Section 05 · Monograph
Donepezil
Reviewed Nov 2026FDA label
AriceptAChE inhibitor
- Forms
- Tab: 5, 10, 23mg | ODT: 5, 10mg
- Dose
- Start 5mg qHS, may increase to 10mg after 4-6wk
- MOA
- Inhibits acetylcholinesterase
Indications
- Treatment of dementia of the Alzheimer's type, mild to moderate severity (as monotherapy)FDA-labeled
- Treatment of dementia of the Alzheimer's type, moderate to severe severity (monotherapy or with memantine)FDA-labeled
Off-Label Uses
- Dementia with Lewy bodiesOff-label
- Parkinson's disease dementiaOff-label
- Vascular dementia / mixed dementiaOff-label
- Mild cognitive impairment (not FDA-approved; modest evidence)Off-label
Mechanism of Action
- Reversible, non-competitive inhibitor of acetylcholinesterase (AChE), increasing synaptic acetylcholine in cerebral cortex
- Highly selective for AChE over butyrylcholinesterase (BuChE), resulting in relatively fewer peripheral cholinergic effects
- Mechanism is symptomatic/palliative; does not alter the underlying neurodegenerative disease course
Full Dosing
Adult / usual
- Mild-to-moderate AD: initiate 5 mg PO once daily at bedtime
- May increase to 10 mg once daily after 4-6 weeks based on tolerability and clinical response
- Moderate-to-severe AD: after ≥3 months on 10 mg/day, may increase to 23 mg once daily
- 23 mg tablet must be swallowed whole (not split, crushed, or chewed)
- Orally disintegrating tablet (Aricept ODT) placed on tongue to dissolve, then followed with water
- If therapy is interrupted for an extended period, re-titrate from the starting dose
Renal
- No dosage adjustment required for renal impairment; use with caution in hepatic impairment
Contraindications
- Known hypersensitivity to donepezil hydrochloride
- Known hypersensitivity to piperidine derivatives
Drug Interactions
- CYP2D6 and CYP3A4 inhibitors (ketoconazole, quinidine, erythromycin) may increase donepezil plasma concentrations
- CYP450 inducers (rifampin, phenytoin, carbamazepine) may decrease donepezil levels and efficacy
- Anticholinergic drugs may antagonize donepezil's cholinergic effect
- Other cholinesterase inhibitors or cholinergic agonists produce synergistic cholinergic toxicity
- Succinylcholine: exaggerated muscle relaxation possible during anesthesia
- NSAIDs: increased risk of GI bleeding
- Beta-blockers and other bradycardia-inducing agents: additive risk of bradycardia/AV block
Adverse Effects
- Nausea, vomiting, and diarrhea (most common, dose-related)
- Insomnia and abnormal dreams
- Muscle cramps
- Fatigue and anorexia
- Dizziness and headache
- Bradycardia and syncope
- Weight loss, particularly at 23 mg dose
- Rare: seizures, GI bleeding, hepatotoxicity
Monitoring Parameters
- Baseline and periodic heart rate/rhythm; ECG in patients with conduction abnormalities
- Weight and nutritional status, especially at higher doses
- Signs/symptoms of active GI bleeding, particularly with concurrent NSAIDs
- Cognitive and functional status using standardized scales periodically
- Urinary symptoms suggestive of obstruction
- Signs of syncope or falls, especially early in treatment
Pregnancy & Lactation
- No adequate, well-controlled studies in pregnant women
- Animal reproduction studies showed developmental toxicity only at maternally toxic dose levels
- Use during pregnancy only if potential benefit justifies potential fetal risk
- Unknown whether excreted in human milk; caution advised if used in a nursing mother