OTC ANALGESIC/ALCOHOL WARNING LEFT TO FDA's DISCRETION

OTC ANALGESIC/ALCOHOL WARNING LEFT TO FDA's DISCRETION after the Nonprescription Drugs and Arthritis Advisory Committees could not reach a consensus on the kind of warning that should be required. The joint committee voted on Sept. 8 to place a warning for heavy drinkers on labels of OTC aspirin, ibuprofen, and naproxen products. Because the committee could not reach a consensus on various elements of the label -- including how specific the warning should be and whether to recommend physician consultation -- FDA Office of OTC Drug Evaluation Director Michael Weintraub, MD, said the agency would consider the committee members' diverse comments in devising a label warning. Earlier in the meeting, the committee voted 9-1 (with two abstentions) for a warning label that specifically cited G-I bleeding risks. However, several committee members later expressed confusion about the nature of the vote. Some members advocated placing the G-1 bleeding warning as a clause in a larger, generalized warning about the danger of alcohol interaction with OTC analgesics, while others supported drug-specific warnings. The joint committee did agree that the level of alcohol consumption in the warning should remain vague. Earlier in the meeting, the joint committee was asked to consider a range of warning statements targeting people who drank "excessively," "daily" or "more than three drinks" per day. Arthritis Committee member Mary Moore, MD, Einstein-Moss Arthritis Center, suggested that such terms were open to consumer misinterpretation. "You can drink excessively every weekend and still be in trouble," Moore maintained. "So in terms of specificity, I would want the warning about alcohol to be very general," she urged. "I don't think we know enough [about alcohol consumption] to make it specific." In a presentation on various labeling approaches, FDA Marketing Practices and Communication Branch Director Louis Morris, PhD, argued for a short, specific and direct warning to the consumer regarding possible risks of concomitant analgesic and alcohol use. In addition, he recommended including a set number of drinks in the label as a cut-off figure because many heavy drinkers may not think of themselves as such. He also recommended that the hazard being warned against should be described to provide the consumer with "motivation" to avoid it. Nevertheless, Morris observed that whatever approach the committee decided on would represent a "trade-off." While a specific warning better educates consumers, it can also lead them to think that "they knew everything they needed to know about the medicine," according to Morris. "We want them to have some uncertainty, and not feel overconfident, [so they will] ask their doctor." Arthritis Committee member George Ehrlich, MD, University of Pennsylvania, suggested that an "ask your doctor" statement would have the added advantage of scaring some consumers away from using analgesics with alcohol. Ehrlich also supported a universal alcohol warning for all OTC analgesic ingredients. "We are not yet aware of the consequences of label changes," Ehrlich said. "With labeling, you're driving people in this direction, or that direction." Instead, "what you're really trying to do is inform people that taking medicine isn't always safe, and that they should be aware that . . . certain predictable events can arise from taking medicine," Ehrlich remarked. He asserted that "whether these problems are in the gut or the liver or in [other organs] is to some extent, in an over-the-counter medication, irrelevant." Ehrlich also questioned the committee's recommendation to require an alcohol warning for liver toxicity associated with acetaminophen. Weintraub responded that, in light of the class labeling discussion, the agency would reconsider the phrasing of the warning. Several committee members objected to the idea of a class-wide label linking the risks of aspirin, ibuprofen and acetaminophen. "If we want the label to reach individuals, it seems to me misleading to say that the adverse effects of aspirin are the same as acetaminophen, because they are different compounds," Marcus Reidenberg, MD, Cornell Medical Center, said. Citing his resistance to an ibuprofen/alcohol warning, Reidenberg acknowledged that "philosophically, I like the idea of class labeling, but I don't see the data here to support it." Nonprescription Drugs Advisory Committee Chairman Randy Juhl, PhD, University of Pittsburgh, maintained that "there is a precedent" for a class label warning "in that the [indication] labels now for the analgesics are all the same." He said that "the concern was that if one product had something and the other didn't, that we are subjected to bombardments" of criticism. "What is the advantage of telling people that they can get stomach lesions or [something else]? Why don't we just tell them what you get with one [drug] and what you get with the other?" Louis Cantilena, MD/PhD, Uniformed Services, asked the committee. "If we try to inform people out there -- for whatever reason -- we can't camouflage the science." Reidenberg also suggested that the committee use the professional labeling outlining the drug interaction risks as a guide in developing the committee's recommended warning. "If it's in the professional labeling, then when we're reviewing an OTC drug, where the decision is often made by the patient and not by a professional, then is there any reason to not have it in the consumers" label as well?" Reidenberg asked.