By Rita R. Robison, Consumer Specialist
A drug used to treat moderate or severe cases of Alzheimer’s disease should be removed from the market immediately because of its risk of serious adverse effects and its lack of effectiveness, Public Citizen and a geriatrician from Johns Hopkins said in a petition filed this week with the Food and Drug Administration.
Donepezil, also known as Aricept, has been approved by the FDA in a dose of 5 to 10 milligrams for patients with mild to moderate cases of Alzheimer’s disease and in a dose of 10 or 23 mg for patients with moderate to severe Alzheimer’s. Public Citizen is calling for the 23-mg dose to be immediately pulled from the market.
"Data show that the 23-mg dose of donepezil is significantly more toxic than the 10-mg dose," Sidney Wolfe, M.D., director of Public Citizen’s Health Research Group, said in a statement.
Public Citizen is also asking the FDA to warn doctors and patients against taking 20 mg of the drug – two 10-mg pills – a day, even if Aricept 23 is removed from pharmacy shelves.
"Cholinesterase inhibitors such as Aricept have gained multibillion-dollar success due primarily to two factors: the understandable desperation of those who care for patients with Alzheimer’s disease and a relentless promotional campaign by drug companies," said Thomas Finucane, M.D., professor of medicine in the Division of Gerontology and Geriatric Medicine at The Johns Hopkins University School of Medicine.
"When clinicians consider whether to initiate a therapeutic trial of a largely ineffective drug, the risk of harm should be a prominent consideration," Finucane said. "The clearly increased risk of harm from Aricept 23-mg compared to Aricept 10-mg is so great, coupled with the lack of any evidence of improved benefit, that I believe it should not have been approved for sale to the families and caregivers of Alzheimer patients."
The only clinical trial of donepezil submitted to the FDA for approval showed there was no significant difference between the 10- and 23-mg doses, Wolfe said.
Increased adverse effects of the 23-mg dose of donepezil compared to the 10-mg dose include a slowed pulse rate, nausea, vomiting, diarrhea, urinary incontinence, fatigue, dizziness, agitation, confusion, and anorexia, Wolfe said.
"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, a conclusion reached by both the FDA medical officer and statistician," Wolfe said. "It is inexcusable that the 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."