The US Food and Drug Administration has been accused of breaching its "own regulatory standard" by approving a new dose of Eisai and Pfizer's blockbuster Alzheimer's drug Aricept in 2010, despite causing more side effects and not showing significant superiority over the original doses.

The accusation is made in an article in the British Medical Journal which notes that in July 2010, just before the US patent on the blockbuster Aricept (donepezil) expired, the FDA approved a new 23mg dose for moderate to severe Alzheimer's disease, thereby extending its patent for three more years. Previously, the drug was only available in 5mg and 10mg doses.

According to the BMJ, the FDA and Eisai agreed that the 23mg dose would be approved only if it was shown to be superior to the 10mg dose "on both a cognitive and a global functioning measure". However, Lisa Schwartz and Steven Woloshin of the Center for Medicine and the Media at The Dartmouth Institute for Health Policy and Clinical Practice, argue that although Aricept 23 improved cognitive symptoms, it did not improve overall functioning, which suggests that the cognitive difference was not meaningful. Furthermore, the new dose caused more side effects, including nausea and vomiting.

Aricept 23 approved despite advisors' objections

The professors claim the new dose was approved "only over the objections of the FDA's medical and statistical reviewers" (an advisory committee rejected the drug) and that it offers "no meaningful added benefit, just more harm". They also point to "a stunningly erroneous statement" in an advertisement aimed at doctors which claims patients on the 23mg dose "experienced important clinical benefit on both measures [cognition and overall functioning]".

They go on to say that "nowhere – not in the direct-to-consumer or the physician advertisements, nor even in the FDA-approved label – are the great uncertainties about this drug acknowledged". It is now, or will soon be under consideration for approval in 16 countries in Asia and South America.

Profs Schwartz and Woloshin go on to say that Alzheimer's is an awful disease and "sadly, the available drugs don't work well. But that is no excuse for manipulating vulnerable patients, desperate family members, and their doctors to use a product that is most likely to cause net harm". They conclude that "to make good decisions about drugs, doctors and patients need the evidence. The FDA should not forget to give it to them."

The BMJ states that new material recently obtained by the authors from the FDA acknowledge that they made an error, stating: "the offending phrase was in the original label, and we don't recall how it slipped by, but we contacted the company as soon as it was brought to our attention, and they readily agreed to remove it". The agency added that "we are always interested in improving the content and clarity of our labelling, and appreciate being informed of any misleading or inaccurate statements that anyone may notice".

The New York Times quoted Marcia Diljak, a spokeswoman for Eisai, who declined to comment on the drug’s safety, but said the Japanese firm and Pfizer decided to develop a higher dosage of Aricept after the 10mg version was approved in 2005. “The hypothesis was that patients with more advanced Alzheimer’s disease could benefit from a higher dose of Aricept".