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Pronunciation(doh NEP e zil)
U.S. Brand NamesAricept®
SynonymsE2020
Generic AvailableNo
Canadian Brand NamesAricept®
UseTreatment of mild to moderate dementia of the Alzheimer's type
Use - Unlabeled/InvestigationalAttention-deficit/hyperactivity disorder (ADHD), behavioral syndromes in dementia
Pregnancy Risk FactorC
Pregnancy ImplicationsTeratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women.
LactationExcretion in breast milk unknown/not recommended
ContraindicationsHypersensitivity to donepezil, piperidine derivatives, or any component of the formulation
Warnings/PrecautionsCholinesterase 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/ToxicologyImplement 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 InteractionsSubstrate (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 InteractionsHerb/Nutraceutical: St John's wort may decrease donepezil levels.
Mechanism of ActionAlzheimer'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/KineticsAbsorption: 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)
DosageOral: 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 ParametersBehavior, mood, bowel function
Patient EducationThis 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.
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Additional InformationDonepezil does not significantly elevate liver enzymes.
Dental Health: Effects on Dental TreatmentNo significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic PrecautionsNo information available to require special precautions
Mental Health: Child/Adolescent ConsiderationsFive 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 FormsTablet, as hydrochloride: 5 mg, 10 mg
ReferencesHardan 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 NamesAricept® (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)
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A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited. |
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