What Happens If Relistor Doesn't Work?: A Guide to Alternatives and Next Steps

October 10, 2025 •

4 min read

According to clinical data, many patients experience opioid-induced constipation (OIC) even while using conventional laxatives. For these individuals, targeted treatments like Relistor (methylnaltrexone) are an option, but what happens if Relistor doesn't work, and what are the next steps to take? This article explores potential reasons for treatment failure and outlines the comprehensive management strategy that follows, from combining medications to exploring new alternatives.

Quick Summary

This guide details the next steps to take when Relistor is not effective for opioid-induced constipation, outlining potential causes, including medical conditions or inadequate dosage. Learn about adding or switching to other laxatives, exploring different prescription alternatives, and incorporating lifestyle strategies to manage refractory OIC under medical supervision.

Key Points

Consult a healthcare provider: If Relistor is not working after 3 days, inform your doctor. They can evaluate the reason for the inadequate response, which may be related to underlying medical conditions or incorrect usage.
Reintroduce laxatives: According to prescribing guidelines, if relief is insufficient after several days on Relistor, other laxatives like osmotic (e.g., PEG) or stimulant laxatives (e.g., senna) can be used as needed.
Explore other PAMORAs: Alternatives within the same class as Relistor include Movantik (naloxegol) and Symproic (naldemedine). Each has a similar mechanism but different formulations, which may lead to a different response.
Consider other drug classes: Beyond PAMORAs, intestinal secretagogues like lubiprostone (Amitiza) offer another therapeutic option by increasing intestinal fluid secretion.
Reinforce lifestyle changes: Maintain a diet high in fiber, ensure adequate fluid intake, and engage in regular, gentle exercise to support bowel function alongside medication.
Watch for serious side effects: Immediate medical attention is needed for severe abdominal pain or persistent diarrhea, as these could indicate a serious gastrointestinal issue like a perforation.

Understanding Relistor and the Potential for Ineffectiveness

Relistor (methylnaltrexone) belongs to a class of medications called peripherally acting mu-opioid receptor antagonists (PAMORAs). It works by selectively blocking opioid receptors located in the gastrointestinal (GI) tract, which are responsible for slowing down gut motility and causing constipation. By acting peripherally, Relistor is designed to counteract the constipating effects of opioids without interfering with their pain-relieving effects in the central nervous system.

While effective for many, Relistor doesn't provide relief for every patient. When a patient experiences an inadequate response, it's crucial to understand the possible reasons before determining the next course of action.

Why Relistor May Not Work

An inadequate response to Relistor is not a sign of complete treatment failure but an indication that other factors are at play. These factors can include:

Non-opioid related constipation: Relistor is specifically for constipation caused by opioids. If other medical conditions, dietary habits, or non-opioid medications are contributing to or causing the constipation, Relistor's targeted mechanism won't address these issues.
Underlying GI pathology: Conditions that affect the structural integrity of the intestinal wall, such as Crohn's disease, diverticulitis, or certain gastrointestinal cancers, may lead to an inadequate response and can even increase the risk of serious complications like GI perforation.
Other medical problems: Severe kidney or liver disease can affect how the body processes methylnaltrexone, potentially reducing its effectiveness. Patients with these conditions require careful dose management.
Incorrect usage or timing: To work optimally, oral Relistor must be taken on an empty stomach at least 30 minutes before the first meal of the day. Skipping doses or improper timing can compromise its effectiveness.
Severe baseline OIC: For some patients with long-standing or severe opioid-induced constipation, Relistor alone may not be sufficient, and a multi-pronged approach may be necessary.

The Stepwise Management of Refractory OIC

If a patient has an inadequate response to Relistor, the next steps are typically guided by a healthcare provider. The standard approach involves adding or switching therapies in a systematic way.

Combining Relistor with Other Laxatives

Initial guidelines for starting Relistor recommend discontinuing other laxatives. However, if there is an insufficient response after a specified period (often 3 days), adding back an oral laxative is the standard next step.

Osmotic laxatives: These draw water into the colon to soften the stool and promote bowel movements. Polyethylene glycol (PEG) is often the preferred osmotic agent due to its strong evidence base and tolerability.
Stimulant laxatives: These work by stimulating the intestinal muscles to produce a bowel movement. Examples include senna or bisacodyl. They are typically reserved for occasional use or when other options fail due to potential for cramping.

