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.