World Library  
Flag as Inappropriate
Email this Article

Aricept

Article Id: WHEBN0001641141
Reproduction Date:

Title: Aricept  
Author: World Heritage Encyclopedia
Language: English
Subject: Pfizer, Dementia with Lewy bodies, Tardive dyskinesia, List of drugs: Aq-Ar, List of psychotropic medications, Counterfeit consumer goods
Collection:
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Aricept

Template:Drugbox

Donepezil, marketed under the trade name Aricept by its developer Eisai and partner Pfizer, and also marketed under the brand name DONEP by Alkem Pentacare, is a centrally acting reversible acetylcholinesterase inhibitor.[1] Its main therapeutic use is in the palliative treatment of Alzheimer's disease.[2] Common side effects include gastrointestinal upset. It has an oral bioavailability of 100% and easily crosses the blood–brain barrier. Because it has a biological half-life of about 70 hours, it can be taken once a day.

Medical uses


Alzheimer's disease

Currently, no definitive proof shows the use of donepezil or other similar agents alters the course or progression of Alzheimer's disease (AD). However, 6 to 12-month controlled studies have shown modest benefits in cognition and/or behavior.[3] Pilot studies have reported donepezil therapy may potentially have effects on markers of disease progression, such as hippocampal volume. Therefore, many neurologists, psychiatrists, and primary-care physicians use donepezil in patients with Alzheimer's disease. In 2005, the UK National Institute for Clinical Excellence (NICE) withdrew its recommendation for use of the drug for mild-to-moderate AD, on the basis of no significant improvement in functional outcome, quality of life, or behavioral symptoms. However, NICE revised its guidelines to suggest donepezil be used in moderate-stage patients for whom the evidence is strongest.

While the drug is currently indicated for mild to moderate Alzheimer's, evidence from two clinical trials also indicates it may be effective for moderate to severe disease. An example of this is a Karolinska Institute paper published in The Lancet in early 2006, which states donepezil improves cognitive function even in patients with severe AD symptoms.[4] In Oct. 2006 the U.S. Food and Drug Administration also approved Aricept for treatment of severe dementia.

Dosage

In mild to moderate Alzheimer’s Disease, a starting dose of 5 mg given once daily should be used. In a minimum of four to six weeks, an increase to 10 mg is recommended. The usual dose is 5 to 10 mg once daily. Moderate to severe AD indicates the same regimen, but in a minimum of three months, a patient may receive a dose of 23 mg once daily. Dementia patients should receive 5–10 mg once daily. The maximum daily dose is 23 mg once daily.[5] Clinicians should use caution in prescribing the maximum daily dose as the risk of severe side effects may outweigh the unclear clinical benefits.[6] In the UK, the maximum licensed dose is 10 mg.

Contraindications

Donepezil (Aricept) should be used with caution in patient with cardiac disease, cardiac conduction disturbances, chronic obstructive pulmonary disease, asthma, severe cardiac arrhythmias and sick sinus syndrome. Patients with gastrointestinal disorders should use caution because nausea or vomiting may occur. These symptoms may appear more frequent when initiating treatment or increasing the donepezil dose. Although occurrence of seizures is rare, patients who have a predisposition to seizures should be treated with caution.[5] The British Medical Journal (BMJ) cautioned that the largest dosage, 23 mg, was crafted to extend patent protection rather than for medical reasons,[7] and was not shown to be more effective compared to the 10 mg dose.

Other

Donepezil has been tested (off label) in other cognitive disorders, including Lewy body dementia,[8] and vascular dementia,[9] but it is not currently approved for these indications. Donepezil has also been found to improve sleep apnea in Alzheimer's patients.[10]

Donepezil has also been studied in patients with mild cognitive impairment, schizophrenia, attention deficit disorder, postcoronary bypass cognitive impairment, cognitive impairment associated with multiple sclerosis, CADASIL syndrome, and Down syndrome. A three-year National Institutes of Health trial in patients with mild cognitive impairment reported donepezil was superior to placebo in delaying rate of progression to dementia during the initial 18 months of the study, but this was not sustained at 36 months. In a secondary analysis, a subgroup of individuals with the apolipoprotein E4 genotype showed sustained benefits with donepezil throughout the study (Petersen 2005). At this time, though, donepezil is not indicated for prevention of dementia.

A 2001 study suggested that donepezil can improve speech in autistic children. The study found the speech of autistic children that was originally mildly to moderately affected appeared to improve with the use of donepezil.[11][12]

Adverse effects

Common side effects include bradycardia, nausea, diarrhea, anorexia, abdominal pain, and vivid dreams.

In 2006, Eisai, the manufacturer, issued a statement that a single vascular dementia study found a difference in the percentage of study participants who died in the donepezil group (1.7%) versus the placebo group (0%). This could be due to an unusually low death rate on the placebo group. An analysis of all three vascular dementia trials, according to Eisai, "shows no statistically significant differences in observed mortality rates between the donepezil and placebo groups."

A physician reported several cases of mania.[13]

Development and marketing

Research leading to the development of donepezil began in 1983 at Eisai, and the first Phase I clinical trial took place in 1989.[14] In 1996, Eisai received approval from the United States Food and Drug Administration (USFDA) for donepezil under the brand Aricept, which it co-marketed with Pfizer. As of 2011, Aricept was the world's best-selling Alzheimer's disease treatment.[15] The first generic donepezil became available in November 2010 with the USFDA approval of a formulation prepared by Ranbaxy Labs.[16] In April 2011 a second generic formulation, from Wockhardt, received tentative USFDA marketing approval.[17]

References

External links

  • Official Aricept product site
  • Aricept entry at Drugs.com
  • http://www.websciences.org/cftemplate/NAPS/archives/indiv.cfm?ID=20081395
  • 3D Molecular structure of Donepezil
  • PDB
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 



Copyright © World Library Foundation. All rights reserved. eBooks from World Library are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.