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Spotlight on naldemedine in the treatment of opioid-induced constipation in adult patients with chronic noncancer pain: design, development, and place in therapy

Authors Stern EK, Brenner DM

Received 26 September 2017

Accepted for publication 23 December 2017

Published 15 January 2018 Volume 2018:11 Pages 195—199


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr E Alfonso Romero-Sandoval

Emily K Stern, Darren M Brenner

Division of Gastroenterology, Department of Internal Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Abstract: Opioid-induced constipation (OIC) is an increasingly prevalent problem in the USA due to the growing use of opioids. A novel class of therapeutics, the peripherally acting μ-opioid receptor antagonists (PAMORAs), has been developed to mitigate the deleterious effects of opioids in the gastrointestinal tract while maintaining central analgesia and minimizing opioid withdrawal. This review aimed to summarize the literature on naldemedine, the third PAMORA to gain US Food and Drug Administration (FDA) approval for the treatment of OIC in adults with chronic noncancer pain-related syndromes. Naldemedine has a chemical structure similar to naltrexone, an opioid receptor antagonist, with chemical modifications that limit its ability to cross the blood–brain barrier. Naldemedine was evaluated in two Phase II and three Phase III clinical trials prior to gaining FDA approval. In two pivotal identical Phase III trials, COMPOSE-I (NCT 01965158) and COMPOSE-II (NCT 01993940), patients receiving naldemedine were significantly more likely to respond when compared with placebo (COMPOSE-I: 47.6 vs 34.6%, P=0.002 and COMPOSE-II: 52.5 vs 33.6%, P<0.0001). The most frequent adverse events were abdominal pain (8%) and diarrhea (7%) – rates similar to the other PAMORAs. Based on the available data, naldemedine appears to be an effective and safe drug for the treatment of OIC in adults with chronic noncancer pain.

Keywords: opioid-induced constipation, constipation, opioids, opioid antagonist, naldemedine, peripherally acting u-opioid receptor antagonists, PAMORA

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