Evigrade

Donepezil

AEMPS

Selective reversible acetylcholinesterase inhibitor

ATC code: N06DA02

Brand names: Aricept Evess, Aricept, Donaz

Updated · Methodology

Indications

A

Alzheimer disease

First line

First-line for mild-to-severe Alzheimer's disease ( NG97, 2018). Starting dose 5 mg once daily at bedtime; uptitrate to 10 mg after 4–6 weeks. For severe disease a 23 mg dose is available in the US, while the EU continues 10 mg. The 2018 Cochrane meta-analysis showed cognitive improvement (ADAS-Cog) by 2.9 points and functional gains. The effect is symptomatic and does not modify progression.

ICD-10: G30 · ICD-11: 8A20

B

Dementia

Second line

In dementia with Lewy bodies and Parkinson's disease dementia, acetylcholinesterase inhibitors (donepezil, rivastigmine) are used off-label per 2024 to ease cognitive symptoms and psychotic features. Among formally approved EU options for these diagnoses, rivastigmine is more commonly registered.

ICD-10: F03 · ICD-11: 6D8Z

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

F

Memory and concentration enhancement

Not recommended

Donepezil is a cholinesterase inhibitor. It is prescribed only for mild-to-moderate Alzheimer's disease ( 2018 and NG97 guidelines). In biohacker communities, donepezil is promoted as a cognitive enhancer for healthy students and knowledge workers. Clinical studies in healthy adults have not shown improvement in memory or attention. The drug carries serious risks: bradycardia, syncope, nausea, vomiting, diarrhea, weight loss, and seizures. In healthy people these risks are not justified. If donepezil was recommended for memory improvement in a healthy person, consider seeking a second opinion.

How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

A selective reversible acetylcholinesterase inhibitor in the CNS. In Alzheimer's disease, it raises synaptic acetylcholine, partly compensating cholinergic deficit. Does not affect peripheral butyrylcholinesterase, so causes fewer GI side effects than rivastigmine. CYP2D6- and CYP3A4-metabolized; half-life 70 hours – once-daily dosing.

Safety

Contraindications

  • Hypersensitivity to donepezil or piperidine derivatives
  • Pregnancy and lactation
  • Age under 18

Serious adverse effects

  • Bradycardia and AV block, syncope
  • QT prolongation and ventricular arrhythmias
  • GI bleeding (especially with NSAIDs)
  • Cholinergic crisis in overdose
  • Seizures

Common adverse effects

  • Nausea, vomiting, diarrhea
  • Reduced appetite and weight loss
  • Insomnia and vivid dreams
  • Headache
  • Bradycardia
  • Muscle cramps

Pregnancy: can you take Donepezil?

Not indicated – Alzheimer's in women of reproductive age is exceedingly rare.

Breastfeeding: can you take Donepezil?

No data. Not used during lactation.

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Take once daily at bedtime – vivid dreams and night agitation occur in some patients; switch to morning if so. Clinical effect becomes apparent at 6–12 weeks. Combination with memantine in moderate-to-severe disease augments effect (Tariot 2004). In patients with bradycardia, sick sinus syndrome, or AV conduction disturbances, bradycardia and syncope risk – obtain ECG before initiation.
Label mentions29 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

  • Moderateantipsicóticosclass named in the label
    «Síndrome neuroléptico maligno (SNM): Se han notificado casos de SNM, una patología que puede amenazar la vida, ocurre en muy raras ocasiones en asociación a donepezilo, particularmente en pacientes…»

    AEMPS, section 4.4 · Open on CIMA

  • «Ni donepezilo hidrocloruro ni ninguno de sus metabolitos inhiben el metabolismo de teofilina, warfarina, cimetidina o digoxina en seres humanos. La administración concomitante de digoxina o…»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateDigoxin
    «Ni donepezilo hidrocloruro ni ninguno de sus metabolitos inhiben el metabolismo de teofilina, warfarina, cimetidina o digoxina en seres humanos. La administración concomitante de digoxina o…»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateErythromycin
    «Ni donepezilo hidrocloruro ni ninguno de sus metabolitos inhiben el metabolismo de teofilina, warfarina, cimetidina o digoxina en seres humanos. La administración concomitante de digoxina o…»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateFluoxetine
    «Ni donepezilo hidrocloruro ni ninguno de sus metabolitos inhiben el metabolismo de teofilina, warfarina, cimetidina o digoxina en seres humanos. La administración concomitante de digoxina o…»

    AEMPS, section 4.5 · Open on CIMA

  • Moderateinhibidores del CYP2D6class named in the label
    «Ni donepezilo hidrocloruro ni ninguno de sus metabolitos inhiben el metabolismo de teofilina, warfarina, cimetidina o digoxina en seres humanos. La administración concomitante de digoxina o…»

    AEMPS, section 4.5 · Open on CIMA

  • Moderateinhibidores del CYP3A4class named in the label
    «Ni donepezilo hidrocloruro ni ninguno de sus metabolitos inhiben el metabolismo de teofilina, warfarina, cimetidina o digoxina en seres humanos. La administración concomitante de digoxina o…»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateItraconazole
    «Ni donepezilo hidrocloruro ni ninguno de sus metabolitos inhiben el metabolismo de teofilina, warfarina, cimetidina o digoxina en seres humanos. La administración concomitante de digoxina o…»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateKetoconazole
    «Ni donepezilo hidrocloruro ni ninguno de sus metabolitos inhiben el metabolismo de teofilina, warfarina, cimetidina o digoxina en seres humanos. La administración concomitante de digoxina o…»

