Takagi Y, et al. - Researchers conducted this multicenter retrospective cohort study to extensively identify risk factors and appropriate management strategies for key adverse events including diarrhea associated with naldemedine, a novel peripherally-acting mu-opioid receptor antagonist (PAMORA), among patients receiving opioids. Eligible patients had cancer, had received palliative care at participating centers, had daily opioids administered and taken at least one dose of naldemedine between June 2017 and March 2018. Of the 103 patients receiving naldemedine, 98 [median age was 68 years] had met the eligibility criteria. Findings suggested that early administration of naldemedine after initiation of opioids may significantly decrease adverse events including diarrhea. Diarrhea caused by naldemedine should be managed by avoiding other laxatives while the naldemedine continues. Taking into account the mechanism of adverse events of naldemedine and other PAMORA, new approaches indicated in this study for the safer management of opioid-induced constipation may potentially be extrapolated to other PAMORA.