Naldemedine may improve opioid-induced constipation

Last Updated: 2018-02-28

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Naldemedine, a mu-opioid receptor antagonist, can relieve opioid-induced constipation in patients with chronic non-cancer pain, new industry-sponsored research suggests.

"Long-term naldemedine treatment elicited significant and durable improvements in the frequency of bowel movements, constipation-related symptoms, and patient quality of life," Dr. Tadaaki Yamada of Florham Park, New Jersey-based Shionogi Inc. and colleagues write in Pain, online February 6.

For the study, a double-blind phase 3 trial called COMPOSE-3, 1,246 participants from 195 international sites were randomly assigned to receive either once-daily oral naldemedine 0.2 mg or placebo for 52 weeks. All participants had been taking a stable daily dose of opioids (30 mg or more oral morphine-equivalents) for at least one month at enrollment and had opioid-induced constipation.

Compared with placebo, the naldemedine group showed significant sustained improvements in bowel movement frequency, constipation-related symptoms, and quality of life at all time points measured. Naldemedine was well tolerated and did not interfere with opioid-mediated pain relief or precipitate opioid withdrawal.

Treatment-emergent adverse events and treatment-emergent adverse events causing study discontinuation occurred with similar frequencies overall in the active and placebo groups (68.4% vs. 72.1%, respectively; and 6.3% vs. 5.8%, respectively).

Diarrhea was reported significantly more frequently with naldemedine (11.0%) than with placebo (5.3%). The researchers found "no meaningful differences" between the groups in pain intensity or opioid withdrawal.

Dr. Kimberly M. Mauer, associate professor of anesthesiology and perioperative medicine at the Oregon Health & Science University School of Medicine in Portland, told Reuters Health by email, "As providers prescribe less opioids and patients consume less opioids, opioid-induced constipation is something we are seeing less and less of."

"In general, at least in our practice here and in my experience at my other institution for pain training and where I was an attending, over-the-counter medications for constipation work just as well as these newly invented and mu-opioid-receptor-antagonist medications," said Dr. Mauer, who was not involved in the study.

"In addition," she noted, "the mu-opioid-receptor-antagonist anti-constipation medications have the potential to remove some of the analgesia effect of the opioids, which is undesirable."

"Moreover," Dr. Mauer explained, "we are moving away from pharmaceuticals in general for opioid-induced constipation. Most of our patients are using home-made fruit paste, senna teas and diet control to combat opioid constipation instead of relying on pharmaceutical options. Essential oils and naturopathic remedies are also gaining in popularity."

Neither Shionogi nor the study's corresponding author responded to requests for comment by press time.

Shionogi Inc., which makes naldemedine, funded and sponsored the study. All of the authors are employees of or have other financial relationships with Shionogi. Several others also have financial relationships with other pharmaceutical companies.

SOURCE: http://bit.ly/2CClHNW

Pain 2018.