Medication Guide App

Donepezil Hydrochloride

Pronunciation

Class: Parasympathomimetic (Cholinergic) Agents
VA Class: AU300
Chemical Name: 2,3-Dihydro-5,6-dimethoxy-2-[(1-(phenylmethyl)-4-piperidinyl)methyl]-1H-inden-1-one
Molecular Formula: C24H29NO3
CAS Number: 120014-06-4
Brands: Aricept

Introduction

Centrally active, reversible acetylcholinesterase inhibitor.1 2 3 7

Uses for Donepezil Hydrochloride

Alzheimer’s Disease

Palliative treatment of mild to moderate dementia of the Alzheimer’s type (Alzheimer’s disease, presenile or senile dementia).1 2 3 4 6 15

Slideshow: Flashback: FDA Drug Approvals 2013

Comparative studies have not been performed to date, but donepezil does not share the hepatotoxic potential of tacrine and may be preferable to tacrine as a first-line treatment because it can be administered once daily and does not require regular monitoring of liver function.5 6

Donepezil Hydrochloride Dosage and Administration

Administration

Oral Administration

Administer conventional or orally disintegrating tablets orally once daily, usually at bedtime.1 2

Administer with or without food.1 2

Orally disintegrating tablets: Place on tongue and allow to dissolve; follow with water.1

Donepezil hydrochloride orally disintegrating and conventional film-coated tablets are bioequivalent.1

Dosage

Available as donepezil hydrochloride; dosage expressed in terms of the salt.1

Adults

Alzheimer’s Disease
Oral

Initially, 5 mg daily.1 6 11

Some data suggest the possibility of additional benefit with higher (10 mg daily) dosage in some patients;1 2 6 12 however, additional benefit with the 10-mg dosage has not been demonstrated in controlled clinical studies.1 2 12 Adverse cholinergic effects are more likely with the 10-mg dosage.1 2

Daily administration of 10 mg should not be considered until patient has received 5 mg daily for 4–6 weeks, since occurrence of adverse effects may be influenced by the rate of increase in dosage.1 2 11

Special Populations

Hepatic Impairment

No specific recommendation for dosage adjustment.1

Cautions for Donepezil Hydrochloride

Contraindications

  • Known hypersensitivity to donepezil or piperidine derivatives or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Anesthesia

Potential for exaggerated succinylcholine-type muscle relaxation during anesthesia.1

Cardiac Effects

Cholinesterase inhibitors may produce bradycardia or heart block via vagotonic effects on the sinoatrial or AV nodes.1 May occur in patients with or without known cardiac conduction abnormalities.1 14 Syncope reported in patients receiving donepezil.1

GI Effects

Possible diarrhea, nausea, and vomiting, particularly at dosage of 10 mg daily.1

Potential for increased gastric acid secretion.1

Carefully monitor patients, especially those at increased risk for developing ulcers (e.g., those with history of peptic ulcer disease, those receiving concomitant NSAIA therapy), for symptoms of active or occult GI bleeding.1

GU Effects

Although not reported in clinical studies with donepezil, cholinomimetic agents may cause bladder outflow obstruction.1 14

Respiratory Effects

Use with caution in patients with a history of asthma or obstructive pulmonary disease.1

Neurologic Effects

Cholinomimetic agents may have the potential to cause generalized seizures; however, seizures also may be a manifestation of Alzheimer’s disease.1

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether donepezil is distributed into milk.1 Not indicated for use in nursing women.1

Pediatric Use

Safety and efficacy not established.1

Geriatric Use

Dementia of the Alzheimer’s type occurs principally in patients >55 years of age.1 The mean age of patients receiving donepezil in clinical studies was 73 years of age.1 No substantial differences in most adverse effects in patients ≥65 years of age relative to those <65 years of age.1

Common Adverse Effects

Nausea, diarrhea, insomnia, vomiting, muscle cramp, fatigue, anorexia.1

Interactions for Donepezil Hydrochloride

Metabolized by CYP3A4 and CYP2D6.1 Unlikely to cause clinically important induction or inhibition of CYP3A4 or CYP2D6; not known whether donepezil has any enzyme-induction potential.1

Drugs Highly Bound to Plasma Proteins

Pharmacokinetic interactions unlikely with drugs highly bound to plasma proteins.1

Drugs Affecting or Metabolized by Hepatic Enzymes

Unlikely to alter clearance of drugs metabolized by CYP3A4 or CYP2D6.1

Possible pharmacokinetic interaction (altered plasma donepezil concentrations) with CYP2D6 or CYP3A4 inducers or inhibitors.1

Specific Drugs

Drug

Interaction

Comments

Anticholinergic agents

Possible interference with activity of anticholinergic agents1

Carbamazepine

Possible induction of donepezil metabolism1

Cholinergic agonists (e.g., bethanecol)

Synergistic effect1

Cholinesterase inhibitors

Synergistic effect1

Cimetidine

No clinically important effects observed on pharmacokinetics of either drug with concomitant use1

Dexamethasone

Possible induction of donepezil metabolism1

Digoxin

No clinically important effects observed on pharmacokinetics of either drug with concomitant use1

Furosemide

Pharmacokinetic interactions (including protein binding interactions) unlikely1

Ketoconazole

Plasma donepezil concentrations increased by 36% with concomitant use; no change in ketoconazole pharmacokinetics1

Inhibition of donepezil metabolism observed in vitro1

Clinical importance not known1

Neuromuscular blocking agents (e.g., succinylcholine)

