Background: Donepezil 23 mg is considered for Alzheimer’s disease (AD) to optimize cognitive benefits; however, increased adverse events (AEs) can negatively influence drug adherence. We investigated whether body weight (BW) differs based on the presence of AEs, and which baseline factors were relevant to the safety of high-dose donepezil. Methods: This study was a post hoc analysis of a multicenter randomized trial between 2014 and 2016. We included patients with moderate to severe AD treated with 10 mg/day of donepezil, and the daily dose was escalated to 23 mg with/without dose titration. Dose titration indicates 15 mg/day of donepezil before escalation or 10 mg and 23 mg/day on alternate days before escalation during the first 4 weeks. The patients were divided into 2 groups based on occurrence of AEs of special interest (AESIs) to compare baseline characteristics. We also assessed relationships between BW and AESIs. Results: Among the 160 participants in the safety population, the baseline BWs differed between the AESI (+) (n = 67) and AESI (−) (n = 93) groups. Baseline BW was inversely correlated with the occurrence of AESIs (p = 0.020), and this relationship was prominent in the no-dose titration group (p = 0.009) but absent in the dose-titration groups (p #x3e; 0.05). Conclusions: BW is the most important factor that correlated with cholinergic AEs. Hence, stepwise dose titration should be considered, particularly in patients with low BW, to minimize the inverse relationship between BW and the occurrence of AEs (“Clinicaltrials.gov” No. NCT02550665 registered on September 15, 2015).
Dement Geriatr Cogn Disord

中文翻译：

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体重对大剂量多奈哌齐治疗阿尔茨海默病安全性的影响：一项多中心、随机、开放标签、平行设计、三臂临床试验的事后分析

背景：多奈哌齐 23 mg 被认为用于治疗阿尔茨海默病 (AD) 以优化认知益处；然而，增加的不良事件 (AE) 会对药物依从性产生负面影响。我们调查了体重 (BW) 是否因 AE 的存在而不同，以及哪些基线因素与高剂量多奈哌齐的安全性相关。方法：本研究是对 2014 年至 2016 年间多中心随机试验的事后分析。我们纳入了接受 10 毫克/天多奈哌齐治疗的中度至重度 AD 患者，并将每日剂量增加至 23 毫克，并进行剂量滴定。剂量滴定表示在前 4 周内，在递增前 15 毫克/天或在递增前的隔天服用 10 毫克和 23 毫克/天。根据特殊关注的 AE (AESIs) 的发生情况将患者分为 2 组，以比较基线特征。我们还评估了 BW 和 AESI 之间的关系。结果：在安全人群的 160 名参与者中，AESI (+) ( n = 67) 和 AESI (-) ( n= 93) 组。基线 BW 与 AESIs 的发生呈负相关 ( p = 0.020)，这种关系在无剂量滴定组 ( p = 0.009) 中很突出，但在剂量滴定组中不存在 ( p #x3e; 0.05)。结论： BW 是与胆碱能 AE 相关的最重要因素。因此，应考虑逐步剂量滴定，特别是对于低 BW 的患者，以尽量减少 BW 与 AE 发生之间的反比关系（“Clinicaltrials.gov”No. NCT02550665，2015 年 9 月 15 日注册）。
老年痴呆症认知障碍