, you’re not being tough - you’re being stubborn.
There’s a better way. Don’t let cost or fear rob you of comfort.
Ask for it. Fight for it. You deserve it.
Codie Wagers
November 24, 2025 at 08:05The fundamental irony of PAMORAs is that they are a perfect metaphor for modern medicine: expensive, technically precise, and utterly disconnected from the root cause.
We are not treating constipation - we are treating the symptom of a society addicted to pharmaceutical solutions.
Why not address the opioid dependency itself?
Why not reduce doses?
Why not invest in physical therapy, acupuncture, or cognitive behavioral therapy for chronic pain?
Instead, we create a new drug to undo the damage of the old one - and call it progress.
It’s not science.
It’s capitalism with a stethoscope.
Paige Lund
November 26, 2025 at 00:22So… you pay $500 a month to not poop like a brick?
Sign me up.
Christopher K
November 26, 2025 at 19:30These drugs are made in China and sold by Jews who own the FDA.
Real Americans don’t need this.
My granddaddy took morphine in ’44 and pooped every day on raw cabbage and whiskey.
Now we got soft Americans crying because they can’t go without a $6000 pill.
Get off the drugs. Get off the pills. Get off the entitlement.
Back in my day we just held it and prayed.
And we were stronger for it.
Brian Rono
November 28, 2025 at 04:33Let’s be real - PAMORAs are the opioid industry’s PR masterpiece.
You take a drug that ruins your gut, then pay another fortune to un-ruin it.
It’s like buying a Lamborghini, then paying $20k a year to fix the brakes you broke by driving it into a wall.
And the worst part? The companies know you’ll pay.
They’ve calculated the desperation.
They know you’d rather pay $5k than quit your pain meds.
So they keep the price high, the side effects mild, and the marketing slick.
This isn’t innovation.
This is exploitation dressed in white coats.
seamus moginie
November 30, 2025 at 04:25Im from ireland and we dont have these drugs here yet
But i read this and i thought wow
My mate with cancer was on laxatives for a year and his wife had to help him with enemas every week
When he finally got methylnaltrexone he cried saying he felt human again
Its not about the money its about not being a prisoner to your own body
Why are we even arguing about cost when the alternative is suffering in silence
Someone should write a letter to the EU
They need this here too
Zac Gray
November 30, 2025 at 17:31Marjorie’s comment? That’s the one you need to read.
Not the conspiracy stuff.
Not the sarcasm.
Not the ‘get off your ass’ nonsense.
Just her.
She’s not selling you a drug - she’s telling you you’re not alone.
If you’re reading this and you’re stuck, you’re not weak.
You’re just stuck.
And there’s a way out.
Ask your doctor for PAMORAs.
Bring this post.
Ask for the patient program.
Don’t let pride or fear or cost keep you from feeling like yourself again.
You’ve earned that.
Steve and Charlie Maidment
December 2, 2025 at 16:17So if I understand correctly - we’re paying thousands to make our bowels work again after taking opioids that were prescribed to us in the first place?
Who decided this was a good business model?
And why is it that the people who need this the most - the elderly, the disabled, the poor - are the ones who can’t afford it?
It’s not just a medical issue.
It’s a moral failure.
And the fact that we’ve normalized this as ‘just the cost of pain management’?
That’s the real tragedy.
Ellen Calnan
December 3, 2025 at 01:34I used to think constipation was just… part of aging.
Until I realized it wasn’t aging - it was the opioids.
And then I realized - if I could fix the constipation without touching the pain relief - why didn’t anyone tell me this before?
It’s not about being ‘strong’ or ‘tough’.
It’s about being human.
We don’t accept that opioids make you vomit - so why do we accept that they make you stop pooping?
It’s not a side effect.
It’s a betrayal of the body’s natural rhythm.
PAMORAs don’t just help you go.
They help you breathe again.
And that’s worth every penny.