Petition to Recall Aricept 23mg Dose Rejected By FDA

The FDA has denied a petition filed by a consumer group, which had urged the federal drug regulators to ban Aricept 23, a high dose version of the top selling Alzheimer’s drug that provides questionable benefits over the lower dose and may increase the risk of potentially serious side effects.

In May 2011, the prominent consumer watchdog Public Citizen filed petition seeking an Aricept recall for the 23 milligram dose of the medication to treat moderate to severe dementia. The group also called for new warnings on lower doses of the drug.

Aricept (donepezil) is an acetylcholinesterase inhibitor, which is sold by Pfizer and Eisai, Inc. High doses of Aricept have been linked to a number of potential health risks, including lowered pulse, nausea, vomiting, diarrhea, urinary incontinence, fatigue, dizziness, agitation, confusion and anorexia. However, the group claims that there are little clinical benefits from using the higher doses over the lower ones.

In a response sent to Public Citizen on November 6, the FDA denied the petition to recall Aricept 23 (PDF) or add new warnings to the 5mg and 10mg doses.

“AD (Alzheimer’s Disease) is a devastating disease,” wrote Janet Woodcock, M.D., director of the FDA Center for Drug Evaluation and Research, in the letter denying the petition. “It affects patients, their families, and their caregivers, and no current treatment can completely ameliorate it. Donepezil (Aricept) is one of only two drugs indicated for treating the severe stage of the illness, and the 23 mg dose is shown to produce added cognitive benefits over the 10mg strength.”

In a statement issued by Public Citizen following the FDA denial, the group has sharply criticized the FDA and suggested that financial motivations may be behind keeping Aricept 23 on the market.

“Allowing drug manufacturer Eisai to exploit and harm vulnerable patients with Alzheimer’s disease is unconscionable,” wrote Dr. Sidney Wolfe, Director of Public Citizen’s Health Research Group, in a response issued November 6. “With close to $700 million in drug industry money a year directly funding the Food and Drug Administration (FDA) drug review process, the question is whether the FDA, in this instance, was protecting the public health or, in effect, colluding with the drug industry when it denied a petition to ban Aricept 23, deciding to leave the dangerous drug on the market.”

Aricept 23 Risks Outweigh Benefits, According to Public Citizen

Aricept is one of the biggest selling Alzheimer’s medications, resulting in more than $2.4 billion in sales in 2010 alone. To deny sale of the drug would cause a $700 million per year drug review process loss of funding for the FDA, according to Public Citizen.

The FDA approved the Aricept 23 milligram dose based on only one clinical trial, which Public Citizen states failed to show it is any more effective than lower doses. In three out of four tests, there was no significant difference between Aricept 10 mg and 23 mg doses in patients’ cognitive or functional level, and on the fourth test the difference was about 2 points on a scale of 100, which the group has argued is not clinically important.

At the higher doses, researchers have noted an increased incidence of side effects, such as gastrointestinal bleeding, esophageal rupture, and vomiting, which can lead to pneumonia, and in some cases death.

Considering this information, the primary medical reviewer and statistician at the FDA initially recommended denying the original application by the drug maker to introduce the higher dose version of Aricept. This recommendation was overruled by the director of the FDA’s Division of Neurology Products, Dr. Russell G. Katz, who approved the application and allowed Aricept 23 to go on the market.

Public Citizen has called the denial of the Aricept 23 recall petition a “reckless adherence to their original mistaken approval,” indicating that the FDA was needlessly endangering many elderly patients with Alzheimer’s with “a drug barely more effective but significantly more dangerous than the lower doses of Aricept.”

The FDA has maintained that any improvement of cognition in Alzheimer’s patients, however significant, may justify the potentially negative side effects. The decision to weigh the benefits against the risks is being largely left to the doctor’s of each individual patient.