Osada Takashi, Watanabe Norio, Asano Naomitsu, Adachi Yuzo, Yamamura Keiko
Clinical Pharmacy, School of Pharmacy, Aichi Gakuin University, Nagoya, Aichi, Japan,
Sasayuri Pharmacy, Toki, Gifu, Japan.
Patient Prefer Adherence. 2018 Jul 18;12:1247-1252. doi: 10.2147/PPA.S166680. eCollection 2018.
The rivastigmine transdermal patch, the only existing cholinesterase inhibitor available as a transdermal delivery system for treating Alzheimer's disease, has been reported to inhibit progression of cognitive impairment and impairment in activities of daily living, in addition to reducing care burden and improving adherence. However, application of the rivastigmine patch also frequently results in erythema, pruritus, contact dermatitis, and other cutaneous adverse events at the application site, making it difficult to increase the effective dose and continue treatment. Therefore, we conducted a survey to examine the manifestation of adverse events and medication persistence in patients who were prescribed the rivastigmine patch.
Three hundred and twelve patients diagnosed with Alzheimer's disease between July 1, 2011 and March 31, 2015 at the Toki Medical Clinic and who were prescribed a rivastigmine patch at the Sasayuri Community Pharmacy were involved in the study. Outcomes such as manifestation of adverse events, dose at manifestation, and dose reduction as well as discontinuation were retrospectively examined through medication counseling records.
Adverse drug events developed in 209 of the 312 patients (67.0%). Approximately 70% of patients who developed adverse events did so before reaching the maintenance dose of 18 mg. The main adverse drug events were cutaneous reactions at the application site such as rash and erythema in 186 patients (59.6%) and gastrointestinal disorders such as nausea, vomiting, and diarrhea in 29 patients (9.3%). Also, of the 312 patients, 118 patients (37.8%) discontinued the rivastigmine patch; reasons for discontinuation included cutaneous application site reactions in 74 patients (62.7%), gastrointestinal disorders in 5 patients (4.2%), and psychiatric disorders in 6 patients (5.1%). Among the 74 patients who discontinued the rivastigmine patch due to application site disorders, the dose at the time of discontinuation was 4.5 mg in 22 patients (29.7%), 9 mg in 37 patients (50.0%), 13.5 mg in 10 patients (13.5%), and 18 mg in 5 patients (6.8%).
Approximately 60% of patients who used the rivastigmine patch developed application site reactions, suggesting difficulty in increasing the dose to the effective dose and in continuing application. Also, ~80% of the patients who discontinued the rivastigmine patch due to application site reactions developed these reactions when the dose was increased to 9 mg.
卡巴拉汀透皮贴剂是目前唯一可用于治疗阿尔茨海默病的透皮给药系统的胆碱酯酶抑制剂，据报道，它除了可减轻护理负担和提高依从性外，还能抑制认知功能障碍的进展以及日常生活活动能力的减退。然而，使用卡巴拉汀贴剂也经常会在用药部位导致红斑、瘙痒、接触性皮炎和其他皮肤不良事件，使得难以增加有效剂量并持续治疗。因此，我们进行了一项调查，以研究使用卡巴拉汀贴剂的患者中不良事件的表现和药物持续性。
2011年7月1日至2015年3月31日期间在土岐医疗诊所被诊断为阿尔茨海默病且在笹百合社区药房开具了卡巴拉汀贴剂处方的312例患者参与了本研究。通过用药咨询记录回顾性研究不良事件的表现、出现不良事件时的剂量、剂量减少以及停药等结果。
312例患者中有209例（67.0%）发生了药物不良事件。发生不良事件的患者中约70%在达到18mg维持剂量之前就出现了不良事件。主要的药物不良事件是用药部位的皮肤反应，如186例患者（59.6%）出现皮疹和红斑，以及29例患者（9.3%）出现胃肠道紊乱，如恶心、呕吐和腹泻。此外，在312例患者中，118例患者（37.8%）停用了卡巴拉汀贴剂；停药原因包括74例患者（62.7%）的用药部位皮肤反应、5例患者（4.2%）的胃肠道紊乱和6例患者（5.1%）的精神障碍。在因用药部位疾病停用卡巴拉汀贴剂的74例患者中，停药时的剂量为4.5mg的有22例（29.7%），9mg的有37例（50.0%），13.5mg的有10例（13.5%），18mg的有5例（6.8%）。
使用卡巴拉汀贴剂的患者中约60%出现了用药部位反应，这表明难以将剂量增加到有效剂量并持续用药。此外，因用药部位反应停用卡巴拉汀贴剂的患者中约80%在剂量增加到9mg时出现了这些反应。
