Which medication is used in the treatment of opioid-induced constipation (OIC) in adults with chronic noncancer pain and how effective is it?

Updated: Jul 05, 2019
  • Author: Marc D Basson, MD, PhD, MBA, FACS; Chief Editor: BS Anand, MD  more...
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Answer

Naloxegol (Movantik) is a peripherally-acting mu-opioid receptor antagonist (PAMORA) that was approved by the FDA in September 2014 for OIC in adults with chronic noncancer pain. [49, 50] Approval was based on two randomized, multicenter, placebo-controlled, 12-week studies involving 1352 adult patients.

In the first study, 44% of patients treated with 25 mg of naloxegol and 41% of those treated with 12.5 mg of naloxegol had an increase in the number of bowel movements per week, compared with 29% of patients who received placebo. [49] Results were similar in the second study. Common adverse effects included abdominal pain, diarrhea, headache, and excessive gas. The FDA is requiring a postmarketing study to further examine the potential risk for cardiovascular adverse events with naloxegol treatment.

Data from the KODIAC clinical trial program regarding naloxegol consisted of 4 studies: KODIAC-4, -5, -7, and -8. [51, 52] KODIAC-4 and -5 were placebo controlled, double-blind, 12-week studies assessing safety and efficacy, [51] whereas KODIAC-7 was a 12-week safety extension to KODIAC-4, and KODIAC-8 was a 52-week open-label, long-term safety study. [52]

Methylnaltrexone (Relistor) is a PAMORA indicated for opioid-induced constipation in adults with chronic noncancer pain. [53] It is also indicated for adults with advanced illness who are receiving palliative care when response to laxative therapy has been insufficient. In a randomized, double blind, placebo-controlled trial, patients (n = 312) with chronic noncancer pain were given methylnaltrexone 12 mg SC once daily. A significantly greater portion of patients taking daily methylnaltrexone reported having 3 or more spontaneous bowel movements per week during the 4-week double-blind period compared to those taking placebo (59% vs 38%). Following the first dose, 33% of patients in the treatment group had a spontaneous bowel movement within 4 hours, and approximately half of patients had a spontaneous bowel movement prior to the second dose. [53]

Naldemedine (Symproic), another PAMORA, was approved by the FDA in March 2017 for opioid-induced constipation in adults with noncancer pain. [54]  Approval was based on the COMPOSE clinical trials. COMPOSE III was a 52-week, randomized, double-blind, placebo-controlled, long-term safety study that included approximately 620 adults with opioid-induced constipation and chronic noncancer pain. The treatment group showed significant improvements in weekly bowel movement frequency compared with placebo at all time points measured (P ≤0.0001), and no significant opioid withdrawal signs or symptoms were noted. [54, 55]


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