Relistor: Uses, Dosage & Side Effects
A peripheral mu-opioid receptor antagonist (PAMORA) for the treatment of opioid-induced constipation in adults when conventional laxatives have been insufficient
Relistor (methylnaltrexone bromide) is a prescription medication used to treat constipation caused by opioid pain medications in adults. It belongs to a class of drugs called peripheral mu-opioid receptor antagonists (PAMORAs), which block the constipating effects of opioids in the gut without interfering with pain relief. Relistor is administered as a subcutaneous injection and is used when conventional laxatives have not provided adequate relief.
Quick Facts
Key Takeaways
- Relistor treats constipation caused by opioid medications by selectively blocking opioid receptors in the gastrointestinal tract, without reducing pain relief or causing opioid withdrawal
- A bowel movement typically occurs within minutes to a few hours after injection – stay near a toilet when taking the medication
- Do not use Relistor if you have a known or suspected bowel obstruction, as serious complications including gastrointestinal perforation have been reported
- The standard dose is 12 mg injected subcutaneously; dosing frequency depends on whether you are receiving palliative care (every other day) or have chronic non-cancer pain (as needed, up to once daily)
- Most common side effects are abdominal pain, nausea, diarrhea, and flatulence – these are generally mild and manageable
What Is Relistor and What Is It Used For?
Relistor contains the active substance methylnaltrexone bromide, a compound that belongs to a class of medications known as peripherally acting mu-opioid receptor antagonists (PAMORAs). Opioid analgesics – medications such as morphine, oxycodone, fentanyl, and codeine – are widely prescribed for the management of moderate to severe pain. While highly effective for pain control, opioids have well-known gastrointestinal side effects, the most common and troublesome of which is constipation. This condition, known as opioid-induced constipation (OIC), occurs because opioid receptors are not only present in the brain and spinal cord (where they mediate pain relief) but also abundantly expressed throughout the gastrointestinal tract.
When opioids bind to mu-opioid receptors in the gut wall, they slow intestinal motility, reduce secretion of fluids into the intestinal lumen, and increase absorption of water from stool. The result is hard, dry stool that is difficult to pass, along with straining, a sensation of incomplete evacuation, and infrequent bowel movements. Unlike many other opioid side effects, tolerance to OIC rarely develops, meaning that the constipation often persists for as long as the patient continues opioid therapy.
Methylnaltrexone is a quaternary ammonium compound – a charged molecule that has very limited ability to cross the blood-brain barrier. This unique chemical property is the key to Relistor's therapeutic advantage: it can block opioid receptors in the peripheral tissues (primarily the gastrointestinal tract) without reaching the central nervous system in clinically meaningful amounts. As a result, Relistor relieves opioid-induced constipation without reversing the centrally mediated analgesic effects of the opioid or precipitating opioid withdrawal syndrome.
Relistor is approved for two distinct patient populations. First, it is used in adult patients receiving palliative care for advanced illness who have opioid-induced constipation that has not responded adequately to conventional laxative therapy. In this setting, it is typically used for a limited period, usually less than four months. Second, Relistor is indicated for adult patients with chronic non-cancer pain who have opioid-induced constipation that has not responded to at least one laxative. In this population, it may be used on a longer-term basis.
It is important to understand that Relistor is specifically designed to treat constipation caused by opioid medications. It should not be used for constipation that is unrelated to opioid use. Your doctor will confirm that your constipation is opioid-related before prescribing this medication.
Peripheral mu-opioid receptor antagonists (PAMORAs) represent a targeted approach to managing opioid-induced constipation. Unlike systemic opioid antagonists such as naloxone or naltrexone, which can reverse opioid analgesia and precipitate withdrawal, PAMORAs selectively block opioid receptors in the gut without affecting pain control. Methylnaltrexone (Relistor) was the first PAMORA to receive regulatory approval and remains one of the most extensively studied medications in this class.
What Should You Know Before Taking Relistor?
