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Donepezil, marketed under the trade name Aricept® (Eisai), 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.
The clinical utility of donepezil is controversial. Presently, there is no proof that use of donepezil or other similar agents alters the course or progression of Alzheimer's disease. However, controlled studies have shown modest benefits in cognition and behavior with this and similar agents. Therefore, many neurologists, psychiatrists, and primary care physicians use donepezil in patients with Alzheimer's disease. As of the 22 March 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 that there is no significant improvement in functional outcome; of quality of life or of behavioral symptoms. However, these data conflict with those of other reports, as is often the case in medicine.
Donepezil is sometimes used in combination with Memantine, a new agent for Alzheimer's disease which is in the same chemical class. The response to both together is superior to either alone.
Donepezil has been tested in other disorders which cause dementia including Lewy body dementia and Vascular dementia, but it is not currently approved for these indications.
BBC NEWS | Health | Drug 'treats severe Alzheimer's'
A controversial drug used to treat mild to moderate Alzheimer's disease can also help in the later stages of the disease, Swedish research suggests.
A Karolinska Institute study of 194 patients published in the Lancet found donepezil could improve mental function in severe cases.
The drug is not licensed in the UK to treat severe Alzheimer's and the NHS may soon stop funding it in mild cases.
Campaigners say it should be available to those with all forms of Alzheimer's.
Written by Pharmacists Reviewed by Doctors:
GENERIC NAME: donepezil
BRAND NAME: Aricept, Aricept ODT
DRUG CLASS AND MECHANISM: Donepezil is an oral medication used to treat Alzheimer's disease. It belongs to a class of drugs called cholinesterase inhibitors that also includes tacrine (Cognex). Scientists believe that Alzheimer's disease may result from a deficiency in chemicals (neurotransmitters) used by nerves in the brain to communicate with one another. Donepezil inhibits acetylcholinesterase, an enzyme responsible for the destruction of one neurotransmitter, acetylcholine. This leads to increased concentrations of acetylcholine in the brain, and the increased concentrations are believed to be responsible for the improvement seen during treatment with donepezil. Donepezil improves the symptoms but does not slow down the progression of Alzheimer's disease. Donepezil was approved by the FDA in 1996.
GENERIC AVAILABLE: no
PREPARATIONS: Aricept is available in 5 and 10 mg tablets. Aricept ODT (orally disintegrating tablets) also are available in 5 and 10 mg tablets.
STORAGE: Tablets should be stored at room temperature, 15-30°C (59-86°F).
PRESCRIBED FOR: Donepezil is used for the treatment of mild to moderate dementia of the Alzheimer's type.
DOSING: Donepezil is generally taken once daily at night prior to retiring. Its absorption is not affected by food so that it may be taken with or without food.
DRUG INTERACTIONS: Drugs with anti-cholinergic properties that can cross into the brain, such as atropine, benztropine (Cogentin), and trihexyphenidyl (Artane) counteract the effects of donepezil and should be avoided during therapy with donepezil.
Donepezil is metabolized (eliminated) by enzymes in the liver. The rate of metabolism of donepezil may be increased by medications that increase the amounts of these enzymes, such as carbamazepine (Tegretol), dexamethasone (Decadron), phenobarbital, phenytoin (Dilantin), and rifampin (Rifadin). By increasing elimination, these drugs may reduce the effects of donepezil.
Ketoconazole (Nizoral) has been shown to block the enzymes in the liver that metabolize donepezil. Therefore, concurrent use of ketoconazole and donepezil may result in increased concentrations of donepezil in the body and possibly lead to donepezil side effects. Quinidine (Quinidex, Quinaglute) also has been shown to inhibit the enzymes that metabolize donepezil and may cause donepezil side effects.
PREGNANCY: It is not known whether donepezil is harmful to the fetus. Safe use during pregnancy has not been established.
NURSING MOTHERS: It is not known whether the donepezil is secreted into breast milk or if breast-feeding while taking donepezil is safe for the nursing infant.
