How do you administer Donepezil (Aricept)?

How to Administer Donepezil

Donepezil should be administered as a single 5 mg dose taken orally once daily in the evening just prior to bedtime, with or without food, and increased to 10 mg daily only after 4-6 weeks at the lower dose. 1

Standard Dosing Protocol

Initial Dosing

• Start with 5 mg once daily in the evening, just prior to retiring 1
• Can be taken with or without food 1
• Do not advance to higher doses prematurely 1

Dose Escalation for Mild to Moderate Alzheimer's Disease

• Increase to 10 mg daily only after patients have been on 5 mg for 4-6 weeks 1
• This gradual titration minimizes gastrointestinal adverse effects, which occur in 70-80% of patients within the first 2 weeks but resolve in 60-65% within the first month 2
• The 4-6 week waiting period is critical—shorter escalation schedules (such as 7 days used in some clinical trials) resulted in significantly higher rates of cholinergic side effects 3

Dose Escalation for Moderate to Severe Alzheimer's Disease

• Start at 5 mg daily, advance to 10 mg after 4-6 weeks 1
• Maximum dose of 23 mg daily should not be administered until patients have been on 10 mg for at least 3 months 1
• The 23 mg tablet must not be split, crushed, or chewed 1

Timing Considerations

Evening vs. Morning Administration

• FDA labeling recommends evening administration just prior to bedtime 1
• However, the American Geriatrics Society recommends morning administration to minimize sleep disturbances in patients experiencing insomnia 2
• If sleep disturbances occur with bedtime dosing, consider switching to morning administration 2

Common Adverse Effects to Monitor

Gastrointestinal Effects (Dose-Dependent)

• Nausea (relative risk 2.54), diarrhea (relative risk 2.57), and anorexia (relative risk 3.21) are the most common side effects 4, 2
• These effects are significantly more common at 10 mg compared to 5 mg 2, 5
• Taking with food may reduce gastrointestinal symptoms 5

Other Common Effects

• Muscle cramps, particularly leg cramps (very high relative risk in vascular dementia patients) 4, 2
• Dizziness (relative risk 1.47) 4, 2
• Initial agitation that typically subsides after the first few weeks 6, 5

Special Populations

Renal Impairment

• No specific dose adjustment required in FDA labeling 1
• However, in chronic hemodialysis patients, consider starting at 2.5 mg daily and advancing cautiously, as donepezil is primarily eliminated renally 7
• One case series showed successful use of 2.5-5 mg daily in hemodialysis patients without toxicity 7

Hepatic Impairment

• The 5 mg dose can be given safely to patients with mild-to-moderate hepatic disease 8
• Unlike tacrine, donepezil does not cause hepatotoxicity and does not require liver function monitoring 6, 5

Key Clinical Pitfalls to Avoid

• Do not escalate dose before 4-6 weeks at 5 mg—this is the most common error leading to intolerable side effects 1, 3
• Do not split, crush, or chew the 23 mg tablet 1
• Monitor for bradyarrhythmia, particularly in patients with cardiac conduction abnormalities 6
• Be aware of potential interactions with cimetidine, theophylline, warfarin, and digoxin 6, 5

Monitoring Strategy

• Assess tolerability at 2 weeks (peak time for GI side effects) 2
• Reassess at 4-6 weeks before considering dose escalation 1
• Monitor for cognitive and functional improvement starting at 3 weeks of treatment 3
• No routine laboratory monitoring required (unlike tacrine) 6, 5