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Medically reviewed by Last updated on Jul 6, 2020.


(doh NEP e zil)

Index Terms

  • Donepezil HCl
  • E2020

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Aricept: 5 mg, 10 mg, 23 mg

Generic: 5 mg, 10 mg, 23 mg

Tablet Disintegrating, Oral, as hydrochloride:

Generic: 5 mg, 10 mg

Brand Names: U.S.

  • Aricept

Pharmacologic Category

  • Acetylcholinesterase Inhibitor (Central)


Alzheimer's disease is characterized by cholinergic deficiency in the cortex and basal forebrain, which contributes to cognitive deficits. Donepezil reversibly and noncompetitively inhibits centrally active acetylcholinesterase, the enzyme responsible for hydrolysis of acetylcholine. This appears to result in increased concentrations of acetylcholine available for synaptic transmission in the CNS.


Well absorbed


Vdss: 12 to 16 L/kg


Extensive hepatic metabolism via CYP2D6 and 3A4 and glucuronidation to four major metabolites (two are active)


Urine (57%; 17% as unchanged drug); feces (15%)

Time to Peak

Plasma: Tablet, 10 mg: 3 hours; Tablet, 23 mg: ~8 hours; Note: Peak plasma concentrations almost twofold higher for the 23 mg tablet compared to the 10 mg tablet

Half-Life Elimination

70 hours; time to steady-state: 15 days

Protein Binding

~96%, primarily to albumin (75%) and alpha1-acid glycoprotein (21%)

Special Populations: Hepatic Function Impairment

Clearance decreased 20% in patients with stable alcoholic cirrhosis.

Special Populations: Elderly

Clearance decreases with increasing age. When compared with patients 65 years of age, 90-year-old patients have a 17% decrease in clearance, while 40-year-old patients have a 33% increase in clearance; effect may not be clinically significant.

Special Populations Note

Body weight: For body weight from 50 to 110 kg, clearance increased from 7.77 to 14.04 L/hour, with a value of 10 L/hour for 70 kg individuals.

CYP2D6 genotype: When compared with CYP2D6 extensive metabolizers, poor metabolizers had a 31.5% slower clearance and ultra-rapid metabolizers had a 24% faster clearance.

Use: Labeled Indications

Alzheimer disease: Treatment of mild, moderate, or severe dementia of the Alzheimer type.

Off Label Uses

Dementia (ie, Parkinson disease–related dementia, Lewy body dementia, vascular dementia)

Data from a multinational, randomized, double-blind, placebo-controlled trial support the use of donepezil in the treatment of dementia associated with Parkinson disease [Dubois 2012]. Data from 2 randomized, double-blind, placebo-controlled studies and an open-label extension study in Japanese patients support the use of donepezil for improving cognition in the treatment of Lewy body dementia [Ikeda 2013], [Ikeda 2015], [Mori 2012]. Data from a meta-analysis suggest that donepezil may be beneficial for the treatment of cognitive symptoms of vascular dementia; however, clinical effects were modest [Chen 2016].

Based on the American Psychiatric Association guidelines for the treatment of Alzheimer disease and other dementias, cholinesterase inhibitors may be used for patients with mild to moderate dementia associated with Parkinson disease. Additionally, these guidelines state that cholinesterase inhibitors can be considered for Lewy body dementia, with dosing and titration similar to those for patients with Alzheimer disease [APA [Rabins 2007]]. Based on the National Institute for Health and Care Excellence (NICE) guideline on management of dementia, donepezil is recommended for mild, moderate, and severe dementia with Lewy bodies [NICE 2018]. Based on the British Association for Psychopharmacology guidelines for clinical practice with anti-dementia drugs, cholinesterase inhibitors, including donepezil, are not recommended for patients with vascular dementia; however, those with mixed vascular dementia and Alzheimer disease may benefit [BAP [O'Brien 2017]]. According to the NICE guidelines, acetylcholinesterase inhibitors, such as donepezil, are only recommended for vascular dementia in cases of comorbid Alzheimer disease, Parkinson disease, or dementia with Lewy bodies [NICE 2018].


Hypersensitivity to donepezil, piperidine derivatives, or any component of the formulation

Documentation of allergenic cross-reactivity for drugs in this class is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Alzheimer disease: Oral:

Mild to moderate: Initial: 5 mg once daily; may increase to 10 mg once daily after 4 to 6 weeks (Birks 2018; Burns 1999; Homma 2000).

