An oral formulation of methylnaltrexone bromide (Relistor) has received US Food and Drug Administration (FDA) approval for the treatment of opioid-induced constipation (OIC) in adults with chronic noncancer pain, Valeant Pharmaceuticals International Inc and Progenics Pharmaceuticals Inc have announced.
In 2008, the FDA approved methylnaltrexone subcutaneous injections (12 mg and 8 mg) for the treatment of OIC in adults with advanced illness receiving palliative care. In 2014, the agency approved that treatment in adults with chronic noncancer pain.
Now, an oral formulation has been approved for OIC in noncancer pain. Valeant projects that sales of the tablets will begin in the United States during the third quarter of 2016, notes a statement released July 19.
Approval comes after positive results from a randomized, double-blind, phase 3 trial that compared once-daily dosing of 450-mg methylnaltrexone tablets (n = 200) with placebo (n = 201) in adults with chronic noncancer pain.
In the treatment group, there were statistically significant improvements in rescue-free bowel movement (RFBM) within 4 hours of administration over 28 days of dosing compared with placebo treatment, achieving the primary endpoint.
The treatment group also had a higher percentage of responders (those with 3 or more RFBMs/week, with an increase of 1 or more from baseline for at least 3 of the 4 weeks) than the placebo group.
Overall, the efficacy of the treatment was similar to that reported in clinical studies of subcutaneous methylnaltrexone in patients with chronic noncancer pain.
The study showed that the overall safety profile in treated patients was also similar to that in patients taking placebo.
The most common adverse reactions (occurring in at least 12%)in patients with chronic noncancer pain who had OIC and received oral methylnaltrexone include abdominal pain, diarrhea, headaches, anxiety, muscle spasms, and chills. Adverse reactions of abdominal pain, diarrhea, hyperhidrosis, anxiety, rhinorrhea, and chills may reflect symptoms of opioid withdrawal.
Treatment is contraindicated in patients with known or suspected gastrointestinal obstruction and those at increased risk for recurrent obstruction because of the potential for gastrointestinal perforation, the company said.
If severe or persistent diarrhea occurs during treatment, patients should discontinue therapy and consult their healthcare provider, the statement notes.
Patients should avoid concomitant use with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk for opioid withdrawal.
The product has a unique mechanism of action in that it binds to mu-opioid receptors without affecting the opioid-mediated analgesic effects on the central nervous system, said Richard L. Rauck, MD, medical director of the Center for Clinical Research, president of the , Carolinas Pain Institute, and immediate past president of the World Institute of Pain, said in the statement.
"This represents a true breakthrough in the treatment of OIC and addresses a large and growing need in the field of pain management," he said.
"Opioid-induced constipation represents a long-lasting and potentially debilitating side effect of opioid therapy for millions of patients suffering from chronic pain," commented Joseph C. Papa, chief executive officer of Valeant, in a press release. "We believe oral Relistor represents a new alternative treatment for OIC, and we look forward to introducing the more convenient oral formulation as soon as practicable."
"We are delighted that this milestone for Relistor has been achieved and that patients suffering from OIC will have this new treatment option," commented Mark Baker, chief executive officer of Progenics, in the press release. "We expect the market to be receptive to a more convenient oral tablet formulation of Relistor's well-established subcutaneous preparation."