Naloxegol Alleviates Opioid-Induced Constipation

Authors: Chey WD et al., N Engl J Med 2014 Jun 19; 370:2387

About eight patients had to be treated to benefit one.

Binding of opioid drugs to intestinal μ-opioid receptors causes the troublesome side effect of constipation. In two identical randomized trials, industry-sponsored researchers have examined the efficacy of naloxegol (Movantik) — a μ-opioid–receptor antagonist currently under FDA review — for treating patients with opioid-induced constipation. The drug does not cross the blood-brain barrier and, thus, does not interfere with opioid analgesia.

A total of 1352 outpatients who were receiving long-term opioid therapy for noncancer pain were enrolled in the two studies; all patients had <3 spontaneous bowel movements weekly plus hard stools, straining, or sensation of incomplete evacuation. Patients received daily placebo or naloxegol (12.5 mg or 25 mg). At 12 weeks, the primary endpoint (greater than 3 bowel movements weekly) occurred significantly more often in 25-mg naloxegol recipients than in placebo recipients (42% vs. 29%; number needed to treat, ≈8); recipients of 12.5 mg had outcomes intermediate between those of the 25-mg and placebo groups. A dose-response effect also was noted for improvement in straining and stool consistency. The most common side effects of naloxegol were abdominal pain and diarrhea.

Comment

Naloxegol was more effective than placebo for alleviating opioid-induced constipation, but eight patients had to be treated with 25 mg to benefit one patient. Two μ-opioid–receptor antagonists are currently FDA-approved for bowel indications: methylnaltrexone (Relistor; for opioid-induced constipation in patients with advanced illnesses who are receiving palliative care) and alvimopan (Entereg; to hasten recovery of bowel function after partial bowel resection with primary anastomosis).