Use of naldemedine is associated with reduced incidence of hyperactive delirium in cancer patients with opioid-induced constipation: A nationwide retrospective cohort study in Japan

Pharmacotherapy. 2022 Mar;42(3):241-249. doi: 10.1002/phar.2658. Epub 2022 Jan 21.

Abstract

Background: Medical benefits of peripherally acting mu-opioid receptor antagonists other than improving opioid-induced constipation remain unclear. Our aim was to evaluate the association between the use of naldemedine and incidence of hyperactive delirium in cancer patients receiving chemotherapy and opioid therapy.

Methods: We conducted a propensity score-matched analysis using a nationwide inpatient database in Japan. Cancer patients receiving both inpatient chemotherapy and opioid therapy from June 1, 2017, to March 31, 2018, were included. Patients receiving naldemedine were matched to control patients by propensity score. Our primary outcome was the incidence of hyperactive delirium during hospitalization, and secondary outcomes were the length of hospital stay, hospital costs, in-hospital mortality, and incidence of ileus.

Results: Of 34,031 patients receiving inpatient chemotherapy and opioid therapy, 1905 (5.6%) were included in the naldemedine group. After one-to-four propensity score matching, 1904 patients were included in the naldemedine group and 7616 in the control group. Naldemedine users had significantly reduced incidence of hyperactive delirium compared with the control patients (19.4% vs 23.3%; risk difference, -3.9 [95% confidence interval, -5.9 to -1.9]; risk ratio, 0.83 [0.75-0.92]; p<0.001; subdistribution hazard ratio, 0.85 [0.75-0.97]; p = 0.015). The median length of hospital stay was significantly shorter in the naldemedine group compared with the control group (12 days [interquartile range, 6-23] vs 14 days [6-26]; p = 0.001). The median hospital costs were also significantly lower in the naldemedine group compared with the control group (US $6179 [3351-10,026] vs US $6576 [3436-11,107]; p < 0.001). No significant differences were found for in-hospital mortality or incidence of ileus between the groups.

Conclusions: Our findings suggest that the use of naldemedine may have benefits in preventing hyperactive delirium, shortening hospital stay, and decreasing hospital costs in cancer patients receiving chemotherapy and opioid therapy.

Keywords: delirium; naldemedine; observational study; opioid-induced constipation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / adverse effects
  • Constipation / chemically induced
  • Constipation / drug therapy
  • Constipation / epidemiology
  • Delirium* / chemically induced
  • Delirium* / epidemiology
  • Delirium* / prevention & control
  • Humans
  • Ileus* / chemically induced
  • Ileus* / drug therapy
  • Incidence
  • Japan / epidemiology
  • Naltrexone / analogs & derivatives
  • Neoplasms* / chemically induced
  • Neoplasms* / complications
  • Neoplasms* / drug therapy
  • Opioid-Induced Constipation*
  • Retrospective Studies

Substances

  • Analgesics, Opioid
  • naldemedine
  • Naltrexone