Contraindications
Relistor must not be used in patients with a known or suspected mechanical gastrointestinal obstruction, or in patients who are at risk for recurrent obstruction. Bowel obstruction is a condition in which the normal passage of intestinal contents is physically blocked, and administering Relistor in this setting could lead to dangerous complications, including gastrointestinal perforation (a hole forming in the bowel wall). Before starting treatment, your doctor should confirm that your constipation is not caused by a structural blockage.
You should also not use Relistor if you are allergic (hypersensitive) to methylnaltrexone bromide or to any of the other ingredients in the formulation (listed in the contents section below).
Warnings and Precautions
Cases of gastrointestinal perforation have been reported in patients using Relistor. If you develop severe, persistent, or worsening abdominal symptoms, stop taking this medication and contact your doctor immediately. Patients with conditions that may reduce the structural integrity of the gastrointestinal wall (such as peptic ulcer disease, diverticular disease, infiltrative gastrointestinal tract malignancies, or peritoneal metastases) may be at increased risk.
Before starting Relistor, tell your doctor about all of your medical conditions, especially if you:
- Have Crohn's disease or gastrointestinal ulcers: These conditions may increase the risk of gastrointestinal perforation.
- Have diverticular disease: Diverticula (small pouches in the bowel wall) may be more susceptible to perforation when bowel motility is suddenly restored.
- Have a colostomy or peritoneal catheter: Relistor should be used with caution in patients with these devices, as changes in bowel activity could affect their function.
- Have fecal impaction: Your doctor should assess and potentially treat fecal impaction before starting Relistor.
- Have severe liver or kidney disease: These conditions may affect how your body processes methylnaltrexone. Your doctor may need to adjust the dose or monitor you more closely.
It is important to be near a toilet or have assistance available, as a bowel movement can occur within 30 minutes of the injection. This rapid onset means patients should plan accordingly, particularly those with limited mobility.
Although Relistor is designed not to cross the blood-brain barrier, some patients have reported symptoms resembling opioid withdrawal shortly after injection, including feeling cold, chills, shivering, sweating, abdominal pain, and increased heart rate. If you experience these symptoms, inform your doctor. In rare cases, more clinically significant opioid withdrawal has been reported, particularly in patients with disruptions of the blood-brain barrier.
If you develop severe or persistent diarrhea (repeated watery bowel movements), you should discontinue treatment and contact your doctor immediately. Severe diarrhea can lead to dehydration and electrolyte imbalances, particularly in elderly or debilitated patients.
Children and Adolescents
Relistor should not be given to children and adolescents under 18 years of age. The safety and efficacy of methylnaltrexone have not been established in the pediatric population, and the potential risks and benefits in this age group are unknown. Opioid-induced constipation in children may require different management strategies, and a pediatric gastroenterologist should be consulted for guidance.
Pregnancy and Breastfeeding
The effects of methylnaltrexone bromide on human pregnancy are not well established. Animal reproduction studies have not demonstrated fetal harm, but animal studies are not always predictive of human outcomes. As a precaution, Relistor should only be used during pregnancy if the potential benefit to the mother clearly justifies the potential risk to the fetus. If you are pregnant or planning to become pregnant, discuss the risks and benefits of Relistor with your doctor before starting treatment.
It is not known whether methylnaltrexone is excreted in human breast milk. As a precaution, women using Relistor should not breastfeed, or should discuss with their doctor whether to discontinue breastfeeding or discontinue the medication. The decision should take into account the importance of the drug to the mother and the potential risks to the nursing infant.
Driving and Operating Machinery
Dizziness is a common side effect of Relistor. If you experience dizziness after injection, do not drive or operate heavy machinery until the symptoms have resolved. Patients should be aware that the onset of bowel activity may also make it impractical to drive or be away from a toilet for a period following injection.
Important Information About Ingredients
Relistor contains less than 1 mmol (23 mg) of sodium per dose, meaning it is essentially sodium-free. This is relevant for patients who are on a sodium-restricted diet. The solution also contains sodium chloride, sodium calcium edetate, glycine hydrochloride, water for injections, hydrochloric acid, and sodium hydroxide (for pH adjustment).
How Does Relistor Interact with Other Drugs?
