Overview
11 DESCRIPTION Donepezil hydrochloride is a reversible inhibitor of the enzyme acetylcholinesterase, known chemically as (±)-2, 3-dihydro-5, 6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1 H -inden-1-one hydrochloride. Donepezil hydrochloride is commonly referred to in the pharmacological literature as E2020. It has an empirical formula of C 24 H 29 NO 3 HCl and a molecular weight of 415.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Current theories on the pathogenesis of the cognitive signs and symptoms of Alzheimer's disease attribute some of them to a deficiency of cholinergic neurotransmission. Donepezil hydrochloride 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. There is no evidence that donepezil alters the course of the underlying dementing process. 12.3 Pharmacokinetics Pharmacokinetics of donepezil are linear over a dose range of 1 to 10 mg given once daily. The rate and extent of absorption of donepezil hydrochloride tablets are not influenced by food.
Indications
- 1 INDICATIONS AND USAGE Donepezil hydrochloride tablet is an acetylcholinesterase inhibitor indicated for the treatment of dementia of the Alzheimer's type. Efficacy has been demonstrated in patients with mild, moderate, and severe Alzheimer's Disease ( 1 ). Donepezil hydrochloride tablet is indicated for the treatment of dementia of the Alzheimer's type. Efficacy has been demonstrated in patients with mild, moderate, and severe Alzheimer's disease.
Common Doses
- 5 mg
- 10 mg
- 23 mg
Dosage
2 DOSAGE AND ADMINISTRATION Mild to Moderate Alzheimer's Disease: 5 mg to 10 mg once daily ( 2.1 ) Moderate to Severe Alzheimer's Disease: 10 mg to 23 mg once daily ( 2.2 ) 2.1 Dosing in Mild to Moderate Alzheimer’s Disease The recommended starting dosage of donepezil hydrochloride tablet is 5 mg administered once per day in the evening, just prior to retiring. The maximum recommended dosage of donepezil hydrochloride tablets in patients with mild to moderate Alzheimer's disease is 10 mg per day.
Contraindications
- 4 CONTRAINDICATIONS Known hypersensitivity to donepezil hydrochloride or to piperidine derivatives ( 4 ) Donepezil hydrochloride is contraindicated in patients with known hypersensitivity to donepezil hydrochloride or to piperidine derivatives.
Side Effects
- 6 ADVERSE REACTIONS Most common adverse reactions in clinical studies of donepezil hydrochloride are nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue, and anorexia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/ medwatch . The following serious adverse reactions are described below and elsewhere in the labeling: Cardiovascular Conditions [ see Warnings and Precautions ( 5.2 ) ]. Nausea and Vomiting [ see Warnings and Precautions ( 5.3 ) ].
Interactions
- 7 DRUG INTERACTIONS Cholinesterase inhibitors have the potential to interfere with the activity of anticholinergic medications ( 7.1 ). A synergistic effect may be expected with concomitant administration of succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists ( 7.2 ). 7.1 Use with Anticholinergics Because of their mechanism of action, cholinesterase inhibitors have the potential to interfere with the activity of anticholinergic medications. 7.