Risk of Overdose — Rivastigmine Transdermal (Exelon) Patch for Alzheimer’s Disease

The U.K. and Canadian equiva­lents of the Food and Drug Ad­ministration (FDA) recently issued warnings concerning serious side effects related to the misuse of the rivastigmine patch that have resulted in overdose.

The rivastigmine patch (EXELON) was approved by the FDA in July 2007 for the treatment of mild to moderate Alzheimer’s disease and mild to moderate dementia as­sociated with Parkinson’s disease. Rivastigmine also is available in an oral dosage form. For a long time, we have advised Worst Pills, Best Pills News readers not to use the oral form of this drug because of the lack of any important benefit combined with the high incidence of side effects. The FDA physician who reviewed this older version of the drug stated in 2000, before its approval, “I recom­mend that this application not be approved on the grounds that the risks of using the drug outweigh the possible benefits.”

Health Canada, the Canadian equivalent of the FDA, reported that as of July 31, 2009, a total of 129 cases of medication errors or misuse, including two fatal cases, had been reported for the rivastigmine patch worldwide. The most frequently reported causes of overdose are failure to remove the patch before applying a new one and application of more than one patch at the same time.

Symptoms of rivastigmine overdose

Below are the symptoms of rivastig­mine overdose:

• nausea
• vomiting
• diarrhea
• high blood pressure
• hallucinations
• slow heart rate (bradycardia) and/or fainting, associated with malaise or falls, may also occur

In cases of suspected overdose, all rivastigmine patches should be removed immediately, and no further patch should be applied for the fol­lowing 24 hours. (The duration of patch activity is 24 hours.)

Severe gastrointestinal (GI) adverse reactions to the rivastigmine patch

The rivastigmine patch, when given in higher-than-recommended doses, is associated with significant GI adverse reactions, including nausea, vomiting, diarrhea, decreased appetite and weight loss. For this reason, the rivastigmine patch should always be started at a dose of 4.6 milligrams per 24 hours and then increased to a dose of 9.5 milligrams per 24 hours. If treatment is stopped for longer than several days, treatment should be restarted with the lowest daily dose to reduce the possibility of severe vomiting and its potentially seri­ous results. For example, there was one post-marketing report (a report received by the FDA after a drug has been released for use in the general population) of severe vomiting with esophageal rupture following the inappropriate restarting of treatment with a low dose of the oral formula­tion of rivastigmine after eight weeks of treatment interruption.

The rivastigmine patch is minimally effective

A single major trial was used by the FDA as the basis for approval of the rivastigmine patch. In the trial, the efficacy of the patch was measured using the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog), a multi-item survey. The ADAS-Cog examines selected aspects of cognitive performance, including elements of memory, orientation, attention, reasoning and language. The ADAS-Cog scoring range is from 0 to 70, with higher scores indicating greater cognitive impairment. Elderly adults without cognitive impairment may score as low as 0 or 1.

In this trial, which lasted 24 weeks, two different doses of the rivastig­mine patch and 6 milligrams of the oral form of the drug were compared to a placebo. At the end of 24 weeks, compared to the placebo, the average difference in the ADAS-Cog scores was 1.8 units (out of 70) with a patch that delivered 9.5 milligrams per 24 hours, 2.9 units with a patch that de­livered 17.4 milligrams per 24 hours and 1.8 units with a capsule that delivered 6 milligrams per 24 hours. The dosage of 17.4 milligrams per 24 hours is not marketed.

The difference between each of the groups and the placebo was statisti­cally significant, meaning that it is unlikely, but not impossible, that the result of the study is due to chance or luck. The clinical relevance of this is that a change this small is not likely to be detected either by the patient’s family members or physician.

We have listed the rivastigmine patch and other Alzheimer’s disease drugs as Do Not Use because of their extremely limited efficacy.

What You Can Do

We continue to list both the oral form and the patch form of rivastig­mine as Do Not Use drugs; however, if they are still being used, follow these guidelines:

• Rivastigmine patches should be replaced after 24 hours, and the previous day’s patch must be removed before the application of a new patch to a different skin location.
• Application to the same skin location within 14 days should be avoided to minimize skin irritation.
• The patch should not be cut into pieces.

Consumers may report serious ad­verse events or product-quality prob­lems with the use of the rivastigmine patch or other products to the FDA’s MedWatch Adverse Event Reporting program either online or by regular mail, fax or phone.

Online: https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
Regular Mail: Use postage-paid FDA form 3500 and mail to Med­Watch, 5600 Fishers Lane, Rockville, MD 20852-9787
Fax: (800) FDA-0178
Phone: (800) FDA-1088