Brands, Medical Use, Clinical Data
Drug Category
- Nootropic Agents
- Parasympathomimetics
Dosage Forms
- Tablet
- Tablet (orally disintegrating)
Brands / Synonyms
Aricept; Aricept ODT; Eranz
Indications
For management of symptoms associated with Alzheimer's Disease
Pharmacology
Donepezil is a centrally acting reversible acetyl cholinesterase inhibitor. Its main therapeutic use is in the treatment of Alzheimer's disease where it is used to increase cortical acetylcholine. It is well absorbed in the gut with an oral bioavailability of 100% and easily crosses the blood-brain barrier. Because it has a half life of about 70 hours, it can be taken once a day. Initial dose is 5 mg per day, which can be increased to 10 mg per day after an adjustment period of at least 4 weeks. Donepezil is a parasympathomimetic, specifically, a reversible cholinesterase inhibitor. Donepezil is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase. If this proposed mechanism of action is correct, donepezil's effect may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact. There is no evidence that donepezil alters the course of the underlying dementing process.
Mechanism of Action
Donepezil's proposed mechanism of action involves the increase of the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase.
Absorption
Donepezil is well absorbed with a relative oral bioavailability of 100% and reaches peak plasma concentrations in 3 to 4 hours.
Toxicity
Symptoms of overdose include severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, respiratory depression, collapse and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved.
Biotrnasformation / Drug Metabolism
Donepezil is metabolized by CYP 450 isoenzymes 2D6 and 3A4 in the liver and also undergoes glucuronidation. The main metabolite, 6-O-desmethyl donepezil, has been reported to inhibit AChE to the same extent as donepezil in vitro.
Contraindications
ARICEPT® is contraindicated in patients with known hypersensitivity to donepezil
hydrochloride or to piperidine derivatives.
Drug Interactions
Drugs that inhibit or Induce CYP 2D6 and CYP 3A4 may affect the concentration on Aricept.
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