One of the practical advantages of Relistor is its relatively favorable drug interaction profile. Because methylnaltrexone acts primarily at peripheral opioid receptors in the gastrointestinal tract and has limited systemic absorption compared to oral medications, the potential for systemic drug-drug interactions is lower than with many other therapeutic agents.
However, certain interactions should be considered before and during treatment with Relistor. In clinical studies and post-marketing experience, the following potential interactions have been identified:
| Drug / Drug Class | Nature of Interaction | Clinical Significance |
|---|---|---|
| Other opioid antagonists (naloxone, naltrexone, alvimopan) | Additive opioid receptor antagonism; increased risk of opioid withdrawal and reduced analgesia | Avoid concomitant use |
| Strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine, bupropion) | May increase plasma levels of methylnaltrexone by inhibiting its partial metabolic pathway | Use with caution; monitor for increased side effects |
| Opioid analgesics (morphine, oxycodone, fentanyl, codeine, hydromorphone) | No effect on central opioid analgesia; selectively blocks peripheral opioid effects | Safe to use together (this is the intended co-administration) |
| Laxatives (docusate, senna, lactulose, polyethylene glycol) | Additive laxative effects; potential for increased diarrhea | Your doctor will advise on continuing or adjusting laxatives |
| Methadone | No clinically significant pharmacokinetic interaction demonstrated in studies | No dose adjustment needed |
It is essential to inform your doctor or pharmacist about all medications you are taking, including prescription drugs, over-the-counter medicines, herbal supplements, and vitamins. While Relistor has a limited interaction profile, comprehensive medication review ensures the safest and most effective treatment plan for your individual circumstances.
Your doctor may allow you to continue taking other medications for constipation, such as laxatives, while using Relistor. However, the decision to continue, adjust, or stop other laxatives should be made by your prescribing physician based on your clinical response to Relistor.
Unlike systemic opioid antagonists (naloxone, naltrexone) which can reverse opioid analgesia and precipitate withdrawal, Relistor is specifically designed to be used safely alongside opioid pain medications. Its inability to cross the blood-brain barrier in clinically significant amounts means that patients can continue to receive full pain relief while treating their opioid-induced constipation.
What Is the Correct Dosage of Relistor?
Relistor should always be used exactly as your doctor has prescribed. The medication is administered as a subcutaneous (under the skin) injection. The correct dose and dosing schedule depend on your specific clinical situation and the reason for your opioid therapy. Do not change the dose or dosing frequency without consulting your doctor.
Adults with Chronic Non-Cancer Pain
For adult patients with chronic non-cancer pain who have opioid-induced constipation that has not responded to laxative therapy, the recommended dose is:
| Parameter | Recommendation |
|---|---|
| Dose | 12 mg (0.6 mL solution) |
| Route | Subcutaneous injection |
| Frequency | As needed, minimum 4 times per week, maximum once daily (7 times per week) |
| Injection sites | Thigh, abdomen (stomach), or upper arm (if administered by another person) |
Adults Receiving Palliative Care
For patients receiving palliative care for advanced illness, the dose is weight-based and administered every 48 hours (every other day):
| Body Weight | Dose | Volume | Frequency |
|---|---|---|---|
| 38–61 kg | 8 mg | 0.4 mL | Every 48 hours (every other day) |
| 62–114 kg | 12 mg | 0.6 mL | Every 48 hours (every other day) |
For patients outside the 38–114 kg weight range, the dose is calculated at 0.15 mg/kg. Your doctor will determine the appropriate dose and volume. In palliative care settings, Relistor is typically used for a limited period, usually less than 4 months.
How to Administer the Injection
Relistor is given as a subcutaneous injection into one of three recommended areas: (1) the front of the thigh, (2) the abdomen (avoiding the area around the navel), or (3) the back of the upper arm (only if another person is giving the injection). Rotate injection sites with each dose to minimize injection site reactions. Before your first self-injection, your doctor, nurse, or pharmacist will train you on the correct technique.
Key points for injection preparation and administration:
- Inspect the solution: Before use, check that the solution is clear, colorless to slightly yellow, and free of particles or flakes. Do not use if the solution appears cloudy or discolored.
