Maximum Dose of Donepezil
The maximum recommended dose of donepezil is 23 mg per day for patients with moderate to severe Alzheimer's disease, while the maximum dose for mild to moderate disease is 10 mg per day. 1
Dosing Algorithm by Disease Severity
Mild to Moderate Alzheimer's Disease
- Start at 5 mg once daily in the evening, just prior to retiring 1, 2, 3
- Increase to 10 mg once daily after 4-6 weeks if well tolerated 1, 2, 4
- Maximum dose: 10 mg per day for this population 1, 2
Moderate to Severe Alzheimer's Disease
- Start at 5 mg once daily in the evening 1
- Escalate to 10 mg after 4-6 weeks if tolerated 1
- Further escalate to 23 mg per day only after at least 3 months on 10 mg 1
- Maximum dose: 23 mg per day 1
Critical Titration Considerations for 23 mg Dose
Dose titration before escalating to 23 mg significantly reduces cholinergic adverse events, particularly nausea. 5 The FDA label specifies that patients must be on 10 mg daily for at least 3 months before considering the 23 mg dose. 1
Two evidence-based titration strategies exist for escalating from 10 mg to 23 mg:
- 15 mg daily for 4 weeks before escalating to 23 mg (preferred method showing fewer adverse events) 5
- Alternating 10 mg and 23 mg daily for 4 weeks before full escalation 5
Direct escalation from 10 mg to 23 mg without intermediate titration results in significantly more nausea compared to gradual titration approaches. 5
Side Effect Profile by Dose
Gastrointestinal adverse events are dose-dependent and significantly more common at higher doses:
- Nausea incidence: 11.8% at 23 mg vs 3% at 10 mg 1
- Relative risk at 10 mg vs 5 mg: nausea/vomiting 2.54, diarrhea 2.57, anorexia 3.21 3
- These effects can be minimized by taking donepezil with food and using gradual titration 2, 3
Administration Details
- Take in the evening, just prior to retiring 1
- Can be taken with or without food 1
- The 23 mg tablet must not be split, crushed, or chewed 1
- Taking at bedtime rather than morning reduces sleep disturbances 3
Common Pitfall to Avoid
Do not escalate to 23 mg in patients with mild to moderate disease—the 23 mg dose is FDA-approved only for moderate to severe Alzheimer's disease and carries higher risk of adverse events without established benefit in milder disease. 1