New Safety Warning For the Alzheimer’s Disease Drug Rivastigmine (EXELON)

In the January 2001 issue of Worst Pills, Best Pills News we recommended that the new Alzheimer’s disease drug rivastigmine (EXELON), the third such drug on the market, should not be used for at least five years. This would be April 2005. The two other Alzheimer’s drugs available in the U.S. are tacrine (COGNEX) and donepezil (ARICEPT).

On January 26, 2001, Novartis Pharmaceuticals Corporation notified health professionals that new warnings are being added to the professional product labeling or “package insert” concerning the risk of severe vomiting when rivastigmine treatment is stopped for some reason and then restarted at a later date.

In the controlled clinical trials conducted before the drug was cleared for marketing, 47 percent of patients treated with a rivastigmine dose in the range of 6 to 12 milligrams per day developed nausea. This figure compared to 12 percent of those receiving an inactive or dummy (placebo) drug. In all, 31 percent of the rivastigmine-treated patients developed at least one episode of vomiting compared to 6 percent of the placebo-treated patients. Vomiting was rated as severe in 2 percent of rivastigmine- treated patients.

There has been one report, since the drug was approved, of severe vomiting with rupture of the esophagus (the tube that connects the mouth and stomach) after restarting treatment with rivastigmine in a dose of 4.5 milligrams following eight weeks off the drug. The following information in bold type has been added to the drug’s package insert:

WARNINGS
Gastrointestinal Adverse Reactions
Exelon ® (rivastigmine tartrate) use is associated with significant gastrointestinal adverse reactions, including nausea and vomiting, anorexia [loss of appetite], and weight loss. For this reason, patients should always be started at a dose of 1.5 mg BID [two times a day] and titrated [slowly increased] to their maintenance dose. If treatment is interrupted for longer than several days, treatment should be reinitiated with the lowest daily dose to reduce the possibility of severe vomiting and its potentially serious sequelae (e.g., there has been one post-marketing report of severe vomiting with esophageal rupture following inappropriate reinitiation of treatment with a 4.5-mg dose after 8 weeks of treatment interruption).

Our well-known “five-year-rule” says you should not use a new drug until it has been on the market for at least five years because pre-market testing does not provide a large enough “statistical universe” to make it likely that hidden hazards will show, as has been the case with rivastigmine.

What You Can Do

If you or a family member who has been prescribed rivastigmine has had it stopped, make sure that if it is restarted that the dose is not greater than 1.5 milligrams two times a day.