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Peripheral Opioid Antagonist for Opioid-Induced Constipation

Within 4 hours of the first dose, defecation occurred in 48% of methylnaltrexone patients and in 15% of the placebo patients.

Constipation is common among people who take opioids chronically. In a randomized manufacturer-sponsored study, the peripheral opioid antagonist methylnaltrexone was investigated as therapy for opioid-induced constipation among 133 terminally ill patients who were treated at nursing homes, hospices, or palliative-care centers. All patients were taking opioids (median morphine equivalent doses, 100–150 mg) and had fewer than three bowel movements per week; they received every-other-day injections of methylnaltrexone or placebo.

Within 4 hours of the first dose, defecation occurred in 48% of methylnaltrexone patients and in 15% of the placebo patients. Similarly, after two or more of the first four study-drug doses, defecation within 4 hours occurred more often among methylnaltrexone patients than placebo patients (52% vs. 8%). The response to methylnaltrexone appeared consistent throughout a 3-month open-label extension period. Abdominal pain, flatulence, and nausea were 4% to 6% more common with methylnaltrexone, but pain and opioid withdrawal symptoms were similar between groups.

Comment: Editorialists, who praised the investigators for conducting a challenging real-world study, noted that the medication was not effective about half of the time, probably because of the many causes and contributors to constipation among terminally ill patients on chronic opioids. In fact, one might speculate that the medication would have even greater efficacy in patients with less comorbidity, such as patients who take chronic opioids to treat addiction. Methylnaltrexone is not yet available, but such drugs — which use a specific, targeted therapy such as a peripheral opioid antagonist — hold promise for treatment of one of the most common and troublesome side effects of chronic opioid use.

— Richard Saitz, MD, MPH, FACP, FASAM

Published in Journal Watch General Medicine May 28, 2008

Citation(s):

Thomas J et al. Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med 2008 May 29; 358:2332.

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Berde C and Nurko S. Opioid side effects — Mechanism-based therapy. N Engl J Med 2008 May 29; 358:2400.

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• Medline abstract (Free)