Therapeutic Classification: anti-Alzheimers's agents
Pharmacologic Classification: cholinergics (cholinesterase inhibitors)
Absorption: Well absorbed after oral administration. Bioavailability of transdermal formulation comparable to that of oral tablets.
Distribution: Widely distributed to extravascular tissues.
Protein Binding: 96%.
Metabolism/Excretion: Partially metabolized by the liver (CYP2D6 and CYP3A4 isoenyzmes) and partially excreted by kidneys (17% unchanged). Two metabolites are pharmacologically active. The CYP2D6 enzyme system exhibits genetic polymorphism (∼7% of population may be poor metabolizers and may have significantly ↑ donepezil concentrations and an ↑ risk of adverse effects).
Half-Life: Oral: 70 hr. Transdermal: 91 hr.
(improvement in symptoms)
| ROUTE | ONSET | PEAK | DURATION |
|---|
| PO | unknown | several wk | 6 wk‡ |
| Transdermal | unknown | several wk | 6 wk‡ |
Mild to Moderate Alzheimer's Disease
- PO (Adults ): 5 mg once daily; may ↑ to 10 mg once daily after 4–6 wk (dose should not exceed 5 mg/day in frail, elderly females).
- Transdermal (Adults ): Apply one 5 mg/day transdermal system once weekly; may ↑ to one 10 mg/day transdermal system once weekly after 4–6 wk. Switching from oral to transdermal donepezil: If patient taking 5 mg/day of oral donepezil, switch to one 5 mg/day transdermal system applied once weekly; if receiving 5 mg/day of oral donepezil for ≥4–6 wk, can switch to one 10 mg/day transdermal system applied once weekly. If patient taking 10 mg/day of oral donepezil, switch to one 10 mg/day transdermal system applied once weekly.
Severe Alzheimer's Disease
- PO (Adults ): 5 mg once daily; may ↑ to 10 mg once daily after 4–6 wk; after 3 mo, may then ↑ to 23 mg once daily.
- Transdermal (Adults ): Apply one 5 mg/day transdermal system once weekly; may ↑ to one 10 mg/day transdermal system once weekly after 4–6 wk. Switching from oral to transdermal donepezil: If patient taking 5 mg/day of oral donepezil, switch to one 5 mg/day transdermal system applied once weekly; if receiving 5 mg/day of oral donepezil for ≥4–6 wk, can switch to one 10 mg/day transdermal system applied once weekly. If patient taking 10 mg/day of oral donepezil, switch to one 10 mg/day transdermal system applied once weekly.