Exploring Alternative PAMORAs

If a combination therapy proves insufficient, a physician might consider switching to another PAMORA. While all PAMORAs share a similar mechanism of action, minor differences in their chemical structure and pharmacokinetics can lead to different patient responses.


Attribute	Relistor (methylnaltrexone)	Movantik (naloxegol)	Symproic (naldemedine)
Mechanism	Peripherally acting mu-opioid receptor antagonist (PAMORA)	PEG-derivative of naloxone; PAMORA	Structurally related to naltrexone; PAMORA
Formulation	Oral tablet and subcutaneous injection	Oral tablet	Oral tablet
Key Differences	Available in both oral and injectable forms. Injection can provide a faster response.	Oral-only formulation. Must be taken on an empty stomach.	Oral-only formulation. Can be taken with or without food.
Common Side Effects	Abdominal pain, diarrhea, nausea, flatulence.	Abdominal pain, diarrhea, nausea, vomiting, headache.	Abdominal pain, diarrhea, nausea, gastroenteritis.

Intestinal Secretagogues

Another class of prescription medication for refractory OIC is intestinal secretagogues, which work differently from PAMORAs. Lubiprostone (Amitiza) is a chloride channel activator that increases fluid secretion into the intestinal lumen, thereby softening stool and speeding up transit. It is an FDA-approved option for OIC in adults with chronic non-cancer pain.

Lifestyle and Non-Pharmacological Interventions

As a foundational component of OIC management, lifestyle changes should always be reinforced, even when on prescription medications.

Diet and fiber: A diet rich in high-fiber foods, combined with adequate fluid intake, is essential. Water-soluble fiber supplements like psyllium may be recommended to avoid bloating associated with insoluble fibers.
Exercise: Regular physical activity, even gentle walking, can stimulate bowel movements.
Biofeedback: For patients with specific pelvic floor issues, biofeedback therapy can help retrain the muscles involved in defecation.

When to Seek Emergency Medical Attention

While addressing refractory OIC, it is critical for patients to recognize signs of a more severe issue, particularly gastrointestinal perforation. Stop taking Relistor and seek emergency medical help immediately if you experience:

Severe, persistent, or worsening abdominal pain.
Severe or persistent diarrhea.

Conclusion

While the failure of Relistor to alleviate opioid-induced constipation can be frustrating, it is not a dead end. A structured, stepped-care approach guided by a healthcare provider can effectively address the problem. By investigating the underlying cause, potentially combining Relistor with traditional laxatives, or switching to an alternative prescription medication like Movantik, Symproic, or a secretagogue like Amitiza, patients can find relief. Combining these strategies with consistent lifestyle modifications offers the best chance for successful management. Always prioritize open communication with your medical team to ensure the safest and most effective treatment plan.

Frequently Asked Questions

If you are taking oral Relistor, you should notify your healthcare provider if you have not had a bowel movement after three days of treatment. For the injection, the response is often quicker, but you should discuss continued lack of effect with your doctor.

Yes, if Relistor alone is not providing adequate relief after the initial few days of treatment, other laxatives can be resumed as needed under medical supervision. The initial instruction is to stop other laxatives when starting Relistor, but this may be adjusted based on your response.

While all three are PAMORAs that act on the gut, they differ in formulation and certain usage guidelines. Relistor is available as a tablet and injection, while Movantik and Symproic are oral tablets only. Dosage, administration timing relative to meals, and specific patient populations for which they are approved can also vary.

Yes. Relistor targets opioid-induced constipation, but other factors like dietary fiber intake, hydration levels, activity, or other medical conditions (e.g., GI disorders) can cause or worsen constipation. If Relistor fails, a full medical evaluation is needed to rule out other causes.

Yes. Intestinal secretagogues, such as lubiprostone (Amitiza), are a different class of medication approved for treating OIC. These work by increasing intestinal fluid secretion, providing another option for patients who do not respond to PAMORAs.

You should seek emergency medical help immediately if you experience severe, persistent, or worsening abdominal pain or develop severe or persistent diarrhea, as these can be signs of a serious intestinal complication.

Lifestyle interventions are an important part of managing chronic constipation. Increasing fiber and fluid intake, getting regular exercise, and establishing a regular toileting routine can all support bowel function and should be pursued in parallel with pharmacological treatments.