By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
The FDA has approved a transdermal system to treat mild, moderate, or severe Alzheimer’s disease (AD). Donepezil, an anticholinesterase (ACH) inhibitor, has been available as an oral form since 1996. The transdermal system (TDS) offers the first once-a-week dosing and the continuous delivery of donepezil. It will be marketed as Adlarity.
INDICATIONS
Donepezil TDS can be prescribed to treat mild, moderate, and severe dementia of the Alzheimer’s type.
DOSAGE
The recommended dose is 5 mg/day applied once weekly. After at least four to six weeks, the dosage may be increased to the maximum recommended dose of 10 mg/day.1 If the patient has been on the 5 mg tablet daily for at least four to six weeks or on 10 mg daily, the recommended starting dose for donepezil TDS is 10 mg/day applied once weekly. Each TDS delivers 5 mg or 10 mg daily for seven days. The system may be applied to the back (avoid the spine), upper buttocks, or upper outer thigh. The site should be alternated every seven days. The same site should not be used again for at least 14 days after removal of a patch. Donepezil TDS is available as 5 mg per day and 10 mg per day.
POTENTIAL ADVANTAGES
The TDS offers more convenient dosing, improved bioavailability, potentially lower adverse effects thanks to less fluctuation in plasma levels, and bypassing gastrointestinal and first pass liver metabolism.2 The other TDS for this indication (rivastigmine) requires daily dosing.
POTENTIAL DISADVANTAGES
Adverse effects unique to TDS are headache (15%), application site pruritus (9%), muscle spasm (9%), and insomnia (7%).1 Skin irritation after patch removal included erythema (64.6%) and papules (16%).1 Cases of skin sensitization were low (four cases in 229 subjects).1
COMMENTS
There are no clinical data on donepezil TDS. FDA approval was based on an open-label study of healthy subjects demonstrating comparable relative bioavailability to the oral form. All subjects received 5 mg donepezil TDS for five weeks, after which subjects received 10 mg TDS or oral donepezil for five weeks. It took three weeks to reach steady state for the TDS.
CLINICAL IMPLICATIONS
AD is a common cause of dementia in older individuals. Current commonly used drugs are limited in their efficacy, including donepezil, rivastigmine, galantamine, and memantine.2 A large Cochrane review of donepezil suggested there is moderate-quality evidence indicating patients with mild, moderate, or severe dementia caused by AD treated for periods of 12 or 24 weeks with donepezil experience small benefits in cognitive function, activities of daily living, and clinician-rated global clinical state.3 Donepezil TDS offers a once-weekly administration. There is no evidence indicating donepezil affects the course of the underlying disease process. Aducanumab, the first drug that targets brain beta-amyloid, has not demonstrated clear clinical benefit. The patch is expected this fall; cost is unavailable.
REFERENCES
- Corium, Inc. Adlarity prescribing information. March 2022.
- Sozio P, Cerasa LS, Marinelli L, Di Stefano A. Transdermal donepezil on the treatment of Alzheimer’s disease. Neuropsychiatr Dis Treat 2012;8:361-368.
- Birks JS, Harvey RJ. Donepezil for dementia due to Alzheimer’s disease. Cochrane Database Syst Rev 2018;6:CD001190.
Donepezil transdermal system can be prescribed to treat mild, moderate, and severe dementia of the Alzheimer’s type.
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