Gastroenterology / Pain Management

A Potential New Fix for Opioid-Induced Constipation

September 1, 2014
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While the majority of adverse effects linked with opioid use for pain management are short-term like nausea, sedation and itching, perhaps the most commonly experienced side-effect is also the most unremitting: constipation. Opioid-induced constipation’s mechanisms depend on opioids’ tendency to vigorously stimulate mu receptors which suppress propulsion in the colon. Counteracting an opioid’s activation of mu receptors, Naloxegol acts as a mu receptor antagonist that shows promise in reversing opioid-induced constipation. By virtue of only affecting peripheral mu receptor sites like the colon, and not central mu receptor sites like the central nervous system, Naloxegol should provide constipation-relief without triggering effects of opioid withdrawal or even lessening the strength of opioid analgesia. Two recent, randomized double-blind, placebo-controlled clinical trials indicate that naloxegol works effectively to curb opioid induced constipation. Intention-to-treat analysis shed light on statistically significant increases in bowel movement frequency over the treatment period when compared with placebo. Moreover, the drug was well tolerated, with very few demonstrated adverse effects. Should the FDA approve it, naloxegol would not be the first mu receptor antagonist available to patients: there are two currently in the market. Neither current treatment, however, provides the administrative convenience that naloxegol’s oral tablets do.


In October, 2014, naloxegol was approved by the FDA for use treating opioid-induced constipation in chronic pain patients. Suggestions for administration of the agent are as follows:

The recommended dose of naloxegol is one 25 mg tablet, taken orally once per day on an empty stomach. As such, patients should take the tablet at least one hour before or two hours after their first meal of the day. Grapefruits and grapefruit juice should not be consumed while on naloxegol. Patients should also cease taking maintenance laxatives prior to beginning naloxegol, but may resume supplementary laxative use after three days of naloxegol should constipation symptoms persist. Naloxegol is not recommended for patients with known or suspected gastrointestinal obstruction, or patients at increased risk for GI obstruction. Adverse events experienced during naloxegol treatment included abdominal pain, diarrhea and nausea. Naloxegol is cleared as a generally safe drug for up to a year of treatment time. On the market, it joins methylnaltrexone and lubiprostone as treatments for OIC. As of 2014, these has yet to be a study comparing the efficacy of the three drugs in determining which is the preferable treatment for opioid-induced constipation.