Should I take Relistor (methylnaltrexone) and Trulance (plecanatide) together?

Should You Take Relistor and Trulance Together?

No, you should not routinely combine Relistor (methylnaltrexone) and Trulance (plecanatide) together, as they treat constipation through different mechanisms and are indicated for different clinical scenarios—combining them risks excessive diarrhea and is not supported by evidence.

Understanding the Medications and Their Roles

Relistor (Methylnaltrexone)

Relistor is a peripherally acting μ-opioid receptor antagonist (PAMORA) specifically designed for opioid-induced constipation (OIC) that has failed to respond to standard laxative therapy 1, 2, 3. It works by blocking opioid receptors in the gut without affecting central pain control, making it ideal for patients on chronic opioid therapy who develop constipation despite using traditional laxatives 2, 1.

• Indication: Second-line treatment for OIC after laxatives fail 1, 3
• Mechanism: Blocks peripheral opioid receptors in the gastrointestinal tract
• Onset: Most patients achieve defecation within 90 minutes of subcutaneous administration 2
• Dosing: 0.15 mg/kg subcutaneously every other day (maximum once daily) 1

Trulance (Plecanatide)

Trulance is a guanylate cyclase-C agonist that enhances intestinal fluid secretion 4, 5. It is FDA-approved for chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) 5, 6.

• Indication: First or second-line treatment for CIC or IBS-C 4, 7
• Mechanism: Increases intestinal secretions to soften stool
• Dosing: 3 mg once daily 5
• Common side effect: Diarrhea (4.3% vs 1.0% placebo) 6

Why Not Combine Them?

Different Clinical Indications

The medications target fundamentally different constipation types:

• Relistor is specifically for constipation caused by opioids in patients already on laxatives 1, 2, 3
• Trulance is for non-opioid-related constipation (CIC or IBS-C) 4, 5

Risk of Excessive Diarrhea

Both medications can cause diarrhea as a side effect:

• Trulance causes diarrhea in approximately 4% of patients 6
• Combining two pro-motility/secretory agents significantly increases this risk
• The FDA label for Trulance warns to stop the medication if severe diarrhea develops 5

Lack of Evidence for Combination

No guideline or study supports combining these medications [1-7]. The NCCN Palliative Care guidelines mention that lubiprostone (a similar secretagogue) "could be used in combination with a peripherally acting μ-opioid receptor antagonist such as methylnaltrexone" 1, but this is theoretical and not standard practice.

The Correct Treatment Algorithm

For Opioid-Induced Constipation:

1. First-line: Prophylactic stimulant laxative (senna) with or without stool softener when starting opioids 1, 8, 1
2. If constipation persists: Add bisacodyl, polyethylene glycol, lactulose, or magnesium-based laxatives 1
3. If laxative-refractory: Add Relistor (methylnaltrexone) 1, 2, 3
4. Never use Trulance for OIC—it is not indicated and PAMORAs are the evidence-based choice 3

For Chronic Idiopathic Constipation or IBS-C:

1. First-line: Lifestyle modifications plus osmotic laxatives (PEG) or stimulant laxatives 7
2. Second-line: Secretagogues like Trulance (plecanatide), linaclotide, or lubiprostone 4, 7
3. Never add Relistor—it only works for opioid-induced constipation 3

Critical Pitfalls to Avoid

Do not use Trulance if:

• The patient has a bowel obstruction 5
• The patient is under 6 years old (contraindicated due to severe diarrhea risk) 5
• The patient is 6-17 years old (not recommended) 5

Do not use Relistor if:

• The patient has postoperative ileus or mechanical bowel obstruction 1
• The patient is not on chronic opioid therapy (it won't work) 2, 3

When Might You See Both Medications?

The only scenario where a patient might theoretically be on both is if they have:

1. Baseline CIC or IBS-C already being treated with Trulance, AND
2. Newly started opioid therapy causing additional constipation requiring Relistor

However, even in this rare situation, the appropriate approach would be to:

• Optimize one medication first before adding another
• Consider stopping Trulance and managing with laxatives plus Relistor if opioids are the dominant cause
• Closely monitor for diarrhea if both are absolutely necessary

The evidence strongly supports using these medications separately based on the underlying cause of constipation, not in combination [1-9].