FDA Approves Oral Relistor for Opioid-Induced Constipation in Adults With Noncancer Pain

Significant improvement observed within four hours of administration

The FDA has cleared Relistor (methylnaltrexone bromide, Valeant Pharmaceuticals/Progenics Pharmaceuticals) tablets for the treatment of opioid-induced constipation (OIC) in adults with chronic noncancer pain. Sales of the product are expected to begin in the third quarter of 2016.

Relistor subcutaneous injection (12 mg and 8 mg) was approved in 2008 for the treatment of OIC in adults with advanced illness who are receiving palliative care, and in 2014 for the treatment of OIC in adults with chronic noncancer pain.

Methylnaltrexone is a selective antagonist of opioid binding at the mu-opioid receptor. As a quaternary amine, the ability of methylnaltrexone to cross the blood–brain barrier is restricted. This allows methylnaltrexone to function as a peripherally acting mu-opioid receptor antagonist in tissues such as the gastrointestinal (GI) tract, thereby decreasing the constipating effects of opioids without affecting opioid-mediated analgesic effects on the central nervous system.

A phase 3, randomized, double-blind trial was conducted to compare methylnaltrexone tablets (450 mg once daily; n = 200) with placebo tablets (n = 201) in adults with chronic noncancer pain. Methylnaltrexone tablets demonstrated statistically significant improvements in rescue-free bowel movement within four hours of administration during 28 days of dosing compared with placebo (the trial’s primary efficacy endpoint). The active-treatment group also achieved statistical significance for a key secondary efficacy endpoint, in which a higher percentage of responders was observed with methylnaltrexone treatment compared with placebo. Overall, the efficacy of oral methylnaltrexone in this study was comparable with that reported in clinical trials of subcutaneous methylnaltrexone in subjects with chronic noncancer pain.

Relistor tablets are contraindicated in patients with known or suspected GI obstruction and in patients at increased risk of recurrent obstruction because of the potential for GI perforation.

The most common adverse events observed in adult patients with OIC and chronic noncancer pain receiving Relistor tablets included abdominal pain, diarrhea, headaches, abdominal distention, hyperhidrosis, anxiety, muscle spasms, rhinorrhea, and chills. Abdominal pain, diarrhea, hyperhidrosis, anxiety, rhinorrhea, and chills may reflect symptoms of opioid withdrawal.

Sources: Valeant Pharmaceuticals; July 19, 2016; and Relistor Prescribing Information; September 2015.