Expert Warned FDA about Chantix

Yesterday ABCnews.com reported that John Spangler, director of Tobacco Intervention Programs at the Wake Forest University School of Medicine, warned the FDA and Pfizer a year ago of safety concerns with Chantix (varenicline). His warning foreshadowed last month's report from the Institute for Safe Medication Practices (ISMP) showing a high level of adverse events associated with the drug.

In a May 2007 letter to the editor responding to a Pfizer-funded safety study on use of Chantix over a 12-month period