Naloxegol, a new drug for the treatment of opioid-induced constipation

Abstract

Introduction: With increasing chronic opioid use, opioid-induced constipation (OIC) is becoming a relevant clinical challenge. Presently, only few treatments have been demonstrated to be more effective than placebo in treating OIC but most of them have a restricted clinical application because of side effects. Naloxegol, an orally administered, peripherally acting, μ-opioid receptor antagonist (PAMORA), was developed for the treatment of OIC.

Area covered: This review summarizes published information and presentations at meetings on the effects of naloxegol in OIC. Pharmacodynamic studies have demonstrated that naloxegol inhibits gastrointestinal opioid effects while preserving central analgesic actions. Phase II and Phase III studies in patients with non-cancer OIC have confirmed the efficacy of naloxegol to inhibit OIC, and the most consistent efficacy was seen with the 25 mg dose once daily. Adverse events were mainly gastrointestinal in origin and usually transient and mild. There were no signs of opioid withdrawal in the studies. Safety and tolerability were also shown in a long-term safety study. Regulatory authorities have recently approved the use of naloxegol in OIC.

Expert opinion: Naloxegol is the first approved, orally available PAMORA. The drug has the potential to substantially improve management of OIC patients.

Keywords:

• naloxegol
• opioid-induced constipation
• opioid withdrawal
• randomized controlled clinical trial

Declaration of interest

This paper was supported by a Methusalem grant from Leuven University to J Tack. Leuven University has received financial compensations for advice of J Tack to AstraZeneca on opioid-induced constipation and naloxegol clinical studies. J Tack has also received honoraria from Astrazeneca, Shire and Sucampo. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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