Aricept Starting Dose
Start Aricept (donepezil) at 5 mg once daily in the evening, just prior to retiring. 1
Initial Dosing Protocol
The FDA-approved starting dose is 5 mg once daily for all patients with Alzheimer's disease, regardless of severity (mild, moderate, or severe). 1
Administer in the evening at bedtime to minimize sleep disturbances and optimize tolerability. 2, 3, 1
The medication can be taken with or without food, though taking it with food may help minimize gastrointestinal side effects during dose escalation. 2, 1
Dose Escalation Timeline
Increase to 10 mg once daily after 4-6 weeks if the initial 5 mg dose is well tolerated. 2, 3, 1
Do not advance to 10 mg before 4 weeks have elapsed on the 5 mg dose, as this increases the risk of cholinergic side effects. 1
The 4-6 week waiting period allows assessment of tolerability and minimizes gastrointestinal adverse effects (nausea, vomiting, diarrhea), which are significantly more common with premature dose escalation. 3, 1
Rationale for Conservative Starting Dose
The 5 mg starting dose is based on the pharmacokinetic profile of donepezil, which has a 70-hour half-life requiring approximately 2-3 weeks to reach steady-state plasma concentrations. 4, 5 Starting at 5 mg and waiting 4-6 weeks before escalation significantly reduces the relative risk of:
- Nausea/vomiting (RR 2.54 at 10 mg vs 5 mg) 3
- Diarrhea (RR 2.57 at 10 mg vs 5 mg) 3
- Anorexia (RR 3.21 at 10 mg vs 5 mg) 3
Common Pitfalls to Avoid
Do not start at 10 mg, even in patients with more advanced disease, as this dramatically increases discontinuation rates due to adverse effects. 1
Do not split, crush, or chew tablets (particularly important for higher-dose formulations). 1
70-80% of gastrointestinal adverse effects occur within the first 2 weeks, and 60-65% resolve within the first month, so counsel patients to continue therapy through this initial period. 6
Avoid twice-daily dosing—donepezil is designed for once-daily administration due to its long half-life. 6, 4