Comparison of Diarrhea Incidence Following Initial Naldemedine Administration in Patients Receiving Strong Opioids: A Retrospective Cohort Study

Naldemedine is commonly prescribed for opioid-induced constipation but can cause diarrhea. Diarrhea incidence following naldemedine initiation may vary across background opioids. We conducted a single-center retrospective cohort study of hospitalized adults with cancer who initiated naldemedine while receiving strong opioids between November 2021 and December 2024 to quantify diarrhea incidence within 7 days of naldemedine initiation by opioid type (graded according to the Common Terminology Criteria for Adverse Events version 5.0) and explore the associated factors. Covariates included demographics, Eastern Cooperative Oncology Group performance status, oral morphine equivalents, and selected concomitant medications and clinical factors. Univariate logistic regression was used to explore associations with diarrhea. Thirty-nine patients were included (morphine, 1; oxycodone, 27; fentanyl, 5; hydromorphone, 6). Overall, 33% (13/39) developed diarrhea, all of which were mild (grades 1-2). Diarrhea incidence varied by opioid type: morphine (0%, 0/1), oxycodone (26%, 7/27), fentanyl (80%, 4/5), and hydromorphone (33%, 2/6). Exploratory analyses suggested that fentanyl use and female sex were associated with diarrhea incidence, although estimates were imprecise. Early post-naldemedine diarrhea incidence was common but uniformly mild, with a higher incidence among fentanyl recipients, but these hypothesis-generating findings require validation in larger prospective studies.