After being originally approved as a generic medication in 1996, a new transdermal formulation of donepezil is expected to be available for patients with Alzheimer disease in the fall of 2022.
The FDA has approved Corium’s donepezil transdermal system (Adlarity) for the treatment of patients with mild, moderate, or severe Alzheimer disease (AD) dementia, making it the first and only once-weekly patch to continuously deliver consistent doses of donepezil through the skin.1
Donepezil, a centrally acting reversible acetylcholinesterase inhibitor, was approved for medical use in the US in 1996 as a generic medication.2 This new formulation of the medication is delivered directly into a patient’s skin and bypasses the digestive system, resulting in a low possibility of gastrointestinal adverse effects and making it easier for patients with AD and their caregivers to administer the treatment.
The approved dosage is 5 mg/day or 10 mg/day formulations, and patients who were on oral donepezil may switch to once-weekly transdermal system with the help of their prescriber. Expected to be available in early fall 2022, this new formulation was approved pursuant to the FDA’s 505(b)(2) regulatory pathway, with data from multiple clinical trials that demonstrated bioequivalence to donepezil hydrochloride (Aricept; Eisai/Pfizer), which was approved by the FDA for the treatment of severe AD in 2006.
"The availability of a once-weekly patch formulation of donepezil has the potential to substantially benefit patients, caregivers, and healthcare providers,” Pierre N. Tariot, MD, director, Banner Alzheimer’s Institute, said in a statement.1 "It offers effective, well-tolerated and stable dosing for seven days for patients who cannot take daily oral donepezil reliably because of impaired memory. It can also offer benefits for those patients who have diminished ability to swallow or have GI side effects associated with ingestion of oral donepezil."
The therapeutic is the first approved product using Corium’s proprietary CORPLEX transdermal technology, which was developed to provide a sustained, continuous, controlled release of a drug over a period of time. The company noted that it is currently developing other central nervous system (CNS) therapies using this technology, as well.
"The FDA approval of ADLARITY brings to market a new and innovative way to deliver consistently a well-tolerated form of donepezil, the most widely used medicine for patients with Alzheimer's disease," Perry J. Sternberg, president and chief executive officer, Corium, said in a statement.1 “The approval of ADLARITY reinforces the value of Corium's innovative CORPLEX technology, our CNS expertise, and our mission to deliver solutions that transform care for the Alzheimer's community and others impacted by CNS diseases."
Donepezil transdermal system is contraindicated in patients with known hypersensitivity to donepezil or to piperidine derivatives or with a history of allergic contact dermatitis with use of the medication. Warning and precautions of the drug include application site skin reactions, anasthesia, cardiovascular conditions, nausea and vomiting, peptic ulcer disease and gastrointestinal bleeding, genitourinary conditions, seizures, and pulmonary conditions.
Since its approval in the late 1990s, there has been no evidence to suggest that donepezil or other similar agents alter the disease course of AD. One notable study, however, published in the New England Journal of Medicine demonstrated that continued treatment with donepezil is associated with cognitive benefits and sustained functional benefits. Over a 12-month stretch, patients assigned to continue donepezil, as compared to those assigned to discontinue, had a score on the Standardized Mini-Mental State Examination that was higher by an average of 1.9 points (95% CI, 1.3-2.5) and a score on the Bristol Activities of Daily Living that was lower by 3.0 points (95% CI, 1.8-4.3; P <.01 for both comparisons).3