Is it okay to give Donepezil (Aricept) 10mg twice daily?

Donepezil 10 mg Twice Daily Is Not Recommended

Donepezil should not be administered at 10 mg twice daily as this exceeds the FDA-approved dosing and significantly increases the risk of adverse effects without proven additional benefits. 1, 2

Standard Dosing Recommendations

• Donepezil is typically prescribed at 5-10 mg once daily, with 10 mg/day being the maximum FDA-approved standard dose for mild to moderate Alzheimer's disease 1
• The medication is designed for once-daily administration, not twice daily dosing 3
• When prescribed, donepezil should be taken in the morning rather than at bedtime to minimize sleep disturbances 3

Pharmacokinetic Considerations

• Doubling the standard maximum dose to 10 mg twice daily (20 mg total) would significantly increase plasma concentrations and likely exceed the therapeutic window 4
• While a 23 mg sustained-release formulation exists, this is specifically designed with modified pharmacokinetics to maintain appropriate blood levels 4
• Standard immediate-release formulations given twice daily would create undesirable peak-trough fluctuations 4

Adverse Effects Risk

• Gastrointestinal side effects are dose-dependent, with higher incidence at 10 mg compared to 5 mg 2

• Common adverse effects include:

  • Nausea and vomiting (relative risk 2.54) 2
  • Diarrhea (relative risk 2.57) 2
  • Anorexia (relative risk 3.21) 2
  • Muscle cramps, particularly leg cramps 2
  • Dizziness (relative risk 1.47) 2

• Higher doses are associated with increased withdrawal rates from clinical studies due to adverse events 5, 6

Evidence on Higher Dosing

• While a small pilot study examined donepezil at doses up to 20 mg/day, this was not sufficient to establish safety and efficacy for routine clinical use 7
• The Cochrane review on donepezil found that "benefits on 23 mg/day were no greater than on 10 mg/day" and that adverse events increased with higher doses 5
• In clinical trials, withdrawal rates and adverse events were consistently higher with increased dosing 5, 6

Special Considerations for Elderly Patients

• In older adults with multimorbidity, medication simplification is recommended to improve adherence 3
• For patients with mild dementia, the American Geriatrics Society recommends taking donepezil in the morning rather than at bedtime to minimize sleep disturbances 3
• In patients with renal impairment, dose adjustment may be necessary, making twice-daily high-dose regimens particularly problematic 3

Alternative Approaches

• If treatment response is inadequate at 10 mg once daily:
  • Consider adding memantine (though evidence does not support its use in mild Alzheimer's disease) 3
  • Ensure the current 10 mg dose is taken consistently in the morning 3
  • Evaluate for other factors affecting cognition (sleep, other medications, comorbidities) 3

Clinical Recommendation

• Maintain the standard dosing of donepezil at 5-10 mg once daily 1, 5
• If the patient is currently on 10 mg at bedtime, consider switching to morning administration to improve sleep and potentially enhance effectiveness 3
• Monitor for adverse effects even at standard doses, particularly gastrointestinal symptoms 2
• For patients with mild to moderate Alzheimer's disease who need additional symptom management, consider other approved treatment options rather than exceeding the recommended donepezil dose 5