Factors associated with non-response to naldemedine for opioid-induced constipation in cancer patients: A subgroup analysis

Abstract

Background Opioid-induced constipation (OIC) is one of the most common adverse events of opioid therapy and can severely reduce quality of life (QOL). Naldemedine is the orally available peripheral-acting μ-opioid receptor antagonist approved for OIC treatment. However in daily clinical practice, some cancer patients show insufficient control of OIC even while receiving naldemedine. Objective To identify factors associated with non-response to naldemedine in cancer patients. Methods This study retrospectively analyzed 127 cancer patients prescribed naldemedine at Seirei Hamamatsu General Hospital in Japan between November 2016 and June 2021. For the regression analysis of factors associated with OIC, variables were extracted manually from electronic medical records. Naldemedine had been prescribed by the attending physician after the presence of OIC had been defined with reference to Rome IV diagnostic criteria. Naldemedine was evaluated as “effective” in cases where the number of defecations increased at least once in the first 3 days after starting naldemedine. Multivariate logistic regression analysis was performed to identify factors associated with non-response to naldemedine. The data used were from the group of patients who received naldemedine in our previous study. Results Factors significantly associated with non-response to naldemedine included chemotherapy with taxanes within 1 month of evaluation of naldemedine effect (odds ratio [OR] = 0.063; 95% confidence interval [CI] = 0.007–0.568), and addition of or switching to naldemedine due to insufficient efficacy of prior laxatives (OR = 0.352, 95% CI = 0.129–0.966). Conclusion The identification of factors associated with non-response to naldemedine prescribed for OIC may help improve QOL among cancer patients.

Impacts of genetic polymorphisms and cancer cachexia on naldemedine pharmacokinetics and bowel movements in patients receiving opioid analgesics

“…In the present study, these variants might have had little effect on naldemedine binding to OPRM1 and did not affect the naldemedine efficacy. Earlier naldemedine administration after starting opioid analgesics is needed to obtain an improvement in defecation, which is consistent with earlier reports [42]. Lower SBM responders among patients with concomitant laxatives reflected lower plasma naldemedine caused by magnesium oxide.…”

Naldemedine and Magnesium Oxide as First-Line Medications for Opioid-Induced Constipation: A Comparative Database Study in Japanese Patients With Cancer Pain

“…There are many factors causing constipation in patients with cancer, and magnesium oxide is possibly effective in treating constipation other than OIC, explaining the fewer prescription changes compared with naldemedine. For instance, it is worth noting that chemotherapy with taxanes within one month of naldemedine initiation is a significant risk for OIC [ 24 ] and is significantly associated with non-responsiveness to naldemedine [ 25 ]. High body mass index and lack of appropriate MOR antagonists early in the opioid treatment are additional risk factors for OIC [ 24 ].…”