Black Box Warnings: 11 AEDs Are Evaluated

The FDA announced its intention to push for a black box warning to be placed on the prescription label of 11 AEDs.

Last week, the FDA announced its intention to push for a black box warning to be placed on the prescription label of 11 AEDs based on a finding from the FDA that the medicines “are associated with a higher risk of suicidal thoughts and behavior.” The AEDs in question are:












Although the FDA has recommended a black box warning, an advisory panel of outside experts was also given the opportunity to provide its recommendations; the panel rejected putting a black box warning on the prescription information for AEDs. The panel’s main concern was that “a strong warning could scare epilepsy patients from being treated with effective drugs.”

Dr. Frank Gilliam, professor of neurology at Columbia University and a member of the national Professional Advisory Board of the Epilepsy Foundation, said, “We emphasize it is very important we recognize the apparently small additional risk of suicide due to AEDs as compared to the huge risk for not taking needed medications.” The panel did recommend that information about these risks should be sent to physicians and put on AEDs’ package inserts.

Black box warning education

Black box warnings are designed to alert physicians and patients of potential serious side effects related to a prescribed medication and are offset by a black border surrounding the text. Although a drug may carry a warning, physicians may still choose to treat their patients with it and do so “without conducting a detailed discussion of ‘black box’ warnings with the patient.” Lately, with black box warning announcements being made via the media, patients are becoming educated and bringing questions to their physicians.

The biggest problem that physicians face with regard to black box warnings is the difficulty in finding them outside of the information found on the package insert. The authors of an article in the January 2006 issue of The Journal of Allergy and Clinical Immunology identified the following black box-related issues:

• Black box warnings are not always found at the beginning of product information included in the Physicians Desk Reference and package insert

• It is difficult to locate a list of drugs that have black box warnings on the FDA website

• “Many physicians and patients may not be aware that certain drugs they are using have ‘black box’ warnings”

• Manufacturer and pharmacy information does not adequately highlight black box warnings

• There are no clear regulations requiring patients to be made aware of black box warnings

The authors offered the following recommendations based on discussions with healthcare experts about black box warnings:

• Physicians should come up with their own policy to keep patients aware of black box warnings

• The FDA should create a list of drugs that have black box warnings to be easily accessed on its website

• Pharmaceutical companies should give physicians information containing the relevant information “useful in making an informed decision around the application of the medicine”

• Medical societies should provide additional education about drug-specific black box warnings to physicians

• Patient education materials should be developed to ease the anxiety when black box announcements are made

Additional Resources

Dr. Orrin Devinsky’s ABC Interview

Seizure Safety and AEDs

FDA and AEDs in the News: Weighing the Risks and Benefits of Taking Antiepileptic Drugs for Epilepsy

Briefing Document for the July 10, 2008 Advisory Committee Meeting to Discuss Antiepileptic Drugs (AEDs) and Suicidality

What are your thoughts about the FDA’s recommendation to place black box warnings on 11 AEDs? Do you think it was a good idea for the panel of experts to vote against the recommendation? Have patients ever asked you about black box warnings?