Adlarity: A New Way to Deliver Donepezil

About 6.5 million Americans over 65 have Alzheimer disease and that number’s expected to balloon to 14 million by 2060.1 Many transition to hospice services, so hospice clinicians are sure to encounter patients taking the latest branded medications. One is a drug approved by the U.S. Food and Drug Administration (FDA) in March 2022 called Adlarity.1-3 While it’s not the first transdermal acetylcholinesterase inhibitor (AChEI), it’s the first non-oral donepezil formulation. Like its oral counterpart, it’s approved for patients with mild to severe Alzheimer disease.1-4

In late September 2022, Corium, Inc. announced Adlarity’s availability from drug wholesalers with a more widespread national launch anticipated in 2023.1 Corium also expects Adlarity to be covered under Medicare Part D plans in 2023. So, it’s something for hospice practitioners to have on their radar, since they may soon come across patients using Adlarity in the community.1

Adlarity’s approval and subsequent release was based on results from a relative bioavailability study.3 It evaluated the bioequivalence of steady-state transdermal and oral donepezil in 60 healthy individuals aged 18-55.3-5 It’s unclear how this study might translate to elderly Alzheimer disease patients with multiple comorbidities.

Transdermal donepezil is touted as being advantageous over oral donepezil for patients with barriers to adherence, those who experience intolerable GI adverse effects with the oral form, or those who have difficulty swallowing tablets.1-3 Notably, transdermal rivastigmine was specifically developed to, and effectively does, reduce adverse effects/improve tolerance versus the oral form. However, even if the same holds true for donepezil and the transdermal formulation is better tolerated than its oral counterpart, the relative magnitude of the difference may be of debatable clinical relevance as the incidence of adverse effects with oral donepezil is already markedly lower than either oral rivastigmine or galantamine and is similar to that of the less expensive, generically available, transdermal rivastigmine.

Like other AChEIs, Adlarity should typically be considered for deprescribing in terminally ill patients, particularly in cases of intolerable adverse effects (e.g., diarrhea, nausea, vomiting, incontinence, weight loss, or bradycardia), drug-drug or drug-disease interactions, severe cognitive impairment, institutionalization, or patient/family preference.6 When stopping an AChEI, a tapered discontinuation approach is recommended when possible.6

In terms of deprescribing transdermal formulations, they inherently facilitate a natural taper because drug remains in systemic circulation and drug serum levels would be expected to gradually decline following patch removal. Dysphagia preventing a hospice patient from swallowing oral donepezil should be a cue to deprescribe, rather than switch to a transdermal product.

Adlarity is expensive (AWP $540 per 28 days)7, so if the hospice interdisciplinary team and patient caregivers agree that continued use of an AChEI is warranted, transdermal rivastigmine or oral donepezil should be considered as therapeutic alternatives.

Written by:

John Corrigan, PharmD

Clinical Pharmacist, OnePoint Patient Care

John’s primary responsibilities as a clinical pharmacist at OnePoint Patient Care are staff and partner education, medication utilization reviews, and assisting with formulary development and maintenance. He attended the University of Iowa for both undergraduate studies and pharmacy school. He earned a PharmD from the University of Iowa College of Pharmacy in 2013. He was first introduced to hospice and OnePoint Patient Care as a 4th year pharmacy student, completing a 5-week elective clinical hospice pharmacy rotation. He started his employment with OnePoint Patient Care as a staff pharmacist in 2014. He transitioned to his current role, as a clinical pharmacist, in the spring of 2019.

References

  1. Corium, Inc. Corium Launces Adlarity (donepezil transdermal system) for Patients with Alzheimer’s Dementia. Cision PR Newswire. September 29, 2022. Accessed October 10, 2022. https://www.prnewswire.com/news-releases/corium-launches-adlarity-donepezil-transdermal-system-for-patients-with-alzheimers-dementia-301636317.html
  2. Corium, Inc. Corium Announces Publication of Adlarity (donepezil transdermal system) Clinical Trial Data: Drug Exposure Equivalent to Oral Donepezil With Favorable GI Side Effect Profile. Cision PR Newswire. September, 19, 2022. Accessed October 10, 2022. https://www.prnewswire.com/news-releases/corium-announces-publication-of-adlarity-donepezil-transdermal-system-clinical-trial-data-drug-exposure-equivalent-to-oral-donepezil-with-favorable-gi-side-effect-profile-301626829.html
  3. Corium, Inc. Corium’s New Once-Weekly Transdermal Alzheimer’s Dementia Therapy Adlarity (donepezil transdermal system) Provides Drug Delivery Equivalent to Oral Donepezil With Favorable GI Side Effect Profile. Cision PR Newswire. August 1, 2022. Accessed October 10, 2022. https://www.prnewswire.com/news-releases/coriums-new-once-weekly-transdermal-alzheimers-dementia-therapy-adlarity-donepezil-transdermal-system-provides-drug-delivery-equivalent-to-oral-donepezil-with-favorable-gi-side-effect-profile
  4. Package insert. Corium; 2022. Accessed October 19, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212304s000lbl.pdf
  5. Tariot P, Braeckman R, Oh C. Comparison of Steady-State Pharmacokinetics of Donepezil Transdermal Delivery System with Oral Donepezil. Journal of Alzheimer’ Disease. 2022;pre-press:1-12. doi:32333/JAD-220530
  6. Hospice Medication Deprescribing Toolkit. NHPCO. November 2020; version 1.0:11-14. https://www.nhpco.org/resources/publications/
  7. Accessed October 19, 2022.