No

Acetylcholinesterase Inhibitor (Central)

Treatment of mild to moderate dementia of the Alzheimer's type

C

Hypersensitivity to donepezil or piperidine derivatives

Use with caution in patients with sick sinus syndrome or other supraventricular cardiac conduction abnormalities, in patients with seizures, COPD, or asthma; avoid use in nursing mothers. Use with caution in patients at risk of ulcer disease (ie, previous history or NSAID use), or in patients with bladder outlet obstruction. May cause diarrhea, nausea, and/or vomiting, which may be dose-related.

>10%:

Central nervous system: Headache

Gastrointestinal: Nausea, diarrhea

1% to 10%:

Cardiovascular: Syncope, chest pain, hypertension, atrial fibrillation, hypotension, hot flashes

Central nervous system: Fatigue, insomnia, dizziness, depression, abnormal dreams, somnolence

Dermatologic: Bruising

Gastrointestinal: Anorexia, vomiting, weight loss, fecal incontinence, GI bleeding, bloating, epigastric pain

Genitourinary: Frequent urination

Neuromuscular & skeletal: Muscle cramps, arthritis, body pain

<1% (limited to significant or life-threatening): Cholecystitis, seizures, hallucinations, heart block, hemolytic anemia, hyponatremia, pancreatitis, rash

General supportive measures; can cause a cholinergic crisis characterized by severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions; increased muscle weakness is a possibility and may result in death if respiratory muscles are involved

Tertiary anticholinergics, such as atropine, may be used as an antidote for overdosage. I.V. atropine sulfate titrated to effect is recommended; initial dose of 1-2 mg I.V. with subsequent doses based upon clinical response. Atypical increases in blood pressure and heart rate have been reported with other cholinomimetics when coadministered with quaternary anticholinergics such as glycopyrrolate.

CYP2D6 and 3A3/4 enzyme substrate

Phenytoin, carbamazepine, dexamethasone, rifampin, and phenobarbital may increase the rate of elimination of donepezil; monitor for altered clinical response

Anticholinergic agents (benztropine) may inhibit the effects of donepezil

A synergistic effect may be seen with concurrent administration of succinylcholine or cholinergic agonists (bethanechol)

Alzheimer's disease is characterized by cholinergic deficiency in the cortex and basal forebrain, which contributes to cognitive deficits. Donepezil reversibly and noncompetitively inhibits centrally-active acetylcholinesterase, the enzyme responsible for hydrolysis of acetylcholine. This appears to result in increased concentrations of acetylcholine available for synaptic transmission in the central nervous system.

Onset of action: May require extended treatment

Duration: May be prolonged, particularly in older patients

Absorption: Well absorbed

Half-life: 70 hours

Time to peak plasma concentration: 3-4 hours

Adults: Initial: 5 mg/day at bedtime; may increase to 10 mg/day at bedtime after 4-6 weeks

No information available to require special precautions

No effects or complications reported

This medication will not cure the disease, but may help reduce symptoms. Use as directed; do not increase dose or discontinue without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). May cause dizziness, sedation, or hypotension (rise slowly from sitting or lying position and use caution when driving or climbing stairs); vomiting or loss of appetite (frequent small meals, frequent mouth care, chewing gum, or sucking lozenges may help); or diarrhea (boiled milk, yogurt, or buttermilk may help). Report persistent abdominal discomfort; significantly increased salivation, sweating, tearing, or urination; flushed skin; chest pain or palpitations; acute headache; unresolved diarrhea; excessive fatigue, insomnia, dizziness, or depression; increased muscle, joint, or body pain; vision changes or blurred vision; or shortness of breath or wheezing. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Tablet: 5 mg, 10 mg

Rogers SL and Friedhoff LT, "The Efficacy and Safety of Donepezil in Patients With Alzheimer's Disease: Results of a U.S. Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial," Dementia, 1996, 7(6):293-303.