donepezil

Donepezil is an oral medication used to treat mild, moderate, or severe dementia associated with 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 the progression of Alzheimer's disease.

Donepezil was approved by the FDA in 1996.

The most common side effects associated with donepezil are:

• headache,
• generalized pain,
• fatigue,
• dizziness,
• nausea,
• vomiting,
• diarrhea,
• loss of appetite,
• weight loss,
• muscle cramping,
• joint pain,
• insomnia, and
• increased frequency of urination.

Other important side effects include:

• seizures,
• fainting,
• abnormal heart beats, and
• stomach ulcers.

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. Mild to moderate disease is treated with 5 or 10 mg once daily. Moderate to severe Alzheimer's disease is treated with 10 or 23 mg daily.

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.

It is not known whether donepezil is harmful to the fetus. Safe use during pregnancy has not been established.

It is not known whether the donepezil is secreted into breast milk or if breastfeeding while taking donepezil is safe for the nursing infant.

What preparations of donepezil are available?

Tablets: 5, 10 and 23 mg. Tablets (orally disintegrating tablets): 5 and 10 mg.

How should I keep donepezil stored?

Tablets should be stored at room temperature, 15-30 C (59-86 F).