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Clinical Q & A with Joseph Pergolizzi, MD
Q: Are there any effective strategies for managing opioid-induced bowel dysfunction (OBD)?
Opioid-induced bowel dysfunction (OBD), usually associated with severe, persistent constipation, is one of the most common and debilitating side-effects of opioid therapy for chronic pain. While it is understood that the primary cause of OBD is the activation of mu-opioid receptors in the intestine by opioid pain medications, there are currently no approved treatments that specifically address this mechanism. Therefore, therapy for OBD is dependent on opioid-sparing strategies, which may compromise adequate pain control, and the use of a variety of over-the-counter or prescription laxative agents.
Several types of laxatives are available, including bulk-forming agents (and increased fiber intake), osmotic agents (that draw more fluid into the gut to liquefy the stool), and nonspecific stimulants. Physicians often recommend one of these agents with new prescriptions for an opioid pain reliever. However, in order to get adequate efficacy, experimenting with dosing or additional laxatives is often necessary. One study suggested that only about half the people taking opioids got the same relief from laxatives as people who were not taking opioids.1 While laxatives may provide limited relief from OBD, their effects are often unpredictable, and they can be associated with side effects, such as abdominal cramping, bloating, and diarrhea. As a result, they are not recommended for long-term use.
The approval of methylnatrexone bromide (Relistor®) marks the first US Food and Drug Administration (FDA) approval of a new class of agents called peripherally-acting mu-opioid receptor (PAM-OR) antagonists. As their name suggests, these agents specifically block the “peripheral” action of opioids on the gut without interfering with pain relief mediated in the central nervous system. Relistor® is indicated to help restore bowel function in patients with late-stage, advanced illness who are receiving opioids on a continuous basis to help alleviate their pain.
Alvimopan, another PAM-OR antagonist, is the first and only FDA-approved agent indicated to accelerate the time to upper and lower gastrointestinal recovery following partial large or small bowel resection surgery with primary anastomosis. This agent is currently under development for OBD. In several large OBD clinical trials, alvimopan, has already been shown to increase bowel movement frequency. PAM-OR antagonists, such as Relistor® and possibly alvimopan can provide an effective and well-tolerated tool for managing OBD.
Finally, NKTR-118 is an investigational oral drug that combines a novel small molecule PEGylation technology platform with naloxol, a derivative of the opioid-antagonist drug, naloxone. In preclinical studies, NKTR-118 did not cross the blood-brain barrier, an important potential advance for this therapy, which could allow it to act selectively in a similar fashion as PAM-OR antagonists.
Joseph Pergolizzi, MD, is an Adjunct Assistant Professor at Johns Hopkins University School of Medicine in Baltimore, Maryland.
Reference
1. Pappagallo M. Incidence, prevalence, and management of opioid bowel dysfunction. Am J Surg. 2001;182(5A Suppl):11S-18S.
RSDSA Review. 2006;19(4):8.
Updated October 28, 2008 |
