May 19, 2011 -- Public Citizen has petitioned the Food and Drug Administration to ban high doses of the Alzheimer's disease drug Aricept, claiming its risks far exceed its benefits.
The drug, made by Pfizer and Eisai, has been approved at doses of 5 to 10 milligrams for patients with mild to moderate Alzheimer's disease, and at doses of 10 to 23 milligrams for more severe cases.
The consumer advocacy group Public Citizen says that the side effects of the higher dose, which include slowed heart rate and vomiting, negate its modest advantage over the lower dose. But given the dearth of effective Alzheimer's treatments, some doctors believe the higher-dose option should stay on the table.
"In my opinion, it should be up to the consumer to decide whether to use this modestly effective, higher dose formulation of this drug," said Dr. Steven Ferris, executive director of the Alzheimer's Disease Center at New York University's Langone Medical Center. "Are there better treatments available? Clearly not at the present time."
Aricept and other generic cholinesterase inhibitors (which block the breakdown of neurotransmitters involved in memory and cognition) are considered the first line of defense in Alzheimer's treatment. If the lower dose is ineffective, the current options are to increase the dose, add a second drug (such as memantine) or join a clinical trial, according to Dr. Murali Doraiswamy, chief of biological psychiatry at Duke University Medical Center.
"Titrating up the dose of the first drug is usually the strategy most often used with other drugs such as antidepressants," Doraiswamy said, adding that he'd like to see more evidence that the benefits outweigh the risks before recommending high-dose Aricept widely.
Sandy Walsh, a spokeswoman for the FDA, said it "will review the petition and respond to the petitioner directly." It will aim to do this within 180 days.
The higher dose is recommended only for patients who have already taken a lower dose for at least three months.
Some doctors think the high dose should be allowed, but that patients should be screened for heart defects and gastrointestinal problems first.
"All drugs have side effects," said Niles Frantz, spokesman for the national Alzheimer's Association. "Individuals and their families, with their physician, must together determine what course of treatment is most worthwhile for them. These are choices best made by individuals and families."
In the trial on which the FDA based its approval, high-dose Aricept modestly improved patients' scores on a test that measured cognition. But it also boosted the occurrence of side effects.
"It is inexcusable that the FDA approved this higher dose. Its prompt removal would belatedly fulfill the agency's mission as part of the Public Health Service to only allow drugs whose benefits outweigh their risks to be marketed," said Dr. Sidney Wolfe, director of Public Citizen's Health Research Group, in a statement.
Public Citizen maintains that vomiting is a dangerous side effect for Alzheimer's patients, because it can lead to pneumonia.
But some doctors caution against basing decisions about drugs on anecdotal evidence.
"Every clinician is likely to have anecdotes regarding efficacy and adverse effects of this and other medications," said Dr. Paul Aisen, professor at University of California at San Diego and National Institute of Aging-appointed director of the Alzheimer's Disease Cooperative Study. "Decisions should be based on a rigorous, unbiased review of all available valid data. This is how the FDA operates. It is not how Public Citizen operates."
Wolfe also accuses the drugmakers of pushing the higher dose for financial gain.
"Given that the patent on Aricept, their big-selling, leading drug for Alzheimer's disease was due to expire in November 2010 and that Pfizer/Eisai judged they would quickly lose most of their market to less-expensive generic equivalents, what could they do? Getting a new patent on a previously unapproved higher dose, 23 milligrams, appeared to be the best idea," Wolfe said in a statement.
In response to the allegation, Marcia Diljack, a spokeswoman for Eisai, would say only that making the 23 milligram dose available is part of the companies' ongoing commitment to advancing Alzheimer's disease research and providing more options for Alzheimer's patients.