- Prepare the injection site: Clean the chosen area with an alcohol swab and allow it to dry. Do not inject into skin that is tender, bruised, red, hard, scarred, or has stretch marks.
- Draw up the correct dose: Follow the instructions provided with your syringe to draw the prescribed volume (0.4 mL for 8 mg or 0.6 mL for 12 mg).
- Inject at a 45-degree angle: Gently pinch the cleaned skin, insert the needle at a slight angle (45 degrees), and slowly push the plunger until the syringe is empty.
- Dispose safely: Place the used syringe immediately into an approved sharps container. Never reuse needles or syringes.
You may experience a bowel movement within minutes to a few hours after injection. Ensure you have access to a toilet or bedpan.
Missed Dose
If you forget to take a dose, contact your doctor or pharmacist as soon as possible for guidance. Do not take a double dose to make up for a missed dose.
Overdose
If you have used more Relistor than prescribed – either by injecting too much at one time or by using more than one injection in 24 hours – you may experience dizziness upon standing (orthostatic hypotension). Contact your doctor or pharmacist immediately. Take the outer packaging of the medication with you, even if it is empty, to help healthcare providers identify what was taken.
Stopping Treatment
Do not stop using Relistor without first consulting your doctor. If your opioid therapy is discontinued, there is no need to continue Relistor since the cause of the constipation will have been removed. Your doctor will advise you on when and how to stop treatment safely.
What Are the Side Effects of Relistor?
Like all medicines, Relistor can cause side effects, although not everyone who takes it will experience them. The side effect profile of methylnaltrexone has been well characterized through multiple randomized controlled trials and post-marketing surveillance. The majority of reported adverse effects are gastrointestinal in nature, which is expected given the drug's mechanism of action in restoring bowel motility.
The most important safety concern with Relistor is the risk of gastrointestinal perforation, which has been reported in post-marketing experience. Although the frequency of this complication cannot be precisely estimated from available data, it is a potentially life-threatening event. Patients with conditions that compromise the structural integrity of the gastrointestinal wall (such as advanced malignancy involving the bowel, peptic ulcer disease, diverticular disease, or peritoneal metastases) may be at increased risk.
Very Common
May affect more than 1 in 10 people
- Abdominal pain (stomach pain)
- Nausea (feeling sick)
- Diarrhea (frequent watery bowel movements)
- Flatulence (gas/bloating)
Common
May affect up to 1 in 10 people
- Dizziness
- Opioid withdrawal-like symptoms (feeling cold, chills/shivering, runny nose, sweating, goosebumps, flushing, rapid heartbeat)
- Injection site reactions (stinging, burning, pain, redness, swelling)
- Vomiting
Not Known
Frequency cannot be estimated from available data
- Gastrointestinal perforation (a hole in the bowel wall) – seek immediate medical attention if you develop severe or persistent abdominal pain
The gastrointestinal side effects (abdominal pain, nausea, diarrhea, flatulence) are a direct consequence of the pharmacological action of Relistor. By blocking opioid receptors in the gut and restoring normal bowel motility, the transition from a constipated state to normal or increased bowel activity can be accompanied by cramping, loose stools, and gas. These effects are typically most pronounced during the initial doses and tend to diminish over time as the bowel adjusts.
Injection site reactions are generally mild to moderate in severity and include stinging, burning, pain, redness, and localized swelling at the injection site. Rotating injection sites between administrations can help minimize these reactions. If you develop signs of infection at an injection site (increasing redness, warmth, swelling, or discharge), contact your healthcare provider.
Opioid withdrawal-like symptoms have been reported in some patients shortly after Relistor administration. These symptoms may include feeling cold, chills, shivering, sweating, goosebumps, flushing, and rapid heartbeat. In most cases, these symptoms are mild, transient, and do not represent true systemic opioid withdrawal. However, if symptoms are severe or persist, inform your doctor, as dose adjustment or discontinuation may be necessary.
