Home > Medical Reference > Complementary Medicine

Donepezil


Pronunciation

 (doh NEP e zil)


U.S. Brand Names

 Aricept®


Synonyms

 E2020


Generic Available

 No


Canadian Brand Names

 Aricept®


Use

 Treatment of mild to moderate dementia of the Alzheimer's type


Use - Unlabeled/Investigational

 Attention-deficit/hyperactivity disorder (ADHD), behavioral syndromes in dementia


Pregnancy Risk Factor

 C


Pregnancy Implications

 Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women.


Lactation

 Excretion in breast milk unknown/not recommended


Contraindications

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


Warnings/Precautions

 Cholinesterase inhibitors may have vagotonic effects. May cause bradycardia and/or heart block with or without a history of cardiac disease; syncopal episodes have been associated with donepezil. Use with caution in patients with sick sinus syndrome or other supraventricular cardiac conduction abnormalities, in patients with seizures, COPD, or asthma; avoid use in nursing mothers. Use with caution in patients at risk of ulcer disease (ie, previous history or NSAID use), or in patients with bladder outlet obstruction. May cause diarrhea, nausea, and/or vomiting, which may be dose-related.


Adverse Reactions

>10%:

Central nervous system: Headache

Gastrointestinal: Nausea, diarrhea

1% to 10%:

Cardiovascular: Syncope, chest pain, hyper-/hypotension, atrial fibrillation, hot flashes

Central nervous system: Abnormal dreams, depression, dizziness, fatigue, insomnia, somnolence

Dermatologic: Bruising

Gastrointestinal: Anorexia, vomiting, weight loss, fecal incontinence, GI bleeding, bloating, epigastric pain

Genitourinary: Frequent urination

Neuromuscular & skeletal: Muscle cramps, arthritis, body pain

<1%: CHF, delusions, dysarthria, dysphasia, dyspnea, eosinophilia, intracranial hemorrhage, paresthesia, pruritus, thrombocytopenia, tremor

Postmarketing and/or case reports: Abdominal pain, agitation, cholecystitis, confusion, convulsions, hallucinations, heart block, hemolytic anemia, hyponatremia, neuroleptic malignant syndrome, pancreatitis, rash


Overdosage/Toxicology

 Implement general supportive measures. Donepezil can cause a cholinergic crisis characterized by severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increased muscle weakness is a possibility and may result in death if respiratory muscles are involved.

Tertiary anticholinergics, such as atropine, may be used as an antidote for overdose. I.V. atropine sulfate titrated to effect is recommended with an initial dose of 1-2 mg I.V., with subsequent doses based upon clinical response. Atypical increases in blood pressure and heart rate have been reported with other cholinomimetics when coadministered with quaternary anticholinergics such as glycopyrrolate.


Drug Interactions

 Substrate (minor) of CYP2D6, 3A4

Anticholinergic agents: Effects of donepezil may be inhibited by anticholinergic agents (benztropine)

Cholinergic agents: A synergistic effect may be seen with concurrent administration of succinylcholine or cholinergic agonists (bethanechol); excessive cholinergic stimulation and toxicity may occur; use caution


Ethanol/Nutrition/Herb Interactions

 Herb/Nutraceutical: St John's wort may decrease donepezil levels.


Mechanism of Action

 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 central nervous system.


Pharmacodynamics/Kinetics

Absorption: Well absorbed

Protein binding: 96%, primarily to albumin (75%) and 1-acid glycoprotein (21%)

Metabolism: Extensively to four major metabolites (two are active) via CYP2D6 and 3A4; undergoes glucuronidation

Bioavailability: 100%

Half-life elimination: 70 hours; time to steady-state: 15 days

Time to peak, plasma: 3-4 hours

Excretion: Urine (as unchanged drug)


Dosage

 Oral:

Children: ADHD (unlabeled use): 5 mg/day

Adults: Dementia of Alzheimer's type: Initial: 5 mg/day at bedtime; may increase to 10 mg/day at bedtime after 4-6 weeks


Monitoring Parameters

 Behavior, mood, bowel function


Patient Education

 This medication will not cure the disease, but may help reduce symptoms. Use as directed; do not increase dose or discontinue without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. May cause dizziness, sedation, or hypotension (rise slowly from sitting or lying position and use caution when driving or climbing stairs); vomiting or loss of appetite (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); or diarrhea (boiled milk, yogurt, or buttermilk may help). Report persistent abdominal discomfort; significantly increased salivation, sweating, tearing, or urination; flushed skin; chest pain or palpitations; acute headache; unresolved diarrhea; excessive fatigue, insomnia, dizziness, or depression; increased muscle, joint, or body pain; vision changes or blurred vision; or shortness of breath or wheezing. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.


Additional Information

 Donepezil does not significantly elevate liver enzymes.


Dental Health: Effects on Dental Treatment

 No significant effects or complications reported


Dental Health: Vasoconstrictor/Local Anesthetic Precautions

 No information available to require special precautions


Mental Health: Child/Adolescent Considerations

 Five children (8-17 years of age) with ADHD showed improvement when treated with donepezil (Wilens, 2000). Four of 8 patients with autism (mean age: 11 years of age; range: 7-19 years) showed significant improvement in behaviors in a retrospective pilot study (Hardan, 2002).

Hardan AY and Handen BL, "A Retrospective Open Trial of Adjunctive Donepezil in Children and Adolescents With Autistic Disorder," J Child Adolesc Psychopharmacol , 2002, 12(3): 237-41.

Wilens TE, Biederman J, Wong J, et al, "Adjunctive Donepezil in Attention Deficit Hyperactivity Disorder Youth: Case Series," J Child Adolesc Psychopharmacol , 2000, 10(3):217-22.


Dosage Forms

 Tablet, as hydrochloride: 5 mg, 10 mg


References

Hardan AY and Handen BL, "A Retrospective Open Trial of Adjunctive Donepezil in Children and Adolescents With Autistic Disorder," J Child Adolesc Psychopharmacol , 2002, 12(3):237-41.

Hoopes SP, "Donepezil for Tourette's Disorder and ADHD," J Clin Psychopharmacol , 1999, 19(4):381-2.

Rogers SL and Friedhoff LT, "The Efficacy and Safety of Donepezil in Patients With Alzheimer's Disease: Results of a U.S. Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial," Dementia , 1996, 7(6):293-303.

Wilens TE, Biederman J, Wong J, et al, "Adjunctive Donepezil in Attention Deficit Hyperactivity Disorder Youth: Case Series," J Child Adolesc Psychopharmacol , 2000, 10(3):217-22.


International Brand Names

 Aricept® (AT, AU, BE, CA, CH, CY, CZ, DE, DK, EG, ES, FI, FR, GB, HR, HU, ID, IE, IL, IT, JO, JP, KW, LB, NO, NZ, PL, PT, RO, RU, SE, SG, SI, TH, TR, YU, ZA); Asenta® (IL); Cristaclar® (AR); Eranz® (AR, CL, CO, CR, GT, HN, MX, PA, SV); Memac® (IT); Memorit® (IL); Yasnal® (PL)


A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is the first of its kind, requiring compliance with 53 standards of quality and accountability, verified by independent audit. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial process . A.D.A.M. is also a founding member of Hi-Ethics (www.hiethics.com) and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2007 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.
adam.com