Moderate to severe: Initial: 5 mg once daily; may increase to 10 mg once daily after 4 to 6 weeks; may increase further to 23 mg once daily if stable on 10 mg daily for ≥3 months (Birks 2018; Farlow 2010; Homma 2016).

Note: Doses of 23 mg/day may be associated with a limited increase in efficacy compared to 10 mg/day and with increased adverse effects (Birks 2018; Farlow 2010).

Dementia (ie, Parkinson disease–related dementia, Lewy body dementia, vascular dementia) (off-label use): Oral: Initial: 5 mg once daily; may increase to 10 mg once daily after 4 to 6 weeks (APA [Rabins 2007]; Chen 2016; Wang 2015).

Discontinuation of therapy: Discontinuation of therapy may result in worsening of cognitive function (Howard 2012). Avoid abrupt discontinuation except in the case of severe adverse drug reaction to minimize withdrawal symptoms (eg, altered mental status, hallucinations, delusions, insomnia, increased anxiety and agitation). In general, cholinesterase inhibitors should be tapered using a 50% dose reduction or stepwise reduction via available dose formulations every 4 weeks to the lowest dose prior to discontinuation. Consider re-initiation if clear worsening of the condition occurs after withdrawal (Howard 2015; Reeve 2019).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing. Note: The Canadian labeling recommends a maximum dose of 5 mg once daily in elderly women (≥85 years of age) of low body weight.


Oral: Administer at bedtime without regard to food.

Aricept 23 mg tablet: Swallow whole with water; do NOT crush or chew due to an increased rate of absorption. The 23 mg strength is provided in a unique film-coated formulation different from the 5 mg or 10 mg tablet strengths, which results in an altered pharmacokinetic profile.

Aricept ODT: Allow tablet to dissolve completely on tongue and follow with water.


Store at 15°C to 30°C (59°F to 86°F).

Drug Interactions

Amifampridine: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Amifampridine. Amifampridine side effects may also be increased. Amifampridine may enhance the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase inhibitor side effects may also be increased. Monitor therapy

Anticholinergic Agents: Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Antipsychotic Agents: Acetylcholinesterase Inhibitors (Central) may enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. Monitor therapy

Benoxinate: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Benoxinate. Specifically, the effects of benoxinate may be prolonged. Monitor therapy

Beta-Blockers: Acetylcholinesterase Inhibitors may enhance the bradycardic effect of Beta-Blockers. Monitor therapy

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Monitor therapy

Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Consider therapy modification

Cholinergic Agonists: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Cholinergic Agonists. Specifically, cholinergic effects may be enhanced or increased. Monitor therapy

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Monitor therapy

Dipyridamole: May diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Fexinidazole [INT]: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole [INT]. Avoid combination

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Monitor therapy

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Monitor therapy

Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Acetylcholinesterase Inhibitors may diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Monitor therapy

Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Consider therapy modification

Succinylcholine: Acetylcholinesterase Inhibitors may increase the serum concentration of Succinylcholine. Management: Consider alternatives to this combination due to a risk of prolonged neuromuscular blockade. Consider therapy modification

Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.


Gastrointestinal: Diarrhea (5% to 15%), nausea (3% to 19%)

Nervous system: Insomnia (2% to 14%)

Miscellaneous: Accidental injury (7% to 13%)

1% to 10%:

Cardiovascular: Chest pain (2%), hypertension (3%), syncope (2% [placebo: 1%])

Dermatologic: Ecchymosis (4% to 5%), eczema (3%)

Endocrine & metabolic: Hyperlipidemia (2%), weight loss (3% to 5% [placebo: 1%])

Gastrointestinal: Anorexia (2% to 8% [placebo: 2% to 4%]), gastrointestinal hemorrhage (1%), vomiting (3% to 9%)

Genitourinary: Urinary frequency (2%), urinary incontinence (1% to 3%)

Hematologic & oncologic: Bruise (2%), hemorrhage (2%)

Nervous system: Abnormal dreams (3%), confusion (2%), depression (2% to 3%), dizziness (2% to 8%), drowsiness (1% to 2%), emotional lability (2%), fatigue (1% to 8%), hallucination (3% [placebo: 1%]), headache (3% to 10%), hostility (3%), nervousness (3%), pain (3% to 9%), personality disorder (2%)

Neuromuscular & skeletal: Arthritis (2%), asthenia (1% to 2%), back pain (3%), increased creatine phosphokinase in blood specimen (3%), muscle cramps (3% to 8%)

Miscellaneous: Fever (2%)

