Department of Hospital Pharmacy, Nagasaki University Hospital.
Nagasaki University Palliative Care Center.
Biol Pharm Bull. 2021;44(8):1081-1087. doi: 10.1248/bpb.b21-00209.
Naldemedine (NAL), a peripherally acting μ-opioid receptor antagonist, is effective for opioid-induced constipation (OIC). However, diarrhea is the most common adverse event. We investigated the incidence of NAL-induced diarrhea in patients who started NAL at Nagasaki University Hospital between June 2017 and March 2019. Predictors of NAL-induced diarrhea were analyzed using a multivariate logistic regression model. Two hundred and forty-two patients were included in the present study, and NAL-induced diarrhea was observed in 17.8% (43 patients). The results of multiple logistic regression analyses identified the administration of opioid analgesics for 8 d or longer before the initiation of NAL (odds ratio (OR): 2.20, 95% confidence interval (95% CI): 1.04-4.64, p = 0.039), the combination of a laxative (OR: 2.22, 95%CI: 1.03-4.81, p = 0.042), and the combination of CYP3A4 inhibitors (strong/moderate) (OR: 2.80, 95%CI: 1.02-7.67, p = 0.045) as risk factors. Therefore, the development of diarrhea needs to be considered in patients with these risk factors. Furthermore, diarrhea may be controlled by the initiation of NAL within 7 d of opioid analgesics and, where possible, the discontinuation of or change in the combination of moderate or strong CYP3A4 inhibitors.
纳洛美丁（NAL）是一种外周作用μ-阿片受体拮抗剂，对阿片类药物引起的便秘（OIC）有效。然而，腹泻是最常见的不良反应。我们调查了 2017 年 6 月至 2019 年 3 月期间在长崎大学医院开始使用 NAL 的患者中 NAL 引起的腹泻的发生率。使用多变量逻辑回归模型分析了 NAL 引起的腹泻的预测因素。本研究共纳入 242 例患者，其中 17.8%（43 例）出现 NAL 引起的腹泻。多变量逻辑回归分析的结果表明，在开始使用 NAL 之前，阿片类镇痛药的使用时间为 8 天或更长时间（比值比（OR）：2.20，95%置信区间（95%CI）：1.04-4.64，p=0.039），联合使用泻药（OR：2.22，95%CI：1.03-4.81，p=0.042），以及联合使用 CYP3A4 抑制剂（强/中度）（OR：2.80，95%CI：1.02-7.67，p=0.045）是危险因素。因此，需要考虑这些危险因素的患者腹泻的发展。此外，通过在阿片类镇痛药开始后 7 天内开始使用 NAL，以及尽可能停用或更换中度或强 CYP3A4 抑制剂的联合治疗，可能控制腹泻。
