Points for Discussion
Nonprescription Drugs Advisory Committee
September 19, 2002
Food and Drug Administration
Center for Drug Evaluation and Research
Hilton, Silver Spring Maryland
Issue: Unintentional Acetaminophen Hepatotoxicity
The Agency is in the process of writing a final regulation for internal analgesic drug products in the OTC drug review. This process began in 1977 with publication of the expert panel report and continued in 1988 with publication of the tentative final monograph. As part of the continuing review of this monograph, it is important to look at recent data pertinent to several safety issues that have been discussed in previous federal register notices
The Agency continues to believe that acetaminophen is a safe and effective OTC analgesic that benefits tens of millions of consumers every year. Acetaminophen is an important OTC analgesic given its demonstrated lack of potential for causing GI or other bleeding and no known risk of Reye's Syndrome in children. But it is also true that acetaminophen products, as currently labeled and used, are associated with rare reports of unintentional overdose that may lead to serious hepatotoxicity. The issue of hepatotoxicity in association with acetaminophen use is not new and this issue was discussed in the panel report published in 1977. The purpose of today’s meeting is to revisit this issue in the context of data on unintentional overdose and determine whether additional measures should be taken to further decrease the risk of these events. The committee, after reviewing the available information, will be asked to discuss factors and circumstances that may contribute to these adverse events and to help determine, as appropriate, additional risk management efforts.
Acetaminophen is currently available in numerous combination and single ingredient OTC products. Within each group of products, a variety of formulations are marketed. The FDA has oversight of the required labeling for OTC products but does not oversee their marketing and advertising. This responsibility lies with the Federal Trade Commission. Acetaminophen is also available in many prescription products. Currently, there are almost two hundred approved New Drug Applications (NDA) or abbreviated New Drug Applications (ANDA) for products that contain acetaminophen in combination with a narcotic analgesic. FDA regulates the labeling and advertising of these products; however, FDA does not regulate the practice of pharmacy, nor the type of information placed on the dispensing container by the pharmacist.
Points for Committee Discussion
a. Discuss possible factors or circumstances that may contribute to these events? Examples of possible factors could include, but are not limited to, the following:
4. Inadequate pain management with either OTC or prescription medications appears to be a factor for some individuals to take more than the recommended daily dose. The OTC products already have instructions regarding the maximum daily dose permitted. This, however, does not preclude individuals from either not reading or understanding these instructions or they ignore these instructions all together. The prescription products, dispensed by a pharmacy, may not include information on the maximum daily dose on the container although this information is available in most prescription labeling.
a. What measures should the agency consider to reinforce the message that exceeding the recommended dose can lead to toxicity for both OTC and prescription products?
For OTC products, possible measures could include but are not limited to the following:
For prescription products, possible measures could include but are not limited to the following: