Donepezil

ATC code

N06DA02

Therapeutic class

Acetylcholinesterase inhibitor · Anti-dementia drug

Forms

oral tablet, orally disintegrating tablet, film-coated tablet

Brand names

Aricept (FR) · Aricept Flas (ES) · Donepezil Hydrochloride (US)

Overall confidence

high

Regulatory sources consulted

openfda-label-f8867ea9-a608-4b0f-9052-fa5c44d7e7c2
aemps-cima-ft-68214
ansm-bdpm-rcp-69972923
CredibleMeds.org
Flockhart Table
OpenFDA · N06DA02
RxNorm rxcui 135447 ↗

Approved indications

Treatment of dementia of the Alzheimer's type. Efficacy has been demonstrated in patients with mild, moderate, and severe Alzheimer's Disease.

Contraindications

Absolute

Known hypersensitivity to donepezil, piperidine derivatives, or any of the excipients.

Clinical warnings

Major warning · Vagotonic effects on heart rate (e.g., bradycardia, sinoatrial block, atrioventricular block). Risk of syncope. Cases of QTc prolongation and Torsades de Pointes have been reported. — ANSM SPC
Major warning · Risk of Neuroleptic Malignant Syndrome (NMS), a potentially life-threatening condition, especially in patients receiving concomitant antipsychotics. — ANSM SPC
Cholinomimetics may cause generalized convulsions, although seizures may also be a manifestation of Alzheimer's Disease. — ANSM SPC

Drug interactions

ModerateKetoconazoleJ02AB02
Mechanism: Inhibition of donepezil metabolism via CYP3A4, increasing its plasma concentrations (approx. 30%) and the risk of cholinergic adverse effects.
Recommendation: Monitor for cholinergic adverse effects (bradycardia, nausea). Consider a dose reduction of donepezil if necessary.
ANSM SPC
HighAmiodaroneC01BD01
Mechanism: Additive effect on QTc interval prolongation. Both drugs can prolong the QTc, significantly increasing the risk of serious ventricular arrhythmias such as Torsades de Pointes.
Recommendation: Combination is recommended to be avoided. If concomitant use is unavoidable, close clinical and electrocardiographic (ECG) monitoring is required.
ANSM SPC
ModerateOxybutyninG04BD04
Mechanism: Pharmacodynamic antagonism. Donepezil increases acetylcholine, while anticholinergic drugs like oxybutynin block its effects, potentially reducing the efficacy of both treatments.
Recommendation: Avoid concomitant use, as anticholinergics may interfere with the efficacy of cholinesterase inhibitors.
OpenFDA labelANSM SPC

Adverse events

Common (≥1%)

diarrhea · nausea · headache · muscle cramps · fatigue · insomnia · vomiting · anorexia · common cold

Rare but serious

rhabdomyolysis · neuroleptic malignant syndrome · hepatitis · gastrointestinal hemorrhage · seizures · heart block · QTc interval prolongation · Torsades de Pointes · syncope

Pregnancy and lactation

FDA category: Not Recommended

There are no adequate data in pregnant women. Animal studies showed increased stillbirths and decreased offspring survival. Use is not recommended during pregnancy.