Oral Mild dementia in Alzheimer's disease, Moderate dementia in Alzheimer's disease, Severe dementia in Alzheimer's disease
Adult: Initially, 5 mg once daily at bedtime, may increase after 1 mth to 10 mg once daily, if necessary. Max: 10 mg daily. Elderly: Initially, 5 mg daily at bedtime, increase if necessary up to 10 mg once daily at bedtime after 4-6 wk.
Administration
May be taken with or without food. Take in the evening just prior to retiring. 23-mg tab: Swallow whole, do not split/crush/chew. ODT: Allow to dissolve on the tongue & follow w/ water.
Special Precautions
Patient w/ history of asthma or COPD, sick sinus syndrome, supraventricular conduction abnormalities, susceptibility to peptic ulcer, seizures, GI or urinary tract obstruction. Hepatic impairment. Pregnancy and lactation.
Monitor mental status, wt, pulse, symptoms of GI intolerance or bleeding.
Overdosage
Symptoms: Cholinergic crisis characterised by severe nausea, vomiting, salivations, sweating, bradycardia, hypotension, resp depression, collapse, convulsion, muscle weakness. Management: Supportive treatment and use of anticholinergic such as IV atropine.
Drug Interactions
Increased risk of neuroleptic malignant syndrome w/ antipsychotics. Synergistic effect w/ succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists (e.g. bethanechol). May interfere w/ the activity of anticholinergic medications. Increased plasma concentration when used w/ CYP3A4 inhibitors (e.g. ketoconazole, erythromycin) and CYP 2D6 inhibitors (e.g. fluoxetine, quinidine). Decreased plasma concentrations w/ enzyme inducers (e.g. rifampicin, phenytoin).
Action
Description: Donepezil reversibly and noncompetitively inhibits centrally-active acetylcholinesterase that is responsible for the hydrolysis of acetylcholine, resulting to increased concentration of acetylcholine in the CNS. Pharmacokinetics: Absorption: Well absorbed from the GI tract. Time to peak plasma concentration: 3-4 hr. Distribution: Volume of distribution: 12-16 L/kg. Protein binding: Approx 96% (to albumin (75%) and α1-acid glycoprotein (21%). Metabolism: Extensively metabolised in the liver, mainly by CYP3A4 isoenzyme and to a lesser extent by CYP2D6, into 4 major metabolites. Excretion: Via urine (57%, as unchanged drug and metabolites) and faeces (15%). Elimination half-life: Approx 70 hr.
Chemical Structure
Source: National Center for Biotechnology Information. PubChem Database. Donepezil, CID=3152, https://pubchem.ncbi.nlm.nih.gov/compound/Donepezil (accessed on Jan. 21, 2020)
N06DA02 - donepezil ; Belongs to the class of anticholinesterases. Used in the management of dementia.
References
Anon. Donepezil. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 09/11/2016.Aricept Solution (Eisai Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 09/11/2016.Buckingham R (ed). Donepezil Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com . Accessed 09/11/2016.Donepezil Hydrochloride 5 mg and 10 mg Tablet, Film Coated (Major Pharmaceuticals). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 09/11/2016.Donepezil Hydrochloride Tablet, Film Coated (Camber Pharmaceuticals, Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 09/11/2016.Joint Formulary Committee. Donepezil hydrochloride. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/11/2016.McEvoy GK, Snow EK, Miller J et al (eds). Donepezil Hydrochloride. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 09/11/2016.
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