<1%: Gastrointestinal: Peptic ulcer


Cardiovascular: Heart block, prolonged QT interval on ECG (Leitch 2007; Tanaka 2009), torsades de pointes (Tanaka 2009)

Dermatologic: Skin rash (Lim 2018)

Endocrine & metabolic: Hyponatremia (Shareef 2017)

Gastrointestinal: Abdominal pain, cholecystitis, pancreatitis (Niinomi 2019)

Hematologic & oncologic: Hemolytic anemia

Hepatic: Hepatitis (Dierckx 2008; Verrico 2000)

Nervous system: Aggressive behavior, agitation (Leung 2014), neuroleptic malignant syndrome (Matsumoto 2004; Warwick 2008), seizure (Babic 1999; Kumlien 2010)

Neuromuscular & skeletal: Rhabdomyolysis (Fleet 2019; Sahin 2014)


Concerns related to adverse effects:

• Altered cardiac conduction: Donepezil may be associated with QT prolongation and torsades de pointes; use with caution in patients at risk of prolonged cardiac repolarization (Howes 2014). Cholinesterase inhibitors may have vagotonic effects which may cause bradycardia and/or heart block in patients with or without a history of cardiac disease; syncopal episodes have been associated with donepezil. Use with caution in patients with sick-sinus syndrome, bradycardia, or conduction abnormalities. Alzheimer treatment guidelines consider bradycardia to be a relative contraindication for use of centrally active cholinesterase inhibitors (APA [Rabins 2007]).

• Anorexia/weight loss: May cause anorexia and/or weight loss (dose-related).

• GI effects: May cause dose-related diarrhea, nausea, and/or vomiting; usually resolves in 1 to 3 weeks.

• Neuroleptic malignant syndrome: Rare cases of neuroleptic malignant syndrome (NMS) have been reported (Matsumoto 2004; Warwick 2008). Discontinuation of donepezil therapy may be necessary in patients presenting with symptoms of NMS (eg, hyperthermia, irregular pulse or blood pressure, cardiac arrhythmia, diaphoresis, muscle rigidity, mental status changes, elevated creatine phosphokinase [CPK], or unexplained high fever without additional symptoms).

• Rhabdomyolysis: Rare cases of rhabdomyolysis (including acute renal failure) have been reported after a few months of therapy (Sahin 2014) or in the days following therapy initiation and dose increase (Aricept Canadian product monograph 2014). Use with caution in patients with risk factors for rhabdomyolysis (eg, concomitant medications associated with rhabdomyolysis, history of muscular disorders, uncontrolled hypothyroidism, renal/hepatic impairment). Discontinuation of therapy may be necessary for marked elevation of CPK levels and/or symptoms (eg, muscle pain, tenderness or weakness, malaise, fever, dark urine) suggesting rhabdomyolysis.

Disease-related concerns:

• Peptic ulcer disease: Use with caution in patients at risk of ulcer disease (eg, previous history or NSAID use); cholinesterase inhibitors may increase gastric acid secretion. Monitor for symptoms of bleeding.

• Respiratory disease: Use with caution in patients with COPD and/or asthma.

• Seizure disorder: Use with caution in patients with a history of seizure disorder; cholinomimetics may potentially cause generalized seizures, although seizure activity may also result from Alzheimer disease.

• Urinary tract obstruction: Use with caution in patients with bladder outlet obstruction or prostatic hyperplasia; cholinomimetics may cause or worsen outflow obstructions, including possible exacerbation of BPH symptoms (APA [Rabins 2007]).

Special populations:

• Low-weight patients: Patients weighing <55 kg may experience more nausea, vomiting, and weight loss than patients ≥55 kg.

Dosage form specific issues:

• Aspartame: Some products may contain aspartame, which is metabolized to phenylalanine and must be avoided (or used with caution) in patients with phenylketonuria.

Monitoring Parameters

Mental status, weight, symptoms of GI intolerance, symptoms of active or occult GI bleeding.

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies.

Patient Education

What is this drug used for?

• It is used to treat dementia in people with Alzheimer's disease.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Diarrhea

• Nausea

• Vomiting

• Trouble sleeping

• Fatigue

• Loss of strength and energy

• Muscle cramps

• Lack of appetite

• Weight loss

• Headache

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Severe dizziness

• Passing out

• Slow heartbeat

• Abnormal heartbeat

• Trouble urinating

• Seizures

• Heartburn

• Severe abdominal pain

• Vomiting blood

• Black, tarry, or bloody stools

• Trouble breathing

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.