WebMD Health News
Daniel J. DeNoon
Louise Chang, MD
May 28, 2008 -- Results only now reported from a 12-week clinical trial that
ended nine years ago suggest that a new drug, Resolor, helps people with
Meanwhile, promising findings suggest that a new form of naltrexone, a drug
used to block the narcotic effects of opioids in addicts, may relieve the terrible
constipation that afflicts patients who need opioids to control their pain.
The Resolor results appeared only after Johnson & Johnson, which
developed the drug, licensed it to the Belgian firm Movetis NV.
Late or not, the results may be good news to the estimated 15% of Americans
who suffer the straining, bloating, and abdominal discomfort of chronic
Resolor "significantly increased the number of spontaneous, complete
bowel movements, reduced the severity of symptoms, and improved the disease-related quality of
life in patients with severe chronic constipation," report Mayo Clinic
researcher Michael Camilleri, MD, and his Movetis colleagues.
Nearly half of the patients receiving Resolor, but only a fourth of the
patients receiving an inactive placebo, averaged at least one complete bowel
movement per week.
None of the patients showed signs of heart problems. That's good news, but
there's reason to need more safety data, says Arthur J. Moss, MD, of the
University of Rochester in New York. Moss' editorial accompanies the Camilleri
report in the May 29 issue of The New England Journal of Medicine.
Resolor is in the same drug family as Propulsid and Zelnorm, both of which
were taken off the market because they caused dangerous heart problems in some
patients. Zelnorm returned to the market with a dire warning on its label, but
was then voluntarily removed from the market by the manufacturer.
"It is not clear why clinical trials with [Resolor] were temporarily
suspended around 2001 or why it took so long to bring this study to
publication," Moss notes. "We simply do not know whether the drug will
[cause serious heart problems] in a small fraction of vulnerable subjects with
a non-life-threatening gastrointestinal disorder."
Moss says more complete data will be needed before the drug should be
brought to market as a treatment for chronic constipation.
Opioid drugs are a huge boon in
offering pain relief to patients with severe pain. But they cause their own
form of suffering -- constipation that often cannot be relieved by laxatives.
This problem often means patients have to cut back on opioid use, sometimes
with a terrible increase in pain.
The drug naltrexone blocks opioid
drugs from attaching to receptors, thus blocking their painkilling effects.
Relistor is a form of naltrexone that has limited ability to enter the brain.
The idea is to block the unwanted side effects of opioids, such as
constipation, without blocking their painkilling effects.
In a clinical trial supported by Progenics, which is developing Relistor in
collaboration with Wyeth, 133 patients with advanced illness and terminal
disease who had been on opioids for two or more weeks received under-the-skin
injections of Relistor or an inactive placebo.
Nearly half the Relistor-treated patients had a bowel movement within four
hours of the first dose, compared with 15% of the placebo group. Time to bowel
movement was significantly shorter for Relistor patients than placebo
Importantly, none of the patients showed signs of opioid withdrawal or had
changes in their pain scores.
Relistor "may represent an important therapeutic option for patients
with advanced illness who are suffering from opioid-induced constipation,"
conclude Jay Thomas, MD, PhD, of San Diego Hospice and the Institute for
Palliative Medicine, San Diego, and colleagues.
In an editorial accompanying the Thomas report in the May 29 issue of The
New England Journal of Medicine, Harvard researchers Charles Berde, MD,
PhD, and Samuel Nurko, MD, MPH, commend the Thomas team on its work.
However, Berde and Nurko wonder why only half of patients responded. Their
hypothesis is that the constipating effects of opioids stem not only from
opioid action in the gut, but also in the brain, which Relistor cannot
"Future studies in a larger number of patients may help to delineate
predictors of the success or failure of [Relistor] in specific subgroups of
patients, and may guide decisions about increasing or decreasing the dose for
various patients," they suggest.
Relistor was approved by the FDA in April 2008 for the treatment of
opioid-induced constipation in patients with late-stage, advanced illness who
are receiving opioids on a continuous basis to help alleviate their pain.
SOURCES:Camilleri, M. The New England Journal of Medicine, May 29, 2008; vol
358: pp 2344-2354.Moss, A.J. The New England Journal of Medicine, May 29, 2008; vol
358: pp 2402-2403.Thomas, J. The New England Journal of Medicine, May 29, 2008; vol
358: pp 2332-2343.Berde, C. and Nurko, S. The New England Journal of Medicine, May 29,
2008; vol 358: pp 2400-2402.
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