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Switch From Donepezil Tablets to Rivastigmine Transdermal Patch Safe in Alzheimer's Disease: Presented at AGS

By Crina Frincu-Mallos, PhD

WASHINGTON, DC -- May 12, 2008 -- Switching medications is an option for patients who do not adhere to prescribed treatment due to tolerability issues, lack of initial efficacy, or loss of efficacy when the drug is taken for a long time.

For patients with Alzheimer's disease who are noncompliant with their treatment regimen, treatment with donepezil tablets alone or in combination with memantine can be switched safely to the rivastigmine transdermal patch without a washout period.

Lead author Gus Alva, MD, Medical Director, ATP Clinical Research, Costa Mesa, California, and colleagues reported their findings here in a poster presentation at the 2008 Annual Scientific Meeting of the American Geriatrics Society (AGS).

"The transdermal patch of rivastigmine is as efficacious as the highest dose of rivastigmine capsules [6 mg, given twice daily], while its use results in approximately one third the gastrointestinal toxicities observed with the capsules," said Dr. Alva.

As part of the open-label, randomised, multicentre, parallel-group Switch From Aricept to Patch (SWAP) study, Dr. Alva and colleagues enrolled 262 patients with Alzheimer's disease, mean age 77 years. Men and women were enrolled in a 2:3 ratio. The mean duration of dementia for patients on trial was 4 years.

The researchers aimed to assess the tolerability and safety of switching from donepezil tablets, given as a single-agent or in combination with memantine, to rivastigmine transdermal patch.

The study included a 28-day screening phase, after which the patients were randomised to a 5-week core phase consisting of an immediate-switch arm in 131 patients and a delayed-switch arm in 130 patients. One patient in the delayed-switch group chose to discontinue treatment during the baseline visit.

Patients in the immediate-switch arm replaced the donepezil tablets 5 to 10 mg daily with the rivastigmine transdermal patch 4.6 mg/24 hours, while patients on the delayed-switch arm replaced the medications after a 7-day washout period.

Patients receiving memantine in combination with donepezil at day 1 were allowed to continue with the same dose of memantine throughout the study; they represented fewer than half of the total number of patients in the study.

"The rivastigmine transdermal patch was generally well tolerated by patients in both treatment groups," said Dr. Alva, adding that "a total of 36 [27.5%] patients in the immediate-switch group and 45 [34.6%] patients in the delayed-switch group experienced at least 1 adverse event (AE) during the 5-week core phase."

However, 2 patients in the immediate-switch group experienced serious AEs -- lethargy and bradycardia, respectively; both AEs were considered by the investigators to be related to the study medications.

The most frequent AEs in the immediate-switch group were nausea (n = 5); decreased appetite (n = 4); bradycardia, hallucination, agitation (n = 3); and somnolence (n = 2).

The most frequent AEs in the delayed-switch group were constipation (n = 6), application-site reaction (n = 5), somnolence (n = 4), agitation (n = 3), and nausea (n = 1).

"With the exception of 1 case of moderate dermatitis, these AEs were all mild in severity," said Dr. Alva, and mean values for heart rate, supine pulse rate, and systolic and diastolic blood pressure were small and not clinically meaningful in both switch paradigm groups.

Eleven patients in the immediate-switch arm and 10 patients in the delayed-switch arm discontinued treatment, mostly due to adverse events, the researchers noted.

In terms of efficacy, patients in the immediate-switch group had a mean score of 3.9 on the Clinical Global Impression of Change scale, compared with 4.0 in the other group, and the difference was neither statistically nor clinically meaningful, noted Dr. Alva.

"The difference in AEs reported between treatment groups suggests that there may be a subset of patients, with low body weight or with cardiac conduction problems, for whom a delayed switch should be considered," concluded Dr. Alva.

Funding for this study was provided by Novartis Pharmaceuticals Corporation.


[Presentation title: SWAP: The Safety and Tolerability of Switching From Donepezil Tablets to Rivastigmine Transdermal Patch in Alzheimer's Disease. Abstract B37]

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