Naloxegol is a pegylated derivative of naloxone and is a neutral antagonist of the µ-opioid receptor.2 Two identical phase 3 studies (KODIAC-04 and KODIAC-05) examined the rate of spontaneous bowel movements (SBMs) in outpatients with noncancer pain and OIC (n=652 and 700 respectively) who were randomly assigned to receive 12.5mg or 25mg of naloxegol or placebo daily. The primary endpoint was the number of SBMs over a 12-week period.2

Response rates were significantly higher with 25mg of naloxegol than with placebo in study 04 and study 05 (44.4% vs. 29.4%, [P=0.001] and 39.7% vs. 29.3%, [P=0.02] respectively). In patients with initially inadequate response to laxatives, response rates to naloxegol in studies 04 and 05 were 48.7% vs. 28.8%, (P=0.002) and 46.8% vs. 31.4%, (P=0.01) respectively. In study 04, response rates were also higher in the group treated with 12.5mg of naloxegol. Adverse events, which included diarrhea and abdominal pain, occurred most frequently in the group receiving 25mg.2

“It is not surprising that some patients receiving naloxegol got diarrhea, since they are relieving constipation,” Dr. Chey observes. “And by inhibiting the effects of opioids in the GI tract, patients may start experiencing abdominal pain they had not felt previously.”

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Naloxegol is FDA-approved for treatment of OIC in adult patients with chronic non-malignant pain.15