Acetaminophen Toxicity Headed To NDAC, New FDA Drug Safety Group

Potential liver toxicity risks from acetaminophen use are likely to be among the topics at the inaugural meeting of FDA's Drug Safety & Risk Management Subcommittee.

FDA's new safety subcommittee of the Pharmaceutical Science Advisory Committee is scheduled to hold its first meetings April 22-23.

Although the official agendas have not yet been released by FDA, tentative plans call for the first day to focus on acetaminophen safety and risks as part of a joint session with the Nonprescription Drugs Advisory Committee. NDAC has a two-day meeting scheduled for the same days (¹ 'The Tan Sheet' Jan. 7, 2002, In Brief).

[Editor's note: To sign up for webcasts of the April 22-23 meetings, visit ² www.FDAAdvisoryCommittee.com , a new Web site from the publisher of "The Tan Sheet."]

The acetaminophen hepatotoxicity issue is the type of long-standing safety and risk management topic that appears ripe for the agency's new safety subcommittee.

FDA officials have been concerned recently that the alcohol warnings on acetaminophen, developed over the last decade, may not be sufficient as a deterrent to misuse. NDAC first recommended a warning for acetaminophen at a June 1993 meeting. Later that year, the committee expanded its advice to include alcohol warnings for aspirin, ibuprofen and naproxen sodium.

The agency followed the advisory committee's recommendation by issuing a proposed rule in November 1997 requiring analgesics to carry different versions of an alcohol warning. The final rule, published in October 1998, mandates that labeling for acetaminophen products state: "If you consume three or more alcoholic drinks every day, ask your doctor whether you should take acetaminophen or other pain relievers/fever reducers. Acetaminophen may cause liver damage" (³ (Also see "Analgesics Alcohol Warning Required By April 23 In Final Rule" - Pink Sheet, 26 Oct, 1998.), p. 3).

However, at a meeting last February, a top FDA official charged with postmarketing assessment - Peter Honig, MD - recommended increased intervention to forestall more frequent use of the analgesic to commit suicide (⁴ (Also see "OTC Acetaminophen Access Limitations To Be Considered By FDA" - Pink Sheet, 19 Feb, 2001.), p. 3).

Honig's comments indicate one line of discussion for the proposed April 22 review. The committees could be asked to discuss whether packaging (such as blister packs) or size limitations could be helpful in reducing the risk of acetaminophen misuse.

The drug safety subcommittee was formed as part of FDA's efforts to upgrade its risk management decision-making (⁵ (Also see "Drug Risk Management Advisory Panel To Be Formed Under Pharm. Science" - Pink Sheet, 19 Nov, 2001.), p. 12). The agency also is seeking to increase funding for postmarketing surveillance activities through reauthorization of the Prescription Drug User Fee Act.

The new subcommittee has several members with experience in recent OTC issues. Duke University Associate Professor of Psychology Ruth Day, for example, spoke in favor of using pictograms in OTC labeling at a recent meeting on the dangers of sedating OTC drugs.

Another subcommittee member, University of Pennsy-lvania Center of Clinical Epidemiology & Biostatistics Director Brian Strom, addressed the techniques used in a study of OTC antihistamine safety in an editorial in the March 7, 2000 Annals of Internal Medicine.

Commenting on a study that found Benadryl impairs drivers more than alcohol, Strom was critical of the techniques used to measure the relative effects of various antihistamines and alcohol (⁶ (Also see "Benadryl Driving Impairment Study Findings "Suspect" - W-L" - Pink Sheet, 13 Mar, 2000.), p. 8).

Strom also has addressed the safety of acetaminophen in a past editorial. In an article in the July 26, 1995 Journal of the American Medical Association, Strom referred to acetaminophen as the "lowest risk" analgesic.

The NDAC meetings will mark the beginning of the tenure of Uniformed Services University of the Health Sciences' Louis Cantilena, MD/PhD, as committee chair. Cantilena has served multiple terms on NDAC and headed a July 2000 meeting on labeling for the Today Sponge.

With a dearth of recent Rx-to-OTC switch issues, NDAC instead may increasingly be asked by FDA to look at other types of regulatory issues, such as the planned acetaminophen evaluation.

An acetaminophen review in April could negatively affect the OTC industry's standing with consumers. Industry recently faced a public relations setback resulting from the withdrawal of phenylpropanolamine from the market.