Department of Neurology, Xuan Wu Hospital of Capital Medical University, Beijing, China.
Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
J Alzheimers Dis. 2020;74(1):199-211. doi: 10.3233/JAD-190940.
Efficacy and dose-effect relationship of donepezil for treating patients with Alzheimer's disease (AD) have been proven. However, few studies focused on the safety of donepezil, particularly in Chinese patients.
To assess the safety of donepezil 10 mg/day in Chinese patients with mild-to-moderate AD.
In this single-arm, prospective, multicenter trial, 241 patients with mild to moderate AD who had been treated with donepezil 5 mg/day for at least 4 weeks were enrolled. All patients received donepezil 10 mg/day for 20 weeks. Primary outcome was the incidence of adverse events (AEs). Safety profile was evaluated by physical examinations including vital signs and weight, clinical laboratory tests and electrocardiograms, and also correlation analysis between AEs and APOE genotypes.
241 patients were enrolled. Of which, 38.59% patients experienced at least one AE and 17.43% discontinued due to AEs. Most AEs were mild to moderate, with diarrhea, vomiting, and nausea the most frequently reported. Risk of AEs was significantly increased by concomitant use of drugs for cardiovascular and cerebrovascular diseases. Mean changes in heart rate and corrected QT relative to baseline were -1.08±6.02 beat/min (p = 0.009) and -3.91±18.68 ms (p = 0.0062) at week 4 and -1.48 beat/min±7.18 (p = 0.0028) and -0.66 ms±19.66 (p = 0.6561) at week 20, respectively. There were no significant changes in other vital sign parameters. Patients' MMSE scores improved significantly after treatment (p = 0.0038), especially for non-APOEɛ4 allele carriers and patients ≤75 years.
Donepezil 10 mg/day can be tolerated and is effective in Chinese patients with mild-to-moderate AD.
多奈哌齐治疗阿尔茨海默病（AD）患者的疗效和剂量-效应关系已得到证实。然而，很少有研究关注多奈哌齐的安全性，特别是在中国患者中。
评估多奈哌齐 10mg/日治疗轻中度 AD 中国患者的安全性。
这是一项单臂、前瞻性、多中心试验，共纳入 241 例已接受多奈哌齐 5mg/日治疗至少 4 周的轻中度 AD 患者。所有患者均接受多奈哌齐 10mg/日治疗 20 周。主要结局为不良事件（AE）发生率。通过生命体征和体重、临床实验室检查和心电图检查评估安全性，并分析 AE 与 APOE 基因型之间的相关性。
共纳入 241 例患者。其中，38.59%的患者至少发生 1 次 AE，17.43%的患者因 AE 停药。大多数 AE 为轻中度，腹泻、呕吐和恶心最常见。同时使用心血管和脑血管疾病药物会显著增加 AE 风险。与基线相比，治疗 4 周和 20 周时，心率和校正 QT 的平均变化分别为-1.08±6.02 次/分（p=0.009）和-3.91±18.68ms（p=0.0062），-1.48 次/分±7.18（p=0.0028）和-0.66ms±19.66（p=0.6561）。其他生命体征参数无显著变化。治疗后患者 MMSE 评分显著提高（p=0.0038），特别是对于非 APOEɛ4 等位基因携带者和≤75 岁的患者。
多奈哌齐 10mg/日治疗轻中度 AD 中国患者可耐受且有效。
