donepezil
cholinesterase inhibitor· Brands: Aricept, Aricept Evess, Donepezil Hydrochloride, AlzheimPO
Mechanism of action
Donepezil reversibly inhibits acetylcholinesterase, the enzyme that hydrolyses acetylcholine in the synaptic cleft. This enhances cholinergic neurotransmission, which is thought to improve cognitive function in patients with Alzheimer's disease by increasing acetylcholine availability at central synapses.
Pharmacokinetics
Donepezil is well absorbed after oral administration with a bioavailability of around 100%. It undergoes extensive first-pass metabolism, primarily by the cytochrome P450 enzymes CYP2D6 and CYP3A4. The half-life is approximately 70 hours, allowing for once-daily dosing. It is metabolised to active and inactive metabolites, with excreted mainly in the urine.
Indications & dosing
Alzheimer's disease (mild to moderate)
Start with 5 mg once daily for 4 weeks; increase to 10 mg once daily if tolerated.
- adult · PO: 5–10 mg once daily · Start with 5 mg once daily for 4 weeks; increase to 10 mg once daily if tolerated.
Alzheimer's disease (moderate to severe)
Start with 5 mg once daily; increase to 10 mg after 4 weeks; may increase to 23 mg after at least 3 months on 10 mg if tolerated.
- adult · PO: 5–23 mg once daily · Start with 5 mg once daily; increase to 10 mg after 4 weeks; may increase to 23 mg after at least 3 months on 10 mg if tolerated.
Contraindications & precautions
- Hypersensitivity to donepezil, piperidine derivatives, or any excipient · Do not use in patients with a history of allergic reaction to donepezil or related compounds.
- Sick sinus syndrome or other supraventricular conduction abnormalities (e.g., heart block) · Risk of bradycardia and heart block. Consider ECG monitoring before and during treatment.
- Active peptic ulcer disease · Donepezil increases gastric acid secretion, which may worsen ulceration or precipitate GI bleeding.
- Use with caution in patients with sick sinus syndrome or other supraventricular conduction abnormalities; monitor ECG and heart rate, especially when starting or increasing the dose.
- Use with caution in patients with active peptic ulcer disease or those taking NSAIDs, as donepezil increases gastric acid secretion and may cause GI bleeding.
- Use with caution in patients with epilepsy or a history of seizures, as donepezil may lower the seizure threshold.
- Monitor for weight loss in patients with low body weight, as anorexia and weight loss may occur.
Adverse effects
- Nausea
- Diarrhoea
- Muscle cramps
- Bradycardiaserious
- Syncopeserious
- Seizuresserious
Monitoring, pregnancy & toxicity
- Heart rate (pulse) · At baseline and periodically
- Gastrointestinal symptoms · During dose escalation
- Weight · Periodically
- Skin for rash · At onset or if new symptoms
- Pregnancy: Not recommended during pregnancy. Consider alternative therapies unless potential benefit justifies risk.
- Toxicity: Bradycardia and syncope · Monitor pulse; if severe, consider stopping drug or using atropine.
- Toxicity: GI symptoms (nausea, vomiting, diarrhoea, abdominal pain) · Supportive care; antiemetics if needed; dose reduction or discontinuation.
- Toxicity: Muscle weakness and cramps · Supportive care; check electrolytes; consider discontinuation.
- Toxicity: Cholinergic crisis (excess salivation, lacrimation, urination, defecation, GI distress, bradycardia) · Stop drug; administer atropine IV if severe; supportive measures.
Clinical notes
Donepezil is indicated for the symptomatic treatment of mild to moderate Alzheimer's disease, and sometimes for severe disease. It is usually started at 5 mg once daily at bedtime, increased to 10 mg after 4 to 6 weeks if tolerated. A 23 mg dose is available for moderate to severe disease. Common side effects include nausea, diarrhoea, insomnia, muscle cramps, fatigue, and bradycardia. It may interact with anticholinergic drugs and with agents that affect CYP2D6 or CYP3A4. Given its cholinergic effects, caution is needed in patients with bradycardia, sick sinus syndrome, or active peptic ulcer disease. Treatment should be reviewed regularly for continued benefit.
Log in to read the full donepezil monograph
A free account unlocks the complete drug reference, the interaction checker, prescription practice and every other learning tool.
BNF; local formulary