Department of Neuropsychiatry, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Hyogo, Japan.
J Alzheimers Dis. 2023;95(4):1535-1543. doi: 10.3233/JAD-230386.
Oral formulations are not suitable for demented patients with dysphagia, those refuse to take tablets, or those with drug compliance problem. However, only oral formulations of donepezil hydrochloride are approved for the treatment of severe Alzheimer's disease in Japan.
To evaluate the safety, tolerability, and efficacy of long-term application of a 55.0 mg transdermal donepezil patch switched from a 10 mg oral donepezil hydrochloride tablet, for the treatment of patients with severe Alzheimer's disease.
A 52-week, multicenter, open-label, uncontrolled (phase III) study (jRCT2080224612) was conducted in Japan between April 2019 and August 2021. A 10 mg donepezil hydrochloride tablet was administered once a day for four weeks; a 55.0 mg donepezil patch was then applied once a day for 52 weeks in patients with severe Alzheimer's disease.
Of 64 patients received the patch, 45 completed the 52-week period. The overall discontinuation rate was 29.7% (19/64). Among the 19 patients discontinued, six patients 9.4% (6/64) discontinued due to adverse events. The incidence of adverse events at application sites was 67.2% (43/64), including application site erythema 29.7% (19/64), application site pruritus 25.0% (16/64), and contact dermatitis 20.3% (13/64). Adverse events were mild and did not increase with time, demonstrating a favorable safety profile. Cognitive function, measured using the Mini-Mental State Examination, was maintained for up to 24 weeks.
Adverse events were considered manageable in a clinical setting. The long-term application of a 55.0 mg donepezil patch once a day was feasible treatment in patients with severe Alzheimer's disease.
对于有吞咽困难的痴呆患者、拒绝服用片剂的患者或有药物依从性问题的患者，口服制剂并不适用。然而，在日本，只有盐酸多奈哌齐的口服制剂被批准用于治疗严重的阿尔茨海默病。
评估将 10mg 盐酸多奈哌齐片转换为 55.0mg 多奈哌齐透皮贴剂长期应用的安全性、耐受性和疗效，用于治疗严重的阿尔茨海默病患者。
在日本进行了一项为期 52 周、多中心、开放标签、非对照（III 期）研究（jRCT2080224612）。对于严重的阿尔茨海默病患者，首先给予 10mg 盐酸多奈哌齐片，每天一次，持续 4 周；然后，每天一次应用 55.0mg 多奈哌齐贴剂，持续 52 周。
在接受贴剂治疗的 64 例患者中，45 例完成了 52 周的治疗。总的停药率为 29.7%（19/64）。在 19 例停药的患者中，有 6 例（6/64）因不良反应停药，占 9.4%。贴剂应用部位不良反应发生率为 67.2%（43/64），包括应用部位红斑 29.7%（19/64）、应用部位瘙痒 25.0%（16/64）和接触性皮炎 20.3%（13/64）。不良反应均为轻度，且不会随时间增加，显示出良好的安全性。使用简易精神状态检查（Mini-Mental State Examination）评估认知功能，直至 24 周时仍保持稳定。
在临床环境中，认为不良反应是可以管理的。对于严重的阿尔茨海默病患者，每天应用 55.0mg 多奈哌齐透皮贴剂是一种可行的治疗方法。
