Naloxegol is a new agent approved for the treatment of refractory opioid-induced constipation (OIC). The incidence of OIC is difficult to assess. However, it has been reported to affect up to 95% of patients treated with opioids. While patients experiencing OIC have numerous laxative options, approximately half of these patients do not achieve satisfactory relief.

Unlike the symptomatic treatment offered by laxatives, naloxegol is able to specifically target the cause of OIC. Naloxegol works as a peripherally acting µ-opioid receptor antagonist (PAMORA). The other PAMORA available in Australia is the injectable agent, methylnaltrexone. Naloxegol, a pegylated derivative of naloxone, is administered orally. The process of pegylation reduces the membrane permeability of naloxegol and, therefore, its access to the central nervous system (CNS). As the action of naloxegol is confined to the periphery, significant changes to opioid doses are not expected to be required. Clinical trials did exclude patients with known disruptions of the blood-brain barrier such as primary brain malignancies, CNS metastases, recent brain injury, or advanced Alzheimer’s disease. Caution should be exercised before prescribing in these patient groups as they may be more prone to symptoms of opioid withdrawal or reversal of analgesia.

The most common adverse effects reported during naloxegol therapy were restricted to the gastrointestinal tract and included abdominal pain, diarrhoea, nausea, and vomiting. Gastrointestinal perforation has been reported with the use of PAMORAs in advanced disease. For this reason, it is contraindicated in patients with gastrointestinal obstruction or patients with malignancies that confer a higher risk of gastrointestinal perforation. Naloxegol should not be administered with medications that are strong inhibitors of cytochrome P450 3A4.

References:

  1. Chey WD, Webster L, Sostek M, Lappalanen J, Barker P, Tack J. Naloxegol for opioid-induced constipation in patients with noncancer pain. N Engl J Med. 2014; 370: 2387-96.
  2. Kumar L, Barker C, Emmanuel A. Opioid-induced constipation: pathophysiology, clinical consequences, and management. Gastroenterol Res Pract. 2014; 2014: 141737.
  3. Movantik(naloxegol) Australian approved product information. North Ryde: Astra Zeneca. Approved January 2016.

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