A consumer advocacy group and professor of geriatric medicine are urging the Food and Drug Administration to yank the strongest dosage of a popular Alzheimer's medication from the market, because they're concerned that it is dangerous and ineffective.
Donepezil, which is marketed by Eisai and Pfizer under the brand name Aricept, has been approved by the FDA in 5 to 10 milligram (mg) doses for patients with mild to moderate cases of Alzheimer's disease, and doses of 10 to 23 mg for patients with moderate to severe Alzheimer's.In a petition to the FDA, Public Citizen is calling on the agency to immediately pull the 23 mg dose from the market due to the risk of "serious adverse effects" and its lack of efficacy. The group was joined by co-petitioner Dr. Thomas Finucane, a professor of medicine in the division of Gerontology and Geriatric Medicine at The Johns Hopkins University School of Medicine and a staff physician at the Johns Hopkins Bayview Medical Center.
"Data show that the 23-mg dose of donepezil is significantly more toxic than the 10-mg dose," Dr. Sidney Wolfe, director of Public Citizen's Health Research Group, said in a statement. "Combined with its lack of improved clinical benefits, this leads to only one conclusion: that the 23-mg dose should be immediately withdrawn from the market."
Compared to the 10-mg dose, Wolfe said, adverse side effects of Aricept 23 mg include a lower pulse rate, nausea, vomiting, diarrhea, urinary incontinence, fatigue, dizziness, agitation, confusion and anorexia. Vomiting -- which occurred more than 3.5 times as often in patients taking the 23-mg dose -- is especially dangerous for Alzheimer's patients, Wolfe added, since it can result in pneumonia, massive gastrointestinal bleeding, esophageal rupture and death.
In addition to having the 23-mg dose of Aricept pulled from pharmacy shelves, Public Citizen also wants the FDA to warn doctors and patients against taking 20 mg (two 10-mg pills) of the drug a day.
"We are aware of the petition, and it is important to note the 23 mg of Aricept has been approved by the FDA for the treatment of moderate to severe AD [Alzheimer's disease]," Marcia Diljak, an Eisai spokeswoman told Consumer Ally.
Dr. Finucane attributes Aricept's "multibillion-dollar success" to the desperation of family members caring for someone with Alzheimer's and the "relentless promotional campaign" for a drug he says should never have been approved in a 23-mg dose.
"When clinicians consider whether to initiate a therapeutic trial of a largely ineffective drug, the risk of harm should be a prominent consideration," Dr. Finucane said in a statement. "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."
Public Citizen says the sole clinical trial of Aricept 23 mg submitted to the FDA failed to prove it was more effective than the 10-mg dose. Three out of four tests found no significant difference between the 10- and 23-mg doses, and in the fourth test, the 23-mg dose bettered the 10-mg dose by just two points on a 100-point scale.
Alzheimer's patients stopped taking Aricept 23 mg due to harmful side effects at more than double the rate of those taking the 10-mg dose, Wolfe noted. And because of the drug's "very long" half-life, he added, it remains in patients' systems for approximately two weeks -- potentially delaying relief from adverse effects for those who stop taking the drug.
"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."
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