pharmacologic class: reversible inhibitor of
acetylcholinesterase
Therapeutic class: psychotherapeutic agent for
Alzheimer's disease
Pregnancy risk category: C
How supplied
Tablets: 5 mg. 10 mg
Pharmacokinetics
Absorption: well absorbed.
Distribution: 96% plasma protein-bound, mainly to
albumin.
Metabolism: extensively metabolized.
Excretion: in urine and feces.
Pharmacodynamics
Chemical effect: reversibly inhibits acetylcholinesterase
in the CNS. thereby increasing the concentration of
acetylcholine.
Therapeutic effect: temporarily improves the cognitive
function in patients with Alzheimer's disease.
Indications and
dosage
Mild to moderate dementia of the Alzheimer's
type.
Adults: initially. 5 mg P.O. daily h.s. After 4 to 6
weeks. may increase dosage to 10mg daily.
Adverse reactions
CNS: headache, insomnia, dizziness, depression,
abnormal dreams, somnolence, seizures, tremor,
irritability, paresthesia. aggression, vertigo, ataxia, increased
libido, restlessness, abnormal crying, fatigue, nervousness,
aphasia.
CV: syncope. chest pain, hypertension. vasodilation,
atrial fibrillation, hot flashes, hypotension.
EENT: cataract, blurred vision, eye irritation.
GI: nausea, diarrhea, vomiting, anorexia, fecal
incontinence. GI bleeding, bloating, epigastric pain.
GU: frequent urination.
Hematologic: ecchymosis.
Musculoskeletal: muscle cramps, arthritis, toothache,
bone fracture.
Respiratory: dyspnea, sore throat,
bronchitis.
Skin: pruritus, urticaria, diaphoresis.
Other: pain, accident, weight decrease, influenza,
dehydration.
Interactions
Drug-drug.
Anticholinergics: may interfere with anticholinergic
activity. Monitor patient.
Bethaechol, succinylcholine: additive effects. Monitor
patient closely.
Carbamazepine, dexamethasone, rifampin, phenytoin,
phenobarbital: may increase rate of elimination of donepezil.
Monitor patient.
Cholinomimetics, cholinesterase inhibitors: synergistic
effect. Monitor patient closely.
Contraindications and precautions
Contraindicated in patients with known hypersensitivity to drug or to piperidine derivatives.
Use cautiously in patients with history of ulcer disease, CV disease, asthma or obstructive pulmonary disease, or urinary outflow impairment and in those currently taking NSAIDs.
Several years ago the NIH conducted a test using Aricept (Donepezil) to treat patients diagnosed with PSP. Many in the test experienced serious side-effects that resulted in the recommendation that Aricept (Donepezil) not be used to treat the symptoms of PSP. Still, it is often prescibed off- label by doctors who are probably not aware of the rcommendation. For additional information on the trial to treat PSP with Aricept go here.
Both of these trials are sponsored by the drug's maker hoping to secure FDA approval to use this drug for other diseases in addition to its approved use to treat Alzheimer's.
This article should realert all to the fact that being a human guinea pig is not always a wise decision. Untested and unapproved uses of medications off-label are often more dangerous than any trial participant realizes.
I know.
I lost my oldest son in 2001 due to liver failure which was probably caused by his decision to try almost anything that might help make him well. By doing so he destroyed his liver. I had warned him about the dangers but a father isn't always listened to.
Ron Ritch
CHICAGO - March 16, 2006 - Eleven patients have died while taking Alzheimer's disease drug Aricept during a clinical trial, Japan's Eisai Co., which makes the medicine, said Thursday.
There were no deaths among patients who were taking a placebo, said Eisai, which markets Aricept with Pfizer Inc.
The drug, which treats mild to moderate Alzheimer's disease, was being tested in patients with vascular dementia, the second most common form of dementia after Alzheimer's disease.
Applications to expand the use of Aricept to vascular dementia, which is caused by a stroke or diseased blood vessels, are pending in both the United States and Europe, said Eisai spokeswoman Judee Shuler.
"We are still working with the FDA (U.S. Food and Drug Administration), discussing it," she said.
Shuler said she could not comment on how the results might affect the status of Aricept. Pfizer officials were not immediately available.
Aricept is approved for vascular dementia in a half-dozen smaller markets, including South Korea and India.
The deaths were among 648 patients who received Aricept once daily for 24 weeks. That compared with no deaths in the 326 patients receiving placebos, Eisai said in a release.
The difference in mortality between the groups was statistically significant, meaning it probably was not due to chance.
The trial is a Phase 3 study, the final period of testing before companies present proposals to regulators for approval.
It was conducted in nine countries and involved only patients with vascular dementia, with no prior diagnosis of Alzheimer's disease. Most had a history of stroke or heart disease, and were therefore also taking medicines to treat their cardiovascular problems.
Eisai said it had not expected the absence of deaths in the placebo group, considering the age and sickness of patients in the study. By contrast, the company said there had been a combined 2 percent incidence of death among patients taking placebos in two prior vascular dementia trials.
The incidence of death in the Aricept group was similar to that in prior trials. But in these earlier studies, the difference between placebo deaths were not statistically significant.
Patients taking Aricept in the latest trial showed a statistically significant improvement in cognitive function, compared with those taking placebos. But the Aricept group showed no significant benefit on another primary measure of the trial, known as global function.
