What is the recommended dose titration for Aricept (donepezil)?

Donepezil (Aricept) Dose Titration Protocol

The recommended dose titration for donepezil (Aricept) begins with 5 mg once daily in the evening for 4-6 weeks, then increasing to 10 mg once daily if well tolerated, with a potential increase to 23 mg daily after at least 3 months on 10 mg for patients with moderate to severe Alzheimer's disease. 1

Initial Dosing and Titration Schedule

Mild to Moderate Alzheimer's Disease

• Starting dose: 5 mg once daily in the evening, just prior to retiring
• Titration: After 4-6 weeks on 5 mg daily, may increase to 10 mg daily if well tolerated
• Maximum dose: 10 mg once daily 1

Moderate to Severe Alzheimer's Disease

• Starting dose: Same as above (5 mg once daily)
• First titration: After 4-6 weeks on 5 mg daily, may increase to 10 mg daily
• Second titration: After at least 3 months on 10 mg daily, may increase to 23 mg daily
• Maximum dose: 23 mg once daily 1

Administration Guidelines

• Take in the evening, just prior to retiring
• Can be taken with or without food
• The 5 mg and 10 mg tablets can be split if needed
• The 23 mg tablet should NOT be split, crushed, or chewed 1

Monitoring and Dose Adjustments

Efficacy Assessment

• Evaluate beneficial response after 6-12 months of treatment 2
• Consider discontinuation if:
  • Side effects develop and don't resolve
  • Continued deterioration at pre-treatment rate after 6-12 months

Special Populations

• Hepatic impairment:
  • No dose adjustment needed for mild to moderate hepatic disease
  • More caution and potentially lower dosing for severe hepatic impairment
  • Donepezil has no significant hepatotoxicity, unlike some other cholinesterase inhibitors 2, 3
• Renal impairment: No specific dose adjustments required in the FDA labeling

Side Effect Management

Common Side Effects

• Gastrointestinal: nausea, vomiting, diarrhea (more common with 10 mg than 5 mg, and more common with 23 mg than 10 mg) 1
• Neurological: dizziness, headache, insomnia 3

Minimizing Side Effects

• The 6-week titration period (rather than faster titration) helps minimize cholinergic side effects 3
• Taking the medication in the evening may reduce the impact of side effects
• If side effects are problematic at 10 mg, consider returning to 5 mg dose

Clinical Pearls

• Donepezil provides modest but significant benefits in cognitive function, with improvements of 1.9-2.9 points on the ADAS-Cog scale at 24 weeks compared to placebo 2
• Benefits include improved cognition, global clinical function, activities of daily living, and behavioral symptoms 4
• The long half-life (approximately 70 hours) allows for once-daily dosing 5
• Unlike tacrine, donepezil does not require liver function monitoring as it has not shown evidence of hepatotoxicity 3

Common Pitfalls to Avoid

• Titrating too quickly: Increasing the dose before the recommended 4-6 week period can lead to increased cholinergic side effects
• Missing the opportunity for dose escalation: Some patients may benefit from the higher 10 mg dose but are never titrated up from 5 mg
• Inappropriate use of 23 mg dose: The 23 mg dose should only be used after at least 3 months on 10 mg and only for moderate to severe Alzheimer's disease
• Splitting the 23 mg tablet: This tablet has special formulation and should never be split, crushed, or chewed

Donepezil remains a first-line treatment for Alzheimer's disease with a well-established efficacy and safety profile when properly titrated according to this protocol.