SIDE EFFECTS: The most frequently reported side effects associated with donepezil include headache, generalized pain, fatigue, dizziness, nausea, vomiting, diarrhea, loss of appetite, weight loss, muscle cramping, joint pain, insomnia, and increased frequency of urination.
Tacrine (Cognex), another anticholinesterase medication used in the treatment of Alzheimer's disease, is associated with liver toxicity. Donepezil does not appear to be associated with liver toxicity.
Living with Alzheimer's is hard. But you've taken an important first step. With Aricept you are fighting back against Alzheimer's. Aricept works differently in different people.
Studies have shown that things like memory, thinking and behavior may:
Get better in small ways or stay the same
Get worse over time, but slower than expected
Continue to get worse as expected
If symptoms stay the same - or get worse over time but slower than expected - it can still mean Aricept is working.
Drug Effective For Severe Alzheimer's Disease: The drug donepezil can reverse some aspects of cognitive and functional deterioration seen in patients with severe Alzheimer's disease, according to a randomised trial published online (March, 2006) by The Lancet.
About 20% of Alzheimer's patients have severe dementia. As their health deteriorates they become less able to communicate, less mobile, and increasingly reliant on nursing care. Donepezil is used to treat mild-to-moderate Alzheimer's disease but its effectiveness in severe dementia has not been assessed until now.
In their trial Bengt Winblad (Karolinska Institutet, Huddinge, Sweden) and colleagues recruited Alzheimer's patients over 50 years of age from 50 nursing homes in Sweden. They assigned 95 patients to donepezil and 99 to a placebo for 6 months. The investigators found that those on donepezil had improved cognition and ability to carry out daily activities when compared with those on placebo. More patients on the active drug had side effects than those in the placebo group but these were usually transient and mild to moderate in severity.
Professor Winblad states: "Donepezil slows, and can reverse some aspects of deterioration of cognition and function in individuals with severe Alzheimer's who live in nursing homes."
Dementia and Memory Loss:
Q. Are there any new treatments in the pipe line for treating dementia and short-term memory loss? Specifically in the elderly.
A. Yes, there are many new agents in the pipeline, but how soon they will be ready for clinical use is not clear--that really depends on the U.S. Food & Drug Administration. The kinds of agents that are being investigated reflect the many different theories of memory loss, dementia, and Alzheimer's Disease (AD). Since most of the research has focused on AD, I will discuss that first.
Many researchers believe that AD is mainly due to the accumulation of "gunk" in the brain, called beta amyloid. Several new compounds that interfere with the formation and toxicity of beta amyloid are under investigation; e.g., droloksifen and estrogens. A vaccine that prevents formation of amyloid plaque (deposits formed from beta amyloid) , and even decreases existing plaques is now being tested in human subjects (Elan Corporation). Other researchers are focusing on the damaging role of so-called excitatory amino acids in AD, such as glutamate. Too much excitation from these naturally-occurring brain chemicals, and brain cells can literally be excited to death.
Drugs such as memantine (which is still being tested) and lamotrigine (an anti-seizure medication that is already available) are potential antidotes to this hyper-excitation. Still other researchers believe that AD results from an inflammatory process in the brain, and are testing various anti-inflammatory agents similar to Vioxx[rofecoxib], a pain reliever already on the market. In the near term, a new agent called galantamine [Reminyl] is probably going to be available soon. This has a mechanism of action similar to some agents already available for AD, such as donepizil (Aricept), which increase a critical brain chemical called acetylcholine. However, galantamine adds a second chemical action that could improve its efficacy.
Many other agents for AD are in the works, and you may want to contact the Alzheimer's Association (http://www.alz.org/) for more information. Meanwhile, a variety of cognitive enhancers are being developed that might benefit individuals with milder degrees of memory impairment; e.g., a compound with the lyrical name, SB 271046 is now in the early stage of investigation (SmithKline Beecham). Herbal agents, such as gingko biloba, are also being investigated as cognitive enhancers; however, the public should be wary about claims in the lay press about such natural remedies. Since the FDA does not monitor these over-the-counter agents, the public needs to be cautious before using them. Some may have unexpected side effects; e.g., gingko can affect blood clotting.