Naloxegol: First oral peripherally acting mu opioid receptor antagonists for opioid-induced constipation

Abstract

Opioid-induced constipation (OIC) is one of the most troublesome and the most common effects of opioid use leading to deterioration in quality of life of the patients and also has potentially deleterious repercussions on adherence and compliance to opioid therapy. With the current guidelines advocating liberal use of opioids by physicians even for non-cancer chronic pain, the situation is further complicated as these individuals are not undergoing palliative care and hence there cannot be any justification to subject these patients to the severe constipation brought on by opioid therapy which is no less debilitating than the chronic pain. The aim in these patients is to prevent the opioid-induced constipation but at the same time allow the analgesic activity of opioids. Many drugs have been used with limited success but the most specific among them were the peripherally acting mu opioid receptor antagonists (PAMORA). Methylnaltrexone and alvimopan were the early drugs in this group but were not approved for oral use in OIC. However naloxegol, the latest PAMORA has been very recently approved as the first oral drug for OIC. This article gives an overview of OIC, its current management and more specifically the development and approval of naloxegol, including pharmacokinetics, details of various clinical trials, adverse effects and its current status for the management of OIC.

2017 update on pain management in patients with chronic kidney disease

“…Naloxegol is metabolized via CYP3A4 and is a P-glycoprotein substrate. As such, it has a similar drug–drug interaction profile as the calcineurin inhibitors [ 62 , 63 ].…”

Opioid-induced bowel dysfunction: suggestions from a multidisciplinary expert Board

“…Because the predominant actions of opioids on the gastrointestinal tract are mediated by mu receptors, the administration of specific peripherally acting mu-opioid receptor antagonists (PAMORAs) is advisable. Methylnaltrexone and alvimopan were the early drugs in this group but they were not approved for oral use in OIBD [3, 26]. Naloxegol (Moventig®, Kyowa Kirin), the latest PAMORA, has been recently approved as the first oral drug for OIBD [27].…”

The Basic Pharmacology of Opioids Informs the Opioid Discourse about Misuse and Abuse: A Review

“…While laxatives and other conventional constipation treatments may be employed, OIC may be laxative-refractory [ 107 ]. Peripherally acting MOR antagonist (PAMORA) agents, such as naloxegol and methylnaltrexone, may be helpful [ 108 – 111 ]. Combination drugs that incorporate an opioid + naltrexone may also be useful; a timed-release mechanism allows the antagonist (e.g., naltrexone) to be active as the drug passes through the GI system, but the antagonist is metabolized before the agonist enters the systemic circulation [ 112 ].…”