Is there a reason to take donepezil (Aricept) at night versus in the morning?

From the Guidelines

Donepezil should be taken at night rather than in the morning to minimize the impact of its side effects, such as nausea, vomiting, and diarrhea, which are reduced when the medication is taken with food and can be slept through when taken at bedtime. This approach is based on the medication's profile, as described in guidelines for managing Alzheimer's disease 1. When considering the administration of donepezil, it's crucial to weigh the potential benefits against the possible side effects.

Key Considerations

• Donepezil is given once daily, with a recommended starting dosage of 5 mg per day, which can be increased to 10 mg per day after four weeks, as outlined in the guidelines for managing Alzheimer's disease 1.
• The medication's side effects, such as nausea, vomiting, and diarrhea, are mild and can be reduced by taking it with food, but taking it at night allows patients to sleep through the initial onset of these side effects.
• The long half-life of donepezil, approximately 70 hours, ensures its effectiveness throughout the 24-hour period, regardless of the timing of administration.
• Consistency in taking the medication at the same time each day is essential to maintain steady blood levels and optimize its therapeutic effects.

Administration Timing

• While nighttime administration is preferred to minimize side effects, morning dosing is a viable alternative if nighttime administration causes sleep disturbances or vivid dreams.
• It's essential to follow the healthcare provider's specific instructions regarding the timing of donepezil administration, as individual factors may influence the optimal dosing schedule.

From the FDA Drug Label

1. 1 Dosing in Mild to Moderate Alzheimer's Disease The recommended starting dosage of donepezil hydrochloride tablets is 5 mg administered once per day in the evening, just prior to retiring.
2. 2 Dosing in Moderate to Severe Alzheimer's Disease The recommended starting dosage of donepezil hydrochloride tablets is 5 mg administered once per day in the evening, just prior to retiring.
3. 3 Administration Information Donepezil hydrochloride tablets should be taken in the evening, just prior to retiring.

The reason to take donepezil at night versus the morning is that the drug label explicitly recommends administering the drug in the evening, just prior to retiring 2. This is stated for both mild to moderate and moderate to severe Alzheimer's disease. The exact reason for this recommendation is not provided in the label, but it suggests that taking the drug at night is the preferred administration schedule.

From the Research

Donepezil Administration Timing

• The timing of donepezil administration is recommended to be at bedtime due to its long elimination half-life of 70 hours 3.
• This recommendation is based on the drug's pharmacokinetics, which allows for once-daily dosing.
• There is no evidence to suggest that taking donepezil in the morning has any significant benefits or drawbacks compared to taking it at night.

Rationale for Bedtime Administration

• The long elimination half-life of donepezil allows for a single bedtime dose to maintain therapeutic levels throughout the day 3.
• Administering the drug at bedtime may help minimize potential side effects, such as nausea, vomiting, and diarrhea, which are commonly reported with donepezil use 4, 5.
• However, the incidence of these side effects can be minimized by increasing the dose after a longer period, such as 6 weeks 4.

Clinical Considerations

• Donepezil is generally well-tolerated, with most adverse events being mild and transient 4, 3.
• The drug has been extensively studied and is considered a first-line treatment for patients with mild to moderate Alzheimer's disease 4, 6.
• Long-term use of donepezil has been found to delay nursing-home placement and result in caregiver respite, and it slows deterioration of cognition and global function in patients with moderate-to-severe AD 3, 6.