Adverse drug events affecting medication persistence with rivastigmine patch application

Takashi Osada,1 Norio Watanabe,1 Naomitsu Asano,2 Yuzo Adachi,2 Keiko Yamamura1 1Clinical Pharmacy, School of Pharmacy, Aichi Gakuin University, Nagoya, Aichi, Japan; 2Sasayuri Pharmacy, Toki, Gifu, Japan Purpose: 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. Participants and methods: 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. Results: 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%). Conclusion: 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. Keywords: rivastigmine patch, application site reactions, medication persistence, community pharmacy, Alzheimer’s diseas