Known brand names include Aricept.
A once-daily tablet or orally disintegrating tablet for dementia of the Alzheimer type, at mild, moderate, or severe stages. It blocks the enzyme that breaks down acetylcholine, a chemical messenger in the brain, which can ease symptoms but has not been shown to change the course of the disease.
Labeled use. Dementia of the Alzheimer type at mild, moderate, and severe stages.
Sources: [1]
Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are first-line symptomatic therapy for Alzheimer dementia, with similar modest benefit; donepezil's once-daily dosing and labeling for all stages make it a common first choice. Memantine is added or used for moderate to severe disease. Rivastigmine also comes as a patch, which can help when GI effects or swallowing pills are a problem. Use caution with bradycardia, conduction disease, syncope, or other rate-slowing drugs.
A reversible acetylcholinesterase inhibitor. Slowing acetylcholine hydrolysis raises acetylcholine levels and is thought to enhance cholinergic transmission, which is deficient in Alzheimer disease; there is no evidence it alters the underlying disease. Half-life is about 70 hours with steady state within 15 days; it is metabolized by CYP2D6, CYP3A4, and glucuronidation, and about 17% of a dose is excreted unchanged in urine.
The label does not describe a narrow therapeutic index or direct dosing by measured blood levels of the drug.
Sources: [1]
Sources: [1]
Doses come from the FDA label. Study tool, not for clinical decisions.
No adjustment. In 11 patients with moderate to severe renal impairment, clearance did not differ from matched healthy subjects.
Sources: [1]
No dose adjustment is given. In stable alcoholic cirrhosis, clearance fell by 20% compared with healthy subjects.
Sources: [1]
Atropine, a tertiary anticholinergic, is the antidote: IV atropine sulfate titrated to effect, starting with 1.0 to 2.0 mg IV. Overdose causes cholinergic crisis with slow heart rate, low blood pressure, severe nausea and vomiting, drooling, sweating, depressed breathing, collapse, and seizures; rising muscle weakness can be fatal if breathing muscles are involved. Give general supportive care. Quaternary anticholinergics such as glycopyrrolate have caused atypical blood pressure and heart rate responses with other cholinomimetics, and whether dialysis removes donepezil is unknown.
Sources: [1]
There are no adequate human data. Animal studies showed no birth defects when given during organogenesis, but dosing rats late in pregnancy and through lactation increased stillbirths and reduced pup survival at clinically relevant doses.
Sources: [1]
No data on donepezil in human milk, effects on breastfed infants, or milk production. Weigh the benefits of breastfeeding against the mother's need for the drug and possible effects on the infant.
Sources: [1]
Most study patients were older adults (mean age 73; 80% aged 65 to 84), and adverse reactions did not differ meaningfully between those 65 and older and younger patients. Clearance falls with age (17% lower at 90 than at 65), which may not matter clinically. On 23 mg, patients under 55 kg had more nausea, vomiting, and weight loss.