About Aricept
(Donepezil)
Aricept, which is claimed to be the #1 prescription drug
against Alzheimer’s disease in the USA these days, belongs to the class of
chemical substances, called cholinesterase inhibitors. It could be thrilling to
note, that during World War II the representatives of this very group of
chemicals were mainly developed for warfare purposes: such terrifying and
deadly weapons as neuroparalytic gases sarin, soman, and VX also belong to the
class of cholinesterase inhibitors.
Happily, nowadays the properties of cholinesterase
inhibitors are used mainly for peaceful purposes; one of them is to help people
conquer Alzheimer’s
disease - one of the most devastating mental illnesses of elderly people.
Today there are three substances of cholinesterase inhibitors
group, which are approved for medicinal use – donepezil, galantamine and rivastigmine.
However, it is only donepezil or Aricept as the brand medication, which is
approved for the use in patients on all stages of Alzheimer’s disease (others
are used only for mild to moderate conditions). Donepezil is said to be the
most potent among other representatives of cholinesterase inhibitors.
Aricept was developed by Eisai Inc. and approved by the FDA
in 1996. It is currently co-promoted by Eisai Inc. and Pfizer Inc.
There is a preliminary research data claiming that combination
Aricept and memantine,
another anti-Alzheimer’s medication, may significantly increase the
effectiveness of the treatment.
Aricept as Alzheimer’s
Treatment
As was mentioned
earlier, Aricept is part of a group of drugs called acetycholinesterase
inhibitors used to treat mild to moderate cognitive symptoms of
Alzheimer’s. There is no clinical evidence that it can actually alter the
course of the disease or help repair damaged brain cells.
It is believed that the chemical acetylcholine, which
transmits messages between brain cells in the area responsible for memory and
acquiring new information, is reduced in the brains of people with Alzheimer’s
disease.
Acetycholinesterase inhibitors, such as Aricept, help
prevent the breakdown of this important chemical, therefore helping to delay
deterioration. In some cases it has delayed symptoms by around 12 months.
In one study where some people received Aricept and others
received a placebo, those who took the drug were twice as likely to show some
improvement in thinking and understanding. For many it delayed their decline
for up to 12 months.
For some people the drug doesn’t have any effect at all or,
if it does, their condition stays the same when it could have been expected to
deteriorate.
And it doesn’t have any effect in the later stages of
Alzheimer’s because there are so few acetylcholine-producing cells left.
The drug is only available in prescription form and it’s up
to a doctor to decide whether it’s suitable for the individual Alzheimer’s
sufferer.
Dosage
Aricept is available in tablet form or an orally
disintegrating tablet form, and is commonly started at 5 mg a day. If it's well
tolerated after 4 to 6 weeks, the dosage may be increased to 10 mg a day.
Aricept has been
approved by the FDA in dosages of 5 to 10 milligrams for patients with mild to
moderate cases of Alzheimer's and in a dose of 10 to 23 milligrams for more
severe cases. There are ongoing efforts requesting FDA to ban the 23-mg version
of the drug and to warn patients and physicians against taking two 10-mg. pills
per day if the higher dosage is removed from the market.
Clinical trials
of Aricept submitted to the FDA for approval show no significant benefit from
the 23-mg version compared to the 10-mg version. But the increased adverse
effects from the higher dosage include a slowed pulse rate, nausea, vomiting,
diarrhea, urinary incontinence, fatigue, dizziness, agitation, confusion and
anorexia. Vomiting, which occurred more than 3 1/2 times more frequently in
those taking the high dosage, is a particularly dangerous side effect for
Alzheimer's patients, because it can lead to pneumonia, massive
gastrointestinal bleeding, esophageal rupture and even death.
"With no
evidence of an added advantage in benefit to patients, the clear increase in
risk should have been more than adequate grounds for denying approval,"
said Dr. Sidney Wolfe, director of Public Citizen's Health Research Group.
"It is inexcusable that FDA approved this higher dose. Its prompt removal
would belatedly fulfill the agency's mission to allow only drugs whose benefits
outweigh their risks to be marketed."
Side Effects
While applied to the normal doses of the drug, side effects
of the drug are generally well-tolerated. Nausea, vomiting, diarrhea, loss of
appetite/weight loss, dizziness, drowsiness, weakness, trouble sleeping,
shakiness (tremor), or muscle cramps may occur as your body adjusts to the
drug. These effects usually last 1-3 weeks and then lessen. If any of these
effects persist or worsen, notify your doctor or pharmacist promptly. Remember
that your doctor has prescribed this medication because he or she has judged
that the benefit to you is greater than the risk of side effects.
Many people using this medication do not have serious side
effects. Tell your doctor right away if any of these serious side effects
occur: slow/irregular heartbeat, fainting, trouble urinating, severe stomach/abdominal
pain, black stools, vomit that looks like coffee grounds, seizures. A very serious
allergic reaction to this drug is rare. However, get medical help right away if
you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling
(especially of the face/tongue/throat), severe dizziness, trouble breathing.
This is not a complete list of possible side effects. If you
notice other effects not listed above, contact your doctor or pharmacist.
Potential 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.
Non-steroidal anti-inflammatory drugs (NSAIDs), such as
aspirin or ibuprofen, also should be used with caution while taking Aricept,
due to the increased risk of stomach ulcers.
Sources and Additional
Information:
