Donepezil Titration Protocol
The recommended titration schedule for donepezil is to start with 5 mg once daily in the evening for 4-6 weeks, then increase to 10 mg once daily if well tolerated, with potential escalation to 23 mg daily after at least 3 months on 10 mg for patients with moderate to severe Alzheimer's disease. 1, 2
Initial Dosing and Titration
- Starting dose: 5 mg once daily in the evening, just prior to retiring 1
- Timing: Take in the evening before bedtime 1
- Administration: Can be taken with or without food 1
- First titration: Increase to 10 mg once daily after 4-6 weeks on 5 mg 1, 2
- Second titration (for moderate-severe AD only): Increase to 23 mg once daily after at least 3 months on 10 mg 1, 2
Titration Considerations
Gastrointestinal Side Effects Management
- Most common adverse effects are gastrointestinal (nausea, vomiting, diarrhea) 2
- These effects typically occur within the first 2 weeks of treatment or dose increase 3
- Taking medication with food can help reduce GI side effects 2
- Slower titration schedules reduce incidence of side effects 4, 3
Alternative Titration Methods for Higher Doses
For patients escalating to 23 mg daily, research suggests intermediate titration methods may improve tolerability:
- Option 1: Increase to 15 mg daily for 4 weeks before escalating to 23 mg 3
- Option 2: Alternate between 10 mg and 23 mg on consecutive days for 4 weeks before full escalation 3
- These intermediate titration steps significantly reduced nausea compared to direct escalation 3
Monitoring During Titration
- Assess for cholinergic side effects: nausea, vomiting, diarrhea, anorexia, headache, insomnia, muscle cramps 2
- Monitor weight, as weight loss can occur 2
- Evaluate for bradycardia, especially in patients with cardiac conditions 5
- Assess for clinical benefit after 6-12 weeks through:
- Physician assessment
- Caregiver reports
- Neuropsychological testing
- Functional changes 2
Special Considerations
- The 23 mg tablet should not be split, crushed, or chewed 1
- Donepezil has a long half-life (60 hours in young adults, 104 hours in elderly) 6
- Side effects are typically mild to moderate and transient 5, 4
- No significant hepatotoxicity concerns (unlike tacrine) 4, 6
- Limited drug interactions, but use caution with strong inducers of cytochrome P450 6
When to Consider Dose Reduction or Discontinuation
- Persistent or severe gastrointestinal side effects 2
- Weight loss >5% from baseline 2
- Poor adherence 2
- Continued deterioration at pre-treatment rate after 6-12 months 2
Following this titration protocol maximizes the potential cognitive and functional benefits of donepezil while minimizing adverse effects that could impact quality of life and medication adherence.