FDA Health Advisory Recommends Limited Prescribing for COX-2 Inhibitors
FDA on Dec. 23, 2004, issued a health advisory recommending that doctors carefully consider a patient's risk of cardiac disease before prescribing Pfizer's COX-2 inhibitors Celebrex and Bextra, after several "conflicting studies" raised questions about the painkillers' cardiovascular risks, the Baltimore Sun reports (Bor/Kohn, Baltimore Sun, 12/24/04).
FDA also announced that it will broaden its review of COX-2 inhibitors to include all "preventive studies" -- which involve healthy patients with a disposition to certain illnesses to determine whether the drugs being studied could prevent those illnesses. The findings of a preventive study prompted the agency's earlier warnings about Celebrex and naproxen, an over-the-counter painkiller sold by Bayer under the name Aleve.
The advisory comes after the recent withdrawal of Merck's COX-2 inhibitor Vioxx, and news of studies questioning the cardiovascular safety of Bextra and Celebrex (Getter, Los Angeles Times, 12/24/04).
The advisory did not ban prescriptions of either drug and noted that patients who were at high risk of gastrointestinal bleeding or had not responded to other painkillers "may be appropriate candidates" for the drugs (Harris/Berenson, New York Times, 12/24/04). The advisory also recommended patients who take nonsteroidal anti-inflammatory drugs -- including naproxen, ibuprofen or aspirin -- strictly adhere to the label directions and not take the medication for more than 10 consecutive days without first consulting with a doctor (Rubin, USA Today, 12/27/04).
The COX-2 inhibitor advisory is "less forceful" than one issued by British regulators earlier in the week advising physicians to switch patients with heart disease to different drugs "as soon as is convenient," the New York Times reports (Harris/Berenson, New York Times, 12/24/04). FDA said the advisory is an interim step before a regulatory panel in February reviews all studies of COX-2 inhibitors. The agency also announced that it will expand the scope of the "much-anticipated" hearing to include over-the-counter NSAIDs such as Aleve, the Chicago Tribune reports (Japsen, Chicago Tribune, 12/24/04).
"The actions that we're recommending in the advisory are for more limited prescribing than would currently be included in the approved labeling for these products," John Jenkins, director of FDA's Office of New Drugs, said in a news briefing (Baltimore Sun, 12/24/04). Jenkins noted that there were conflicting studies about the cardiovascular risks of COX-2 inhibitors and said, "We think we need to take time to do a careful review" (Los Angeles Times, 12/24/04). Jenkins said the advisory "may well mean that (doctors) decide to use other agents instead of (Celebrex and Bextra) until we can sort out more clearly what the conflicting data show" (Pugh, Knight Ridder/Pittsburgh Post-Gazette, 12/24/04). He added that the advisory is "an interim measure, pending further review of data that continue to be collected" (USA Today, 12/27/04). No further action by FDA on COX-2 inhibitors is expected until the February hearing (Knight Ridder/Pittsburgh Post-Gazette, 12/24/04).
Pfizer spokesperson Susan Bro said in a statement that the February hearing "is the appropriate forum for a thorough review" of NSAIDs, adding, "The full study results must be shared with the medical, scientific and regulatory experts so that we have a more complete understanding of the risks and benefits of these medicines" (Chicago Tribune, 12/24/04). Marc Hochberg, head of rheumatology at the University of Maryland School of Medicine, said, "I think they're following their marching orders to recommend a safe, prudent approach to physicians" (Baltimore Sun, 12/24/04).
However, Sidney Wolfe, director of Public Citizen's Health Research Group, criticized FDA for "once again siding with a large pharmaceutical company, in this case Pfizer, in refusing to ban ... Celebrex and Bextra." Wolfe added that the COX-2 inhibitors "are doomed drugs that are in the twilight of their existence. Breathing extra life into them is surely beneficial to Pfizer executives and stockholders but is a step backward for an agency that is supposed to be a part of the public health service" (Chicago Tribune, 12/24/04).
FDA safety officer David Graham, who criticized the agency's handlings of Bextra and Celebrex at a recent congressional hearing, said the advisory did not go far enough and would probably not change the way people take the drugs. Graham said, "To assume that people will follow this is wishful thinking," adding, "The FDA is saying they can't be sure these drugs are safe. Well, if they're concerned, perhaps people shouldn't be using (the drugs) at all" (Baltimore Sun, 12/24/04). Ira Loss of Washington Analysis said, "The statements today are more political than they are scientific," adding, "The import of this meeting in February has grown, and they may need to act as a reassuring factor to get everybody away from the hysteria they are in at the moment" (Chicago Tribune, 12/24/04).
FDA said it will broaden its review of painkiller side effects to include NIH-sponsored studies on at least 18 anti-inflammatory drugs, as well as look at the side effect data in all preventive studies of Celebrex and Bextra.
"From a cardiovascular risk perspective, we're casting a very wide net," Jenkins said, adding, "We're definitely reviewing all the NSAIDs." Michael Ellman, a rheumatologist at the University of Chicago, said, "I suspect the FDA is under such pressure from Congress that they'll do anything right now. It may be that it will take them so long to do the study that by the time it comes out, we won't be worrying about it" (Burton et al., Wall Street Journal, 12/24/04).
In related news, New Jersey-based Merck said it is likely that Chair and CEO Raymond Gilmartin will testify by March in "some" of the dozens of Vioxx-related lawsuits filed against the company, the AP/Philadelphia Inquirer reports. Ted Mayer, an attorney for Merck, said Gilmartin will likely testify in some of the 240 personal-injury or product-liability lawsuits filed in New Jersey. Mayer said two law firms are looking to set limits on Gilmartin's depositions and coordinate them with related litigation around the country; a state Superior Court judge earlier this month issued an order requiring Gilmartin to answer questions regarding his knowledge of Vioxx's risks prior to its Sept. 30, 2004, withdrawal (Johnson, AP/Philadelphia Inquirer, 12/29/04). Gilmartin's deposition would occur in closed proceedings (Todd, Newark Star-Ledger, 12/28/04).
"We believe that, when we get a chance to tell our story in court, it'll be clear that Merck did the right thing in terms of its study of the drug and the actions it took," Mayer said (AP/Philadelphia Inquirer, 12/29/04). Wayne Eastman, who teaches law and ethics at Rutgers Business School, said, "Merck wants as much as possible for this not to become something that is personalized and highly visible. If you have your CEO out there identified with the litigation, it's no longer dry arguments about science and statistics. ... The plaintiffs want it to be seen as a drama of corporate misconduct" (Newark Star-Ledger, 12/28/04).
NPR's "All Things Considered" on Thursday reported on the FDA's ability to ensure the safety of medications in the wake of several drug recalls in 2004. The segment includes comments Graham; Dr. Paul Stolley, a former FDA consultant; and FDA Acting Commissioner Dr. Lester Crawford (Silberner, "All Things Considered," NPR, 12/30). The complete segment is available online in RealPlayer.This is part of the California Healthline Daily Edition, a summary of health policy coverage from major news organizations. Sign up for an email subscription.