Naloxegol is a peripherally acting opioid antagonist which is used to treat constipation caused by chronic opioid use for noncancer pain. Naloxegol has not been linked to serum enzyme elevations during therapy or to clinically apparent liver injury.


Naloxegol (nal ox' ee gol) is a pegylated, semisynthetic opiate receptor antagonist which is similar structurally to naltrexone, but is peripherally restricted and thus has few if any effects on the central nervous system. Naloxegol is a polyethylene glycol (PEG) derivative of alpha-naloxol, an opiate antagonist. The addition of the large PEG molecule to naloxol does not block its engagement with opioid receptors, but does prevent the drug from crossing the blood brain barrier. As a consequence, the opioid antagonist reverses the peripheral but not the central nervous system effects of opiates, such as pain relief and euphoria. In large, preregistration trials, naloxegol was found to increase spontaneous bowel movement frequency and reduce constipation related side effects of opiates used for analgesia in patients with chronic pain. Naloxegol was approved for use in the United States in 2014 and is available as tablets of 12.5 and 25 mg under the brand name Movantik. The recommended dosage is 25 mg once daily, reducing the dose to 12.5 mg daily for intolerance. Side effects include abdominal pain, diarrhea, nausea, flatulence, anxiety, restlessness and sweating. Withdrawal symptoms can occur, but are rare. In persons not taking opioids, naloxegol has minimal effects on constipation. Rare but potentially severe adverse events include withdrawal symptoms, hypersensitivity reactions and gastrointestinal perforation.


Therapy with naloxegol has not been linked to serum enzyme elevations or to clinically apparent liver injury. In preregistration studies, liver test abnormalities arose in less than 1% of treated patients but were transient, mild and not associated with symptoms. There were no reported cases of liver injury with jaundice or symptoms. Since its approval and more widescale use, there have been no published reports of hepatotoxicity attributed to naloxegol.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Mechanism of Injury

The mechanism by which naloxegol might cause liver injury is not known. Naloxegol is extensively metabolized in the liver, largely by CYP 3A4 and it is susceptible to drug-drug interactions with agents that induce or inhibition CYP 3A activity. Most opioid-antagonists appear to have little intrinsic hepatotoxicity.

Drug Class: Gastrointestinal Agents, Cathartics and Laxatives; Opioid Antagonists; Substance Abuse Treatment Agents

Other Drugs in the Class: Nalmefene, Naloxone, Naltrexone



Naloxegol – Movantik®


Opioid Antagonists


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 20 March 2020

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    (Expert review of hepatotoxicity published in 1999; mentions that trials of naltrexone have reported serum aminotransferase elevations in up to 30% of recipients, an effect that appeared to be partially dose dependent; naloxegol not discussed).
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    (Review of hepatotoxicity discusses buprenorphine, an orally available morphine analogue, which has been linked to cases of severe acute liver injury, usually as a result of intravenous administration; naloxegol not discussed).
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    (Among 207 patients with opioid-use related constipation treated with naloxegol [5, 25 or 50 mg once daily] or placebo for 4 weeks, spontaneous bowel movements increased with higher doses of naloxegol, while side effects included abdominal pain, diarrhea and nausea, but there were “no clinically relevant changes in serum chemistry”).
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    (Among 1362 patients with opioid induced constipation treated in two controlled trials with naloxegol [12.5 or 25 mg daily] or placebo, spontaneous bowel movements were more frequent with naloxegol, particularly with a 25 mg dose, and adverse events were largely mild gastrointestinal intolerance without change in pain scores or opioid dose; no mention of ALT elevations or hepatotoxicity, but there were no liver related serious adverse events).
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  • Webster L, Tummala R, Diva U, Lappalainen J. A 12-week extension study to assess the safety and tolerability of naloxegol in patients with noncancer pain and opioid-induced constipation. J Opioid Manag. 2016;12:405–19. [PubMed: 28059433]
    (Among 302 patients participating in an extension study of naloxegol for opioid induced constipation, adverse events were more common with the higher dose (25 mg daily: 41%) vs lower dose (12.5 mg daily: 34%) vs placebo (31%), but serious adverse events were similar (5% vs 6%) and there was no mention of ALT elevations or hepatotoxicity).
  • Nalamachu S, Gudin J, Datto C, Coyne K, Poon JL, Hu Y. Efficacy and safety of naloxegol for opioid-induced constipation assessed by specific opioid medication, opioid dose, and duration of opioid use. J Opioid Manag. 2018;14:211–21. [PubMed: 30044486]
    (Among 1337 adults with opioid induced constipation treated with naloxegol (12.5 or 25 mg) or placebo once daily for 12 weeks, adverse event rates were similar (52% and 64% vs 51%); no mention of ALT elevations or hepatotoxicity).
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