Did opioid-induced constipation contribute to Elvis Presley’s death? Would he still be making music today if he’d won the battle with his bowels? Though many disagree, Elvis’ former personal physician thinks that a cure for the King’s constipation might have spared his life.
If this kind of conjecture from suspicious minds leaves you all shook up (or at least wishing for a little less conversation), simply consider this: Opioid-induced constipation adversely affects quality of life for millions of Americans annually. Many of these individuals obtain little relief from lifestyle changes and laxatives. Peripherally acting m-opioid receptor antagonists mitigate the effect of opioids on the gastrointestinal tract, yet neither of the currently available agents are approved by the FDA for use in outpatients with chronic noncancer pain. Are there any other options on the horizon?
In this week’s NEJM, Dr. William D. Chey (University of Michigan Health System, Ann Arbor, MI) and his KODIAC colleagues present two identically-designed multicenter randomized phase III trials of a new peripherally acting m-opioid receptor antagonist. The two trials randomized a total of 1352 adult outpatients with noncancer pain and opioid-induced constipation to one of three groups: Higher-dose naloxegol (25mg daily), lower-dose naloxegol (12.5mg daily), or placebo. Laxative and other bowel regimens were stopped, and patients recorded bowel movements and pain levels in a daily diary for the duration of the trial.
After 12 weeks of treatment, patients in the higher-dose naloxegol groups were more likely to respond than were placebo-treated patients (40% vs 29% and 44% vs 29%; p<0.025 for both). Adverse events such as abdominal pain and diarrhea were significantly more common in the higher-dose naloxegol groups than among the placebo groups (61% vs 47% and 69% vs 59%; p<0.01 for both). Lower-dose naloxegol was superior to placebo in only one of the two trials. Serious adverse events, pain scores, and daily opioid doses were similar across all groups.
“Constipation is a major concern for many patients taking opioids,” says primary-care provider and NEJM Deputy Editor Dr. Mary Beth Hamel. “These studies did not compare naloxegol to other available treatments for constipation, and the observed benefits over placebo were not large. Nevertheless, peripheral m-opioid receptor antagonists may be one more option for patients and clinicians to try.”