Exaggerated muscle relaxation1

Phenobarbital

Possible induction of donepezil metabolism1

Phenytoin

Possible induction of donepezil metabolism1

Quinidine

Inhibition of donepezil metabolism in vitro1

Clinical importance not known1

Rifampin

Possible induction of donepezil metabolism1

Theophylline

Pharmacokinetic interaction unlikely1

Warfarin

Pharmacokinetic interactions (including protein binding interactions) unlikely1

Donepezil Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Relative oral bioavailability is 100%.1

Orally disintegrating and conventional film-coated tablets are bioequivalent.1

Food

Food does not affect rate or extent of absorption when administered as conventional film-coated tablets.1 Effect of food on donepezil absorption after administration as orally disintegrating tablets has not been studied, but any effects are expected to be minimal; orally disintegrating tablets may be taken without regard to meals.1

Distribution

Plasma Protein Binding

Approximately 96% (mainly albumin [75%] and alpha1-acid glycoprotein [21%]).1

Elimination

Metabolism

Extensively metabolized to 4 major metabolites (2 known to be active) and a number of minor metabolites.1 Is metabolized by CYP2D6 and CYP3A4 and undergoes glucuronidation.1

Elimination Route

Eliminated in urine and feces (57 and 15%, respectively, over 10 days, with 28% still unrecovered; about 17% of the dose recovered in urine as unchanged drug).1

Half-life

About 70 hours.1

Special Populations

In patients with stable alcoholic cirrhosis, clearance appears to be reduced by about 20%.1

In patients with moderate to severe renal impairment (Clcr <22 mL/minute per 1.73 m2), clearance appears to be similar to that in healthy individuals.1

Stability

Storage

Oral

Tablets and Orally Disintegrating Tablets

15–30°C.1

Actions

  • Precise mechanism(s) of action in patients with dementia of the Alzheimer’s type not fully elucidated.1 Binds reversibly with and inactivates cholinesterases (e.g., acetylcholinesterase), thus inhibiting hydrolysis of acetylcholine1 3 6 7 10 11 12 15 and resulting in increased acetylcholine concentrations at cholinergic synapses.1 6

Advice to Patients

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 6

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Donepezil Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

5 mg

Aricept

Eisai, (also promoted by Pfizer)

10 mg

Aricept

Eisai, (also promoted by Pfizer)

Tablets, orally disintegrating

5 mg

Aricept ODT

Eisai, (also promoted by Pfizer)

10 mg

Aricept ODT

Eisai, (also promoted by Pfizer)

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Aricept 10MG Tablets (EISAI): 30/$302.74 or 90/$812.38

Aricept 23MG Tablets (EISAI): 30/$277.99 or 90/$809.96

Aricept 5MG Tablets (EISAI): 30/$304.91 or 90/$820.01

Donepezil HCl 10MG Dispersible Tablets (GREENSTONE): 30/$179.98 or 90/$499.99

Donepezil HCl 10MG Tablets (GREENSTONE): 30/$188.00 or 90/$524.96

Donepezil HCl 5MG Dispersible Tablets (GREENSTONE): 30/$179.98 or 90/$499.99

Donepezil HCl 5MG Tablets (GREENSTONE): 30/$179.99 or 90/$499.94

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions May 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Eisai Inc. Aricept (donepezil hydrochloride) tablets and orally disintegrating tablets prescribing information. Teaneck, NJ; 2005 Mar.

2. Eisai Inc. Aricept product monograph. Teaneck, NJ; 1997 Jan.

3. Bryson HM, Benfield P. Donepezil. Drugs Aging. 1997; 10:234-9. [PubMed 9108896]

4. Mohs RC. Donepezil: a viewpoint. Drugs Aging. 1997; 10:240.

5. Whitehouse PJ. Donepezil: a viewpoint. Drugs Aging. 1997; 10:240-1.

6. American Psychiatric Association. Practice guideline for the treatment of patients with Alzheimer’s disease and other dementias of late life. Am J Psychiatry. 1997; 154:1-39.

7. Caspi A. Donepezil, a novel therapy for Alzheimer’s disease. P&T. 1997; 22(Feb):70-4.

8. Rogers SL, Doody R, Mohs R et al. E2020 produces both clinical global and cognitive test improvement in patients with mild to moderately severe Alzheimer’s disease: results of a 30-week phase III trial. Neurology. 1996; 46:A217. [PubMed 8559362]

9. Doraiswamy PM. Current cholinergic therapy for symptoms of Alzheimer’s disease. Primary Psychiatry. 1996; Nov:56-68.

10. Brufani M, Filocamo L, Lappa S et al. New acetylcholinesterase inhibitors. Drugs Fut. 1997; 22:397-410.

11. Anonymous. Donepezil (Aricept) for Alzheimer’s disease. Med Lett Drugs Ther. 1997; 39:53-4. [PubMed 9187642]

12. Rho JP, Lipson LG. Focus on donepezil: a reversible acetylcholinesterase inhibitor for the treatment of Alzheimer’s disease. Formulary. 1997; 32:677-84.

13. Rogers SL, Friedhoff LT. The efficacy and safety of donepezil in patients with Alzheimer’s disease: results of a US multicentre, randomized, double-blind, placebo-controlled trial. The Donepezil Study Group. Dementia. 1996; 7(Nov-Dec):293-303. [PubMed 8915035]

14. Eisai Inc, Teaneck, NJ: Personal communication.

15. Small GW, Rabins PV, Barry PP et al. Diagnosis and treatment of Alzheimer disease and related disorders: consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer’s Association, and the American Geriatrics Society. JAMA. 1997; 278:1363-71. [IDIS 393115] [PubMed 9343469]

16. Doody RS, Stevens JC, Beck C et al. Practice parameter: management of dementia (an evidence-based review). Report of the quality standards subcommittee of the American Academy of Neurology. Neurology. 2001; 56:1154-66. [IDIS 463599] [PubMed 11342679]

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