What Does Naloxegol Do? A Comprehensive Look at the Medication

October 6, 2025 •

3 min read

Opioid-induced constipation (OIC) is the most common side effect experienced by patients on chronic opioid therapy, affecting up to 90% of individuals. Naloxegol, a peripherally acting mu-opioid receptor antagonist (PAMORA), is a medication specifically designed to counteract the constipating effects of opioids without impacting their central pain-relieving effects.

Quick Summary

Naloxegol treats opioid-induced constipation by blocking opioid receptors in the gastrointestinal tract. This targeted action restores normal bowel function while preserving central pain relief. It is taken as an oral tablet on an empty stomach.

Key Points

Targeted Action: Naloxegol is a peripherally acting mu-opioid receptor antagonist (PAMORA) that blocks opioid receptors specifically in the gastrointestinal tract.
Preserves Pain Relief: By not crossing the blood-brain barrier, naloxegol prevents constipation without reversing the central pain-relieving effects of opioid medication.
Treats Opioid-Induced Constipation (OIC): It is used in adults with chronic, non-cancer pain whose OIC has not responded adequately to traditional laxatives.
Taken on an Empty Stomach: To prevent increased absorption and side effects, naloxegol should be taken once daily on an empty stomach, at least one hour before or two hours after a meal.
Common Side Effects: The most frequent side effects are gastrointestinal, including abdominal pain, diarrhea, and nausea.
Drug Interactions: Strong CYP3A4 inhibitors (e.g., clarithromycin, grapefruit juice) are contraindicated, and caution is needed with other medications that affect this enzyme pathway.
Rapid Onset: Clinical trials show a median time to first spontaneous bowel movement often occurs within hours of the first dose for many patients.
Withdrawal Risk: Although rare, opioid withdrawal symptoms can occur, particularly in patients with a compromised blood-brain barrier or those taking methadone.

The Mechanism Behind How Naloxegol Works

Opioids bind to mu-opioid receptors in both the brain and the gastrointestinal (GI) tract. This binding in the GI system leads to reduced intestinal movement and decreased fluid secretion, causing constipation. Traditional laxatives often do not adequately address this issue.

Naloxegol (Movantik) is a peripherally acting mu-opioid receptor antagonist (PAMORA) that targets opioid receptors outside the brain and central nervous system. It is a modified form of naloxone with a polyethylene glycol (PEG) molecule attached, which prevents it from crossing the blood-brain barrier. By blocking GI opioid receptors, naloxegol counteracts opioid-induced constipation, restoring normal bowel function without affecting the opioid's central pain relief.

Therapeutic Use: Who Needs Naloxegol?

Naloxegol is prescribed for adults with chronic non-cancer pain experiencing opioid-induced constipation that hasn't responded to traditional laxatives. It is used for patients on a stable opioid dose for conditions like chronic back pain. Some areas may also use it for cancer-related pain. Studies show naloxegol effectively and rapidly improves OIC symptoms.

How Naloxegol is Taken

Naloxegol should be taken once daily on an empty stomach, either at least 1 hour before the first meal or 2 hours after. This timing helps prevent increased absorption, which could raise the risk of side effects. The tablet can be crushed and mixed with water if needed. If opioid medication is stopped, naloxegol should also be discontinued.

Potential Side Effects and Drug Interactions

Naloxegol can cause side effects, usually mild, but some may be serious.

Common side effects include:

Gastrointestinal: Abdominal pain, diarrhea, nausea, vomiting, flatulence.
Other: Headache.
Rare: Opioid withdrawal symptoms like anxiety or chills, especially in those with a compromised blood-brain barrier or taking methadone.

Serious rare side effects include severe abdominal pain or allergic reactions. There's also a rare risk of GI perforation in patients with certain pre-existing conditions.

Important Drug and Food Interactions

CYP3A4 Inhibitors: Strong inhibitors (e.g., ketoconazole, clarithromycin, grapefruit juice) are not to be used with naloxegol due to increased side effect risk. Moderate inhibitors may require dose adjustment.
CYP3A4 Inducers: Strong inducers (e.g., rifampin, St. John's wort) can reduce naloxegol's effectiveness.
Other Opioid Antagonists: Avoid combining naloxegol with other opioid antagonists to prevent opioid withdrawal.

How Naloxegol Compares to Other Treatments

Treatment options for opioid-induced constipation include traditional laxatives and PAMORAs like naloxegol.

Comparison Table: Naloxegol vs. Traditional Laxatives


Feature	Naloxegol (PAMORA)	Traditional Laxatives (e.g., osmotic, stimulant)
Mechanism of Action	Blocks mu-opioid receptors in the GI tract.	Increase colon water or stimulate muscle contractions.
Efficacy in OIC	High, especially when laxatives fail.	Often insufficient for chronic OIC.
Onset of Action	Rapid, often within 24 hours.	Can take hours to days.
Impact on Analgesia	Preserves central pain relief.	No impact, but often ineffective for OIC.
Side Effects	GI issues common; rare withdrawal risk.	Can cause cramping, bloating; chronic use risks electrolyte issues.
Cost	Typically higher.	Generally less expensive.

Conclusion

Naloxegol is an effective oral treatment for opioid-induced constipation in adults with chronic non-cancer pain. As a PAMORA, it selectively blocks opioid receptors in the gut, alleviating constipation without interfering with the opioid's pain relief in the brain. It is a valuable second-line option for patients whose OIC doesn't respond to traditional laxatives. Taking it on an empty stomach and being aware of drug interactions are important for safe use. Naloxegol can provide rapid relief and improve the quality of life for patients on long-term opioid therapy.

Resources

For further information on naloxegol and opioid-induced constipation, the National Institutes of Health (NIH) provides extensive data through its NCBI Bookshelf.

Frequently Asked Questions

The primary function of naloxegol is to treat opioid-induced constipation (OIC) in adults with chronic, non-cancer pain. It works by targeting and blocking the opioid receptors in the gastrointestinal tract that cause constipation, without interfering with the opioid's central pain-relieving effects.

Naloxegol can work relatively quickly. In clinical studies, many patients reported a first spontaneous bowel movement (SBM) within 24 hours of their first dose. The median time to first SBM was significantly faster with naloxegol compared to placebo.

It is recommended to stop taking other maintenance laxatives before starting naloxegol. However, if adequate relief is not achieved after 3 days of naloxegol treatment, a doctor may advise restarting other laxatives as needed.

Naloxegol is a modified version of naloxone, but their primary uses are different. Naloxegol is engineered to act only on peripheral opioid receptors, specifically to treat opioid-induced constipation without affecting the central nervous system. Naloxone, on the other hand, rapidly reverses all opioid effects, both central and peripheral, and is used to treat opioid overdose.

Patients taking methadone may have a higher risk of experiencing gastrointestinal side effects like stomach pain and diarrhea with naloxegol. It is important to discuss any concerns with a doctor, who will determine if naloxegol is a safe option and may start with a lower dose.

If you miss a dose of naloxegol, take it as soon as you remember. If it is almost time for your next scheduled dose, skip the missed one and continue with your regular schedule. Do not take a double dose to make up for a missed one.

The most common side effects include abdominal pain, diarrhea, nausea, gas, and headache. These are typically mild to moderate and often occur early in treatment.