What is the recommended dosing regimen for Aricep (donepezil) in a geriatric patient with Alzheimer's disease?

Donepezil (Aricept) Dosing for Geriatric Patients with Alzheimer's Disease

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

Initial Dosing Strategy

• Begin with 5 mg once daily in the evening for all patients with mild to moderate Alzheimer's disease, regardless of age 1, 2, 4
• Take the medication just prior to retiring to minimize sleep disturbances 3, 4
• Donepezil can be taken with or without food, though taking it with food reduces gastrointestinal side effects 1, 4

Dose Escalation Timeline

• Wait 4-6 weeks before increasing to 10 mg daily to allow tolerance to develop and minimize cholinergic side effects 1, 2, 3, 4
• The 10 mg dose provides superior cognitive and functional benefits compared to 5 mg, with improvements maintained for 21-81 weeks 3, 5
• Do not escalate to 10 mg sooner than 4 weeks, as premature dose increases significantly increase the risk of nausea (relative risk 2.54), vomiting, and diarrhea (relative risk 2.57) 3

Higher Dose Considerations 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, the FDA-approved maximum dose is 23 mg once daily 4
• If escalating to 23 mg, use intermediate dose titration (either 15 mg for 4 weeks or alternating 10 mg/23 mg for 4 weeks) before reaching the full 23 mg dose to reduce cholinergic adverse events, particularly nausea 6
• The 23 mg tablet should not be split, crushed, or chewed 4

Special Populations: Renal Impairment

• For patients with severe renal impairment (creatinine clearance approximately 30 mL/min), standard donepezil dosing (5-10 mg) does not require adjustment 1
• However, if combining with memantine in severe renal impairment, memantine dose reduction is necessary 1, 2

Monitoring and Assessment Period

• Allow 6-12 months to adequately assess treatment benefit before considering discontinuation 2
• Approximately 20-35% of patients will achieve clinically meaningful improvement (≥4 points on ADAS-cog or ≥3 points on MMSE), even though average improvements are modest 1, 3
• Use comprehensive assessments including caregiver reports and functional measures, as brief mental status tests are relatively insensitive to cholinesterase inhibitor effects 2

Managing Side Effects

• Most common adverse events are gastrointestinal: nausea, vomiting, diarrhea, and anorexia 1, 3, 4
• These effects are dose-dependent and occur more frequently with 10 mg than 5 mg 1
• Minimize side effects by: taking medication with food, using gradual dose titration over 4-6 weeks, and administering at bedtime 1, 2, 3
• Some patients may exhibit initial agitation, which typically subsides after the first few weeks 1
• Monitor for bradycardia and heart block, particularly in patients with underlying cardiac conduction abnormalities 4

Common Pitfalls to Avoid

• Do not escalate too quickly: The 7-day dose escalation used in early trials resulted in higher adverse event rates; the 4-6 week titration period significantly improves tolerability 1, 5
• Do not discontinue prematurely: Some patients require up to 12 months to demonstrate benefit 2
• Do not prescribe for mild cognitive impairment: Evidence shows no significant benefit in this population 3
• Address realistic expectations upfront: Donepezil provides modest symptomatic improvement and slows decline but does not reverse the disease process 1, 2

When to Consider Combination Therapy

• If the patient continues to decline after 3 months on donepezil 10 mg, add memantine (target dose 20 mg/day) while continuing donepezil 2
• Combination therapy is superior to switching cholinesterase inhibitors, as there is no convincing evidence that one agent is more effective than another 2