PAMORAs help achieve response in opioid-induced constipation
Peripherally acting mu-opioid receptor antagonists helped patients with opioid-induced constipation achieve therapeutic response, according to a meta-analysis published in Alimentary Pharmacology & Therapeutics.
Michael Camilleri, MD, from Mayo Clinic in Rochester, Minnesota, and colleagues wrote that opioid-induced constipation can decrease treatment satisfaction and can lead patients to discontinue opioid therapy.
“Mu-opioid receptors are expressed on enteric nerve cell bodies and facilitate potassium channel activation, membrane hyperpolarization and inhibition of ongoing neural activity and transmitter release resulting in inhibition of motility and fluid secretion, including retardation of colonic transit,” they wrote. “The aim of this systematic review and meta-analysis was to evaluate multiple efficacy endpoints that address all aspects of bowel function and individual adverse effects of [peripherally acting mu-opioid receptor antagonists (PAMORAs)], mu-opioid antagonists and agents targeting chronic constipation in patients with opioid-induced constipation.”
Investigators searched the literature for controlled trials compared with placebo. They evaluated FDA approved doses or highest studied dose and based efficacy on several endpoints, including bowel function index and Bristol Stool Form scale, as well as responder analysis (a combination of >3 spontaneous bowel movements or complete spontaneous movements plus 1 spontaneous bowel movement or complete spontaneous bowel movements, respectively, over baseline). They also assessed for adverse events.
In 35 trials, comprising 13,566 patients, that fit the study criteria, all PAMORAs demonstrated efficacy on diverse patient response endpoints. Approved doses of methylnaltrexone, naloxegol and naldemidine had greater efficacy, while a combination of oxycodone with naloxone, lubiprostone and linaclotide had lower efficacy or lower efficacy with higher adverse events.
“This systematic review and meta-analysis has shown that therapeutic response in opioid-induced constipation is best achieved with the PAMORAs, methylnaltrexone, naloxegol and naldemidine, with low risk of serious adverse events or opioid withdrawal,” Camilleri and colleagues wrote. – by Alex Young
Disclosures: Camilleri reports serving as a consultant or author with no personal compensation to AstraZeneca and Shionogi. He also reports financial ties to AEON Biopharma, Alfasigma, Allergan, CME Outfitters, Dignify Therapeutics, Enterin, Ironwood, Kallyope and Takeda. Please see the full study for all other authors relevant financial disclosures.