FDA Expands Relistor's Indication
Treating opioid-induced constipation (OIC) just got easier. The Food and Drug Administration has expanded the indication for methylnaltrexone bromide (Relistor) to include OIC in patients with chronic noncancer pain.1
Previously, the drug was approved in 2008 for the treatment of OIC in patients with advanced disease requiring palliative care.
How it Works
According to Salix Pharmaceuticals, Relistor is a peripherally acting mu opioid receptor antagonist.The agent works by blocking the constipating effects of opioids in the gastrointestinal tract (local mu receptors), without adversely interfering with the analgesic effects of the opioid.
How it Was Approved
The FDA initially asked Salix to provide additional information to complete its application. The agency based its approval on the results of a randomized, double-blind, placebo-controlled trial including a total of 312 patients with a history of noncancer pain who were taking opioids for at least 1 month prior to study entry. All had confirmed constipation, defined as <3 spontaneous bowel movements per week.
According to Salix, the median duration of constipation at baseline was 59 months. The median daily baseline oral morphine equivalent dose was 161 mg. Patients were randomized to receive a subcutaneous injection of methylnaltrexone 12 mg or placebo once daily for 4 weeks, followed by an 8-week open-label phase where patients could take medications as needed.
The results of the study found a significantly great proportion of patients taking methylnaltrexone reported having 3 or more spontaneous bowel movements during the 4-week double-blind period vs placebo (59% vs 38%). After the first dose, 33% of treated patients reported having a spontaneous bowel movement within 4 hours, and approximately 50% had a bowel movement prior to the second dose.
According to the company, treatment was well tolerated, and adverse events were consistent with those seen with other studies of the drug in an advanced illness population. The most common side effects were abdominal pain (21%), diarrhea (6%), nausea (9%), and hyperhidrosis (6%). Relistor is contraindicated in patients with known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation.
Last month, the FDA approved naloxegol (Movantik) for the treatment of OIC in adults with chronic noncancer pain. First approved in 2006, Amitiza (lubiprostone) was approved last year for opioid-induced constipation. Amitiza is not recommended for patients taking methadone. According to the product information, Amitiza is a locally acting chloride channel activator. By increasing intestinal fluid secretion, the agent increases motility in the intestine, thereby relieving constipation.