Weekly transdermal donepezil equally effective, more tolerable than daily oral therapy

SAN DIEGO — A once-weekly dose of transdermal donepezil proved a safe and effective equivalent to a daily dose of oral donepezil for Alzheimer’s-related dementia, per a presenter at the Alzheimer’s Association International Conference.

“Donepezil, a reversible acetylcholinesterase inhibitor, is the most prescribed medication for the treatment of dementia of the Alzheimer’s type in patients with mild, moderate and severe disease,” Pierre N. Tariot, of Banner Alzheimer’s Institute in Phoenix, noted in his poster presentation.

Tariot and fellow researchers sought to examine the bioequivalence as well as the safety and efficacy of transdermal donepezil (Adlarity, Corium) dosage once a week compared with a once-daily oral dosage in a cohort of healthy adults.

The researchers conducted an open-label, randomized, crossover, three-period trial with 60 volunteer participants aged 18 to 55 years. All participants received 5 mg per day of transdermal donepezil during the 5-week period 1, followed by 10 mg per day of transdermal donepezil or 10 mg per day of oral donepezil in the 5-week period 2; treatments were switched in period 3. Bioequivalence was assessed at steady state in week 5 of each treatment. Safety and tolerability were also evaluated.

Results showed that, at steady state, adjusted geometric mean ratios (aGMR; % [90% CI]) of transdermal donepezil to oral donepezil for maximum plasma concentration and area under the plasma concentration versus time curve (0 to 168 hours) were 88.7 (81.7 to 96.2) and 108.6 (100.5 to 117.4) for 10 mg per day and 86.1 (79.8 to 92.9) and 105.3 (97.6 to 113.6) for 5 mg per day of transdermal donepezil. The 90% CIs for the GMRs were generally within the accepted 80% to 125% range for establishing bioequivalence. Adverse events were reported in 80% of participants: 53.3% for the 5 mg per dday transdermal donepezil, 54.5% for the 10 mg per day transdermal donepezil and 57.1% for oral donepezil.

Data additionally revealed that, except for abdominal pain (5.5% vs 1.8%), fewer gastrointestinal adverse events were reported with 10 mg per day of transdermal than oral donepezil (constipation, 5.5% vs. 17.9%; nausea 1.8% vs. 30.4%; diarrhea 3.6% vs. 12.5%), respectively. There were also fewer adverse events of dizziness (3.6% vs. 19.6%) and no incidence of somnolence (0 vs. 10.7%) reported with transdermal. No serious adverse events, or those leading to treatment discontinuation or death were reported.

“Study results demonstrated that convenient once-weekly Adlarity offers significant potential benefit to patients and caregivers because it is equivalent to an oral pill taken daily but offers a lower risk of troublesome GI side effects,” Charles Oh, MD, chief medical officer of Corium, said in a release that accompanied the study.

• References:
• 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. Published Aug. 1, 2022. Accessed Aug. 3, 2022.