    AEMPS, section 4.5 · Open on CIMA

  • Moderatemedicamentos que prolongan el QTclass named in the label
    «Se han notificado casos de prolongación del intervalo QTc y de torsade de pointes con donepezilo. Se recomienda precaución cuando se utilice donepezilo en combinación con otros medicamentos que se…»

    AEMPS, section 4.5 · Open on CIMA

  • ModeratePhenytoin
    «Ni donepezilo hidrocloruro ni ninguno de sus metabolitos inhiben el metabolismo de teofilina, warfarina, cimetidina o digoxina en seres humanos. La administración concomitante de digoxina o…»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateQuinidine
    «Ni donepezilo hidrocloruro ni ninguno de sus metabolitos inhiben el metabolismo de teofilina, warfarina, cimetidina o digoxina en seres humanos. La administración concomitante de digoxina o…»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateRifampicin
    «Ni donepezilo hidrocloruro ni ninguno de sus metabolitos inhiben el metabolismo de teofilina, warfarina, cimetidina o digoxina en seres humanos. La administración concomitante de digoxina o…»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateWarfarin
    «Ni donepezilo hidrocloruro ni ninguno de sus metabolitos inhiben el metabolismo de teofilina, warfarina, cimetidina o digoxina en seres humanos. La administración concomitante de digoxina o…»

    AEMPS, section 4.5 · Open on CIMA

  • «Antiarrítmicos de clase III (p. ej., amiodarona, sotalol)»

    AEMPS, section 4.5 · Open on CIMA

  • «Ciertos antidepresivos (p. ej., citalopram, escitalopram, amitriptilina)»

    AEMPS, section 4.5 · Open on CIMA

  • antiarrítmicosclass named in the label
    «Antiarrítmicos de clase IA (p. ej., quinidina)»

    AEMPS, section 4.5 · Open on CIMA

  • «Ciertos antidepresivos (p. ej., citalopram, escitalopram, amitriptilina)»

    AEMPS, section 4.5 · Open on CIMA

  • «Ciertos antibióticos (p. ej., claritromicina, eritromicina, levofloxacino, moxifloxacino)»

    AEMPS, section 4.5 · Open on CIMA

  • «Ciertos antidepresivos (p. ej., citalopram, escitalopram, amitriptilina)»

    AEMPS, section 4.5 · Open on CIMA

  • «Ciertos antibióticos (p. ej., claritromicina, eritromicina, levofloxacino, moxifloxacino)»

    AEMPS, section 4.5 · Open on CIMA

  • «Ciertos antibióticos (p. ej., claritromicina, eritromicina, levofloxacino, moxifloxacino)»

    AEMPS, section 4.5 · Open on CIMA

  • neuromuscular blockersclass named in the label
    «DRUG INTERACTIONS: A synergistic effect may be expected with concomitant administration of succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists (7.2)»

    FDA, section 7 · Open on DailyMed

  • «Otros antipsicóticos (p. ej., derivados de la fenotiazina, sertindol, pimozida, ziprasidona)»

    AEMPS, section 4.5 · Open on CIMA

  • «Antiarrítmicos de clase III (p. ej., amiodarona, sotalol)»

    AEMPS, section 4.5 · Open on CIMA

  • «Otros antipsicóticos (p. ej., derivados de la fenotiazina, sertindol, pimozida, ziprasidona)»

    AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

  • CriticalGalantamine
    «Debido a su mecanismo de acción, galantamina no se debe administrar concomitantemente con otros colinomiméticos (tales como ambenonio, donepezilo, neostigmina, piridostigmina, rivastigmina o…»

    AEMPS, section 4.5 · Open on CIMA

  • «En estudios farmacocinéticos (FC) a dosis únicas realizados en sujetos jóvenes sanos, no se han observado interacciones relevantes principio activo-principio activo entre memantina y…»

    AEMPS, section 4.5 · Open on CIMA

  • «Donepezilo y galantamina, ambos sustratos de CYP2D6 y CYP3A4 no tienen un efecto clínicamente relevante sobre la farmacocinética de la fracción antipsicótica activa.»

    AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Donepezil used for?

Donepezil is evaluated for the following indications with varying evidence strength: Alzheimer disease (evidence tier A), Dementia (evidence tier B), Memory and concentration enhancement (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Donepezil?

Common side effects of Donepezil (≥ 1 in 100): Nausea, vomiting, diarrhea, Reduced appetite and weight loss, Insomnia and vivid dreams, Headache, Bradycardia, Muscle cramps. See the Safety section for uncommon and serious reactions.

Is Donepezil safe during pregnancy?

Not indicated – Alzheimer's in women of reproductive age is exceedingly rare.

Is Donepezil compatible with breastfeeding?

No data. Not used during lactation.

Who should not take Donepezil?

Donepezil is contraindicated in: Hypersensitivity to donepezil or piperidine derivatives; Pregnancy and lactation; Age under 18. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

Other drugs in this group

Duloxetine, Escitalopram, Fluoxetine, Fluvoxamine, Hopantenic acid (calcium hopantenate), Paroxetine, Saffron (Crocus sativus stigma extract), Agomelatine