Aricept (Donepezil) Uptitration Protocol
Donepezil should be started at 5 mg once daily in the evening, and uptitrated to 10 mg once daily only after 4 to 6 weeks of treatment at the lower dose. 1
Standard Uptitration Schedule
- Start with 5 mg once daily taken in the evening, just prior to retiring 1
- Wait 4 to 6 weeks before considering dose escalation 1
- Increase to 10 mg once daily after the 4-6 week stabilization period if the patient tolerates the initial dose 1
- The medication should be taken once daily, not divided into twice-daily dosing 2
Timing Considerations
- Administer in the evening before bedtime according to FDA labeling 1
- However, the American Geriatrics Society recommends morning administration to minimize sleep disturbances 2
- The medication can be taken with or without food 1
Rationale for Gradual Uptitration
The 4-6 week waiting period before dose escalation is critical because:
- Gastrointestinal side effects are dose-dependent, with significantly higher rates at 10 mg compared to 5 mg 3, 4
- Nausea and vomiting occur with a relative risk of 2.54 at higher doses 3
- Diarrhea occurs with a relative risk of 2.57 4
- Anorexia has the largest effect size (relative risk 3.21) among GI symptoms 4
- 70-80% of GI adverse effects occur within the first 2 weeks, and 60-65% resolve within the first month 5
Monitoring During Uptitration
- Monitor for adverse effects particularly during the first 2-4 weeks after each dose change 3
- Watch specifically for nausea, vomiting, diarrhea, anorexia, dizziness, and muscle cramps 3, 4
- Initial agitation may occur but typically subsides after the first few weeks 4
- Monitor for bradycardia or cardiac conduction abnormalities 1
Common Pitfalls to Avoid
- Do not escalate the dose before 4 weeks - this is the most common error and leads to unnecessary discontinuation due to adverse effects 1
- Do not split, crush, or chew tablets (particularly important for the 23 mg formulation, though this is not relevant for standard 5-10 mg dosing) 1
- Do not use twice-daily dosing - donepezil is designed for once-daily administration 2
Special Populations
- Patients with renal impairment may require dose adjustment, making careful uptitration even more important 2
- Elderly patients with multimorbidity should have simplified regimens, reinforcing the once-daily dosing approach 2
Higher Dose Considerations
- For patients with moderate to severe Alzheimer's disease already on 10 mg for at least 3 months, a 23 mg dose may be considered 1
- However, the 23 mg dose has higher adverse event rates with no clear additional benefit over 10 mg 6
- The 10 mg dose provides marginally larger benefits than 5 mg, but with higher withdrawal and adverse event rates 6