Stop taking Relistor and contact your doctor or go to the nearest emergency department immediately if you experience severe abdominal pain that does not go away or gets worse. This could be a symptom of gastrointestinal perforation, which requires urgent medical treatment. Also seek immediate medical attention if you develop severe or persistent diarrhea, signs of dehydration (extreme thirst, decreased urination, dry mouth), or symptoms of severe opioid withdrawal.
How Should You Store Relistor?
Proper storage of Relistor ensures the medication remains safe and effective throughout its shelf life. Follow these storage guidelines carefully:
- Keep out of sight and reach of children: Store in a secure location where children cannot access the medication.
- Check the expiration date: Do not use Relistor after the expiration date printed on the carton and vial label after “EXP.” The expiration date refers to the last day of the stated month.
- No special temperature requirements: Relistor does not require refrigeration and can be stored at room temperature.
- Protect from light: Keep the vial in the outer carton to protect it from light exposure, which can degrade the active ingredient.
- Inspect before use: Before each injection, visually inspect the solution. It should be clear, colorless to slightly yellow, and free from flakes or particles. Do not use if the solution appears cloudy, discolored, or contains visible particles.
- Use within 24 hours once drawn up: If the solution has been drawn into a syringe, it must be used within 24 hours because Relistor is sensitive to light and may lose its effectiveness if left in the syringe for longer periods.
- Proper disposal: Do not dispose of medications in wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. These measures help protect the environment.
What Does Relistor Contain?
Active Ingredient
The active substance is methylnaltrexone bromide. Each 0.6 mL vial contains 12 mg of methylnaltrexone bromide. One milliliter of the injection solution contains 20 mg of methylnaltrexone bromide. Methylnaltrexone is a quaternary ammonium derivative of naltrexone, specifically modified to prevent crossing of the blood-brain barrier while retaining its opioid receptor antagonist activity at peripheral sites.
Inactive Ingredients (Excipients)
| Ingredient | Role | Notes |
|---|---|---|
| Methylnaltrexone bromide | Active substance (PAMORA) | 12 mg per 0.6 mL vial |
| Sodium chloride | Tonicity agent (isotonic adjustment) | Ensures compatibility with body fluids |
| Sodium calcium edetate | Chelating agent (stabilizer) | Prevents metal-catalyzed degradation |
| Glycine hydrochloride | Buffer (pH stabilizer) | Maintains solution pH |
| Water for injections | Solvent | Volume to 0.6 mL |
| Hydrochloric acid / Sodium hydroxide | pH adjusters | Ensure correct pH for injection |
Appearance and Pack Sizes
Relistor is supplied as a clear, colorless to slightly yellow solution for injection in single-use glass vials. Each vial contains 0.6 mL of injection solution. Packs containing more than one vial include inner packs consisting of: one vial, one 1 mL syringe with retractable needle, and two alcohol swabs. Available pack sizes are 1 vial, 2 vials (with 2 syringes and 4 alcohol swabs), and 7 vials (with 7 syringes and 14 alcohol swabs). Not all pack sizes may be marketed in every country.
Marketing Authorization Holder and Manufacturer
The marketing authorization holder is Bausch Health Ireland Limited, Dublin, Ireland. Relistor is manufactured by Bausch Health Poland Sp. z o.o. in Mysłowice, Poland. Relistor has been approved by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), among other regulatory authorities worldwide.
Frequently Asked Questions About Relistor
Relistor (methylnaltrexone bromide) is used to treat opioid-induced constipation (OIC) in adults. It is specifically designed for patients who are taking opioid pain medications (such as morphine, oxycodone, fentanyl, or codeine) and who have not had adequate relief from conventional laxatives. Relistor blocks the constipating effects of opioids on the gut without reversing their pain-relieving effects. It is approved for use in both palliative care patients with advanced illness and patients with chronic non-cancer pain.
Relistor can work very quickly. A bowel movement can occur within minutes to a few hours after the injection. In clinical trials, approximately 50% of palliative care patients had a bowel movement within 4 hours of their first dose, and the median time to first bowel movement was approximately 30–60 minutes. Because of this rapid onset, it is essential to be near a toilet or have access to a bedpan when the injection is given.
