What is the usual starting and maintenance dose of donepezil for adults with Alzheimer disease?

Normal Dose of Donepezil

Start donepezil at 5 mg once daily in the evening, just prior to retiring, and increase to 10 mg once daily after 4–6 weeks if well tolerated. 1, 2, 3

Starting Dose

• Begin with 5 mg once daily taken in the evening before bedtime for all patients with mild to moderate Alzheimer's disease 1, 3
• Take with food to minimize gastrointestinal side effects such as nausea, vomiting, and diarrhea 1, 2
• The 5 mg starting dose allows assessment of tolerability before escalation 3

Maintenance Dose

• Increase to 10 mg once daily after 4–6 weeks if the 5 mg dose is well tolerated 1, 2, 3
• The 10 mg dose provides superior cognitive and functional benefits compared to 5 mg 1
• Do not increase to 10 mg before completing at least 4 weeks at the 5 mg dose 3

Higher Dose for Moderate to Severe Disease

• For patients with moderate to severe Alzheimer's disease who have been stable on 10 mg daily for at least 3 months, a 23 mg once-daily dose may be considered 3
• The 23 mg tablet must be swallowed whole and cannot be split, crushed, or chewed 3
• The 23 mg dose has markedly higher rates of nausea (11.8%) compared to continuing 10 mg (3%) 3

Timing and Administration

• Administer in the evening, just prior to retiring, as this timing reduces sleep disturbances 1, 3
• Can be taken with or without food, though taking with meals reduces gastrointestinal adverse effects 1, 2
• Once-daily dosing is appropriate due to donepezil's 70-hour half-life 1

Dose-Related Side Effects

• The 10 mg dose carries higher risk of cholinergic side effects compared to 5 mg: nausea/vomiting (relative risk 2.54), diarrhea (relative risk 2.57), and anorexia (relative risk 3.21) 1, 4
• Gradual titration over 4–6 weeks minimizes these side effects 1, 2
• Initial agitation may occur but typically resolves within a few weeks 2, 4

Special Populations

• No dose adjustment is needed for hepatic impairment, as donepezil is not hepatotoxic 2
• For severe renal impairment (creatinine clearance ≈30 mL/min), standard dosing of donepezil remains appropriate 5

Common Pitfalls to Avoid

• Do not prescribe donepezil for mild cognitive impairment, as evidence shows no significant benefit in this population 1, 4
• Do not escalate to 10 mg before 4 weeks at 5 mg, as premature dose increases worsen tolerability 3
• Do not administer in the morning, as this increases sleep disturbances 1
• Do not expect dramatic improvement; donepezil produces statistically significant but modest cognitive benefits, with approximately 20–35% of patients achieving clinically meaningful improvement 2

Assessment Timeline

• Clinical benefit typically becomes apparent within 3 months of starting therapy 2
• A full efficacy evaluation requires 6–12 months of continuous treatment using caregiver reports, functional assessments, and cognitive testing 2, 4
• Brief mental status tests (e.g., MMSE) are relatively insensitive to donepezil effects and should not be the sole measure of response 2