Donepezil

Antidementia Drug

Drug class: Acetylcholinesterase Inhibitor

Donepezil (ARICEPT)（中文：多奈哌齊）

Common Strengths

Donepezil is available in the following strengths:

• Tablets: 5mg, 10 mg
• Orally Disintegrating Tablets (ODT): 5 mg, 10 mg

Drug Trade Names

• Aricept

Drug Usage

Donepezil is indicated for:

• Treatment of mild, moderate, and severe dementia due to Alzheimer's disease.
• Off-label uses may include vascular dementia and dementia related to Parkinson's disease.

Mechanism of Action

Donepezil works by inhibiting the enzyme acetylcholinesterase. This inhibitor prevents the breakdown of acetylcholine, thereby increasing the concentration of acetylcholine in the brain, which is crucial for memory and cognitive functions.

Route of Administration

Donepezil can be administered orally as tablets or orally disintegrating tablets

Dosages

• Initial: 5 mg once daily at bedtime.
• Maintenance: May increase to 10 mg after 4-6 weeks.

Side Effects

Frequency	Adverse reactions
Common Side Effects	Nausea
	Diarrhea
	Insomnia
	Loss of appetite
Serious Side Effects	Bradycardia (slow heart rate)
	Gastrointestinal Bleeding
	Seizures
	Severe allergic reactions (e.g. difficulty breathing)

Pharmacokinetics

Donepezil has a half-life of approximately 70 hours, allowing for once-daily dosing. The onset of action typically occurs within a few weeks, with maximum effects seen after several months of treatment.

Drug Precautions

Pregnancy

There is little information available about the effects of donepezil on pregnancy and fetal development. As a result, healthcare providers typically advise against its use unless necessary.

Breastfeeding

Donepezil is excreted in breast milk; caution should be exercised when administered to nursing mothers.

Children and Elderly

Safety and efficacy have not been established in children. In elderly patients, monitoring for side effects is crucial due to increased sensitivity.

Drug Monitoring Items

Regular monitoring should include:

• Heart rate and rhythm (due to bradycardia risk)
• Gastrointestinal symptoms (to detect potential bleeding)
• Cognitive function assessments to evaluate efficacy

Drug Interactions

Donepezil may interact with various medications, particularly those affecting heart rhythm or gastrointestinal function. Notable interactions include:

• Anticholinergic Medications:
  • Anticholinergics (e.g. antihistamines, medications for overactive bladder) may diminish the effects of donepezil, potentially worsening symptoms of Alzheimer's disease due to their opposing mechanisms.
• Cholinergic Agents:
  • Combining donepezil with other cholinesterase inhibitor (like neostigmine) can lead to synergistic effects, increasing the risk of cholinergic side effects.
• Beta-Blockers:
  • Drugs such as metoprolol and carvedilol may increase the risk of bradycardia when taken with donepezil. Patients should be monitored for heart rate changes.
• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs):
  • The concurrent use of NSAIDs (e.g. ibuprofen, naproxen) may increase the risk of gastrointestinal bleeding and ulcers, especially in patients with a history of such conditions.
• CYP450 Enzyme Interactions:
  • Donepezil is metabolized by CYP3A4 and to a lesser extent CYP2D6.
  • Inhibitors of these enzymes (like ketoconazole and fluoxetine) can increase donepezil levels in the body, while inducers (such as rifampicin and phenytoin) may reduce its effectiveness by increasing its clearance.

FAQ

How Should I Take the Tablet?

Take donepezil once daily at bedtime, with or without food.

What Should I Avoid While Taking?

Avoid other medications that may affect heart rate or gastrointestinal function without consulting a healthcare provider.

What Happens if I Miss a Dose?

If you miss a dose, take it as soon as you remember on the same day; if it is close to the next dose, skip the missed dose and return to your regular schedule.