BACKGROUND Naldemedine, a novel peripherally-acting mu-opioid receptor antagonist, has improved opioid-induced constipation in randomized controlled trials. The most frequent adverse event of naldemedine is diarrhea, which can cause abdominal pain and often leads to treatment discontinuation. We aimed to identify risk factors and appropriate management strategies for key adverse events including diarrhea associated with naldemedine, since those have not been extensively studied. METHODS We conducted a multi-center retrospective cohort study. Eligible patients had cancer, had undergone palliative care at participating centers, had been prescribed regular opioids, and had taken at least one dose of naldemedine between June 2017 and March 2018. The primary endpoint was the incidence of diarrhea according to baseline characteristics. Secondary endpoints included the duration of naldemedine administration, daily defecation counts before and after starting naldemedine, duration and severity of diarrhea as an adverse event of naldemedine, other adverse events, and the incidence of constipation within 7 days after recovery from diarrhea. We defined patients who started naldemedine within three days of starting a regularly prescribed opioid as the early group, and the remainder as the late group. RESULTS Among 103 patients who received naldemedine, 98 fulfilled the eligibility criteria. The median age was 68 years and 48% of the patients were female. Median performance status was 3, and the median oral intake was 50%. The median duration of naldemedine administration and overall survival were 25 and 64 days, respectively. The incidence of diarrhea in the early group (n = 26) was significantly lower than in the late group (n = 72) (3.9% vs. 22.2%, p = 0.02). Daily defecation counts increased after late (median 0.43 to 0.88, p < 0.001), but remained stable after early naldemedine administration (median 1.00 to 1.00, p = 0.34). Constipation after the diarrhea was resolved was common (53%), especially among patients who stopped naldemedine (78%). The diarrhea was improved within three days in 92% of patients who stopped other laxatives. CONCLUSIONS The early administration of naldemedine is beneficial because it reduces adverse events including diarrhea. Diarrhea caused by naldemedine can be effectively managed by stopping other laxatives while continuing naldemedine.

中文翻译：

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接受阿片类药物的患者中与纳尔德米定相关的腹泻的预防和管理：一项回顾性队列研究。


背景 Naldemedine 是一种新型外周作用的 mu-阿片受体拮抗剂，在随机对照试验中改善了阿片类药物引起的便秘。纳尔德米定最常见的不良事件是腹泻，它会引起腹痛，并常常导致治疗停止。我们的目的是确定关键不良事件的风险因素和适当的管理策略，包括与纳尔德米定相关的腹泻，因为这些不良事件尚未得到广泛研究。方法我们进行了一项多中心回顾性队列研究。符合条件的患者患有癌症，在参与中心接受过姑息治疗，定期服用阿片类药物，并在 2017 年 6 月至 2018 年 3 月期间至少服用过一剂纳尔德米定。主要终点是根据基线特征的腹泻发生率。次要终点包括纳尔德米定给药的持续时间、开始使用纳尔德米定之前和之后的每日排便次数、作为纳尔德米定不良事件的腹泻的持续时间和严重程度、其他不良事件以及腹泻恢复后7天内便秘的发生率。我们将在开始定期服用阿片类药物后三天内开始使用纳尔德米定的患者定义为早期组，其余患者定义为晚期组。结果 在接受 naldemedine 治疗的 103 名患者中，98 名患者符合资格标准。中位年龄为 68 岁，48% 的患者为女性。中位表现状态为 3，中位口服摄入量为 50%。纳尔德米定给药的中位持续时间和总生存期分别为 25 天和 64 天。早期组（n = 26）腹泻发生率显着低于晚期组（n = 72）（3.9% vs. 22.2%，p = 0.02）。 每日排便次数晚后增加（中位数 0.43 至 0.88，p < 0.001），但早期给予纳尔德米定后保持稳定（中位数 1.00 至 1.00，p = 0.34）。腹泻缓解后便秘很常见（53%），特别是在停止服用纳尔德米定的患者中（78%）。停止其他泻药后，92% 的患者三天内腹泻得到改善。结论 早期服用纳尔德米定是有益的，因为它可以减少腹泻等不良事件。纳尔德米定引起的腹泻可以通过停止其他泻药同时继续使用纳尔德米定来有效控制。