No. Relistor is specifically designed to act only on opioid receptors in the gastrointestinal tract and other peripheral tissues. Because methylnaltrexone is a quaternary amine (a positively charged molecule), it has very limited ability to cross the blood-brain barrier. This means it does not interfere with the pain-relieving effects of opioids, which are mediated through opioid receptors in the brain and spinal cord. Clinical trials confirmed that patients using Relistor maintained their opioid analgesia and did not require dose increases in their pain medications.
Yes, Relistor can be self-administered at home after you have been trained by your doctor, nurse, or pharmacist on the correct injection technique. The injection is given subcutaneously (under the skin) into the thigh, abdomen (avoiding the navel area), or the back of the upper arm (if someone else is giving the injection). Before attempting self-injection, make sure you understand how to prepare the syringe, select and clean the injection site, administer the injection, and safely dispose of used materials. Always rotate injection sites to minimize reactions.
If you develop severe or persistent diarrhea (repeated watery bowel movements), you should stop taking Relistor and contact your doctor immediately. Severe diarrhea can lead to dehydration and electrolyte imbalances, which can be particularly dangerous in elderly, debilitated, or seriously ill patients. Stay well hydrated by drinking fluids. Your doctor will assess whether Relistor can be restarted at a later time or whether an alternative treatment approach is needed.
No. Although both methylnaltrexone (Relistor) and naloxone are opioid receptor antagonists, they work in fundamentally different ways. Naloxone freely crosses the blood-brain barrier and reverses all opioid effects, including pain relief – this is why it is used as an emergency antidote for opioid overdose. Relistor, on the other hand, is specifically designed to stay outside the brain. It only blocks opioid receptors in the gut and peripheral tissues, which means it treats constipation without affecting pain control. They should not be used interchangeably, and combining them should be avoided as it may lead to excessive opioid antagonism.
References
- European Medicines Agency (EMA). Relistor (methylnaltrexone bromide) – Summary of Product Characteristics. Last updated 2024. Available at: EMA Relistor EPAR.
- U.S. Food and Drug Administration (FDA). Relistor (methylnaltrexone bromide) – Prescribing Information. Bausch Health US, LLC. Revised 2024.
- Thomas J, Karver S, Cooney GA, et al. Methylnaltrexone for Opioid-Induced Constipation in Advanced Illness. N Engl J Med. 2008;358(22):2332–2343. doi:10.1056/NEJMoa0707377.
- Michna E, Blonsky ER, Schulman S, et al. Subcutaneous Methylnaltrexone for Treatment of Opioid-Induced Constipation in Patients with Chronic, Nonmalignant Pain: A Randomized Controlled Study. J Pain. 2011;12(5):554–562. doi:10.1016/j.jpain.2010.11.008.
- Crockett SD, Greer KB, Heidelbaugh JJ, et al. American Gastroenterological Association Institute Guideline on the Medical Management of Opioid-Induced Constipation. Gastroenterology. 2019;156(1):218–226. doi:10.1053/j.gastro.2018.07.016.
- Argoff CE, Brennan MJ, Camilleri M, et al. Consensus Recommendations on Initiating Prescription Therapies for Opioid-Induced Constipation. Pain Med. 2015;16(12):2324–2337. doi:10.1111/pme.12937.
- Brenner DM, Stern E, Cash BD. Opioid-Related Constipation in Patients with Non-Cancer Pain Syndromes: A Review of Evidence-Based Therapies and Justification for a Change in Nomenclature. Curr Gastroenterol Rep. 2017;19(3):12. doi:10.1007/s11894-017-0555-x.
- World Health Organization (WHO). WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents. 2018. Available at: WHO Cancer Pain Guidelines.
- British National Formulary (BNF). Methylnaltrexone bromide. National Institute for Health and Care Excellence (NICE). 2025.
- Leppert W. Emerging Therapies for Patients with Symptoms of Opioid-Induced Bowel Dysfunction. Drug Des Devel Ther. 2015;9:2215–2231. doi:10.2147/DDDT.S32684.
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