A Different Kind of Constipation Needs a Different Kind of Treatment

RELISTOR targets the underlying cause of opioid-induced constipation

Watch this video about the pathophysiology and consequences of opioid-induced constipation. See how the targeted action of RELISTOR can block opioids from binding to peripheral mu-opioid receptors, inhibiting their constipating effects on the GI tract without compromising opioid-mediated analgesic effects on the central nervous system.1-3

Opioid-Induced Constipation (OIC) and RELISTOR Transcript

OIC: A Serious Consequence
The Science of OIC
Targeting the Source of OIC

OIC: A Serious Consequence

Despite proven analgesic efficacy, the use of opioids is commonly associated with constipation that is a barrier to effective pain management.

Opioid-induced constipation may be debilitating and can even cause patients to discontinue much needed pain relief.

Opioid-induced constipation can be a persistent problem because tolerance to the constipating effects of opioids rarely develops.

The opioid dose that produces constipation may be 4-fold less than the analgesic dose.

While laxatives treat the symptoms of opioid-induced constipation, they do not address its underlying cause and are often insufficient.

Understanding the science behind opioid-induced constipation reveals why it is important to have treatment options that target the actual cause of this common and troublesome effect of opioid therapy.

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The Science of OIC

Nearly all opioids are small molecules that can easily permeate the blood-brain barrier. Within the central nervous system, these molecules interact with mu-opioid receptors to exert an analgesic effect.

Opioid receptors can also be found in the periphery, such as the gastrointestinal tract.

While opioids are exerting their desirable analgesic effects centrally at the mu-opioid receptor, they are also causing undesirable adverse effects peripherally, including gastrointestinal function.

The goal should be to separate the undesirable peripheral effect of opioids on the gastrointestinal tract from the central analgesic effect.

In the gastrointestinal tract, the activation of mu-opioid receptors in the enteric nervous system can result in opioid-induced constipation.

It is multifactorial, arising from a combination of gastrointestinal effects such as reduced motility, increased reabsorption of fluid in the intestine, and decreased epithelial secretion.

Since opioid-induced constipation involves this decrease in intestinal motility, fiber intake in these patients could cause bowel obstruction and potential impaction.

And while laxatives may treat the symptoms of opioid-induced constipation, they lack direct effects on mu-opioid receptors, the principal mediators of opioid-induced constipation.

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Targeting the Source of OIC

RELISTOR is indicated for the treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Use of RELISTOR beyond four months has not been studied.

RELISTOR (methylnaltrexone bromide) is a peripherally acting selective antagonist of opioid binding at the mu-opioid receptor.

The unique molecular structure of RELISTOR restricts it from crossing the blood-brain barrier; therefore, it does not interfere with the desired action of opioids on the centrally located mu-opioid receptors.

RELISTOR is a competitive antagonist that occupies the mu-receptors in the GI tract.

This targeted action of RELISTOR blocks opioids from binding to inhibit their constipating effects on the GI tract.

Therefore, RELISTOR can effectively treat the constipation initiated by the peripheral action of opioids to mu-receptors in the GI tract without compromising opioid-mediated analgesic effects on the central nervous system.

By occupying the mu-receptor in the GI tract, RELISTOR can restore your patient's bowel function.

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The most common adverse events in clinical trials with RELISTOR were abdominal pain, flatulence, nausea, dizziness, diarrhea, and hyperhidrosis.

Indication for RELISTOR

RELISTOR® is indicated for the treatment of opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Use of RELISTOR beyond four months has not been studied.

Important Safety Information about RELISTOR

RELISTOR®  (methylnaltrexone bromide) Subcutaneous Injection is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

Cases of gastrointestinal (GI) perforation have been reported in adult patients with opioid-induced constipation and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the GI tract (i.e., cancer, peptic ulcer, Ogilvie's syndrome). Perforations have involved varying regions of the GI tract (e.g., stomach, duodenum, or colon). Use RELISTOR with caution in patients with known or suspected lesions of the GI tract. Advise patients to discontinue therapy with RELISTOR and promptly notify their physician if they develop severe, persistent, or worsening abdominal symptoms.

If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their physician.

Use of RELISTOR beyond four months has not been studied.

Safety and efficacy of RELISTOR have not been established in pediatric patients.

The most common adverse reactions reported with RELISTOR compared with placebo in clinical trials were abdominal pain (28.5%), flatulence (13.3%), nausea (11.5%), dizziness (7.3%), diarrhea (5.5%), and hyperhidrosis (6.7%).

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch/ or call 1-800-FDA-1088.

For product information, adverse event reports, and product complaint reports, please contact:

Salix Product Information Call Center
Phone: 1-800-508-0024
Fax: 1-510-595-8183
Email: salix@medcomsol.com

Please see complete Prescribing Information for RELISTOR.

References 1. RELISTOR® (methylnaltrexone bromide) Prescribing Information, Salix Pharmaceuticals, Inc. 2. Yuan CS, Foss JF. Gastric effects of methylnaltrexone on mu, kappa, and delta opioid agonists induced brainstem unitary responses. Neuropharmacology. 1999;38(3):425-432. 3. Yuan CS, Israel RJ. Methylnaltrexone: a peripherally acting opioid antagonist. In: Dean R, Bilsky EJ, Negus SS, eds. Opiate Receptors and Antagonists: From Bench to Clinic. New York, NY: Humana Press; 2009:175-200.