Lee et al evaluated adverse effects associated with sustained-release donepezil in elderly Koreans with moderate to severe Alzheimer disease. They found that a lower body mass index was associated a higher rate of treatment-emergent adverse events (TEAE). The authors are from multiple universities in Korea and Duke University.
Patient selection: elderly Korean adults with moderate to severe Alzheimer disease
Dose of sustained-release (SR) donepezil: 23 mg per day
Donepezil was started at 5 mg per day in an immediate release (IR) formulation, then increased to 10 mg per day after 1 month. After 3 months at 10 mg per day of the immediate release formulation the patient could be switched to the sustained release (SR) formulation, with dose up to 23 mg per day.
Outcome: treatment-emergent adverse events (TEAE), which were adverse events that appeared or that got worse after the drug was started. These need not have a causal relationship with donepezil.
Most common treatment-emergent adverse events in the first 24 weeks:
(1) nausea
(2) decreased appetite
(3) dizziness
The rate of these adverse events was higher in patients with a low or normal body mass index (not overweight), with body mass index < 23 kg per square meter. Patients with higher BMI's also experienced these adverse events but at a lower rate.
The rate of serious TEAE (disability, hospitalization, permanent damage, emergency department visit, death) was comparable in the 2 groups at about 6.5%.
Additional factors that may contribute to adverse events which were excluded in the study design:
(1) drugs or foods known to interfere with donepezil metabolism
(2) drugs known to cause sedation or alertness
(3) drugs with anticholinergic effect
