This study aimed to evaluate the efficacy and potential pharmacological interaction of naldemedine and magnesium oxide (MgO) in the management of opioid-induced constipation (OIC) in cancer patients, with a particular focus on the impact of different MgO doses on treatment outcomes. A total of 171 patients who received opioid therapy were included in this study. The outcome variable was defecation. Daily defecation status during the observation period was extracted from electronic medical records. To assess the effects and potential interaction between naldemedine and MgO on defecation, a generalized estimating equations (GEE) model with a logit link function was used to account for within-patient clustering. Predicted probabilities of defecation were calculated based on the fitted GEE model. The probability of defecation increased with higher doses of MgO. Among patients receiving both MgO and naldemedine, the likelihood of defecation was significantly higher at MgO doses ≤ 1500 mg compared to those receiving MgO alone. However, at doses > 1500 mg, naldemedine did not add further benefit. Naldemedine was independently associated with improved bowel movements, regardless of MgO use. The association between MgO and defecation also strengthened with increasing doses. No significant interaction between naldemedine and MgO was observed at any dose. The concomitant use of MgO and naldemedine was associated with improved defecation, although no statistically significant interaction was detected. However, the added benefit of naldemedine may be limited at higher MgO doses. Naldemedine may be particularly effective in patients with constipation during opioid therapy that is insufficiently responsive to conventional laxatives, especially when an increase in MgO is difficult due to risks such as hypermagnesemia.
Hoshino et al. (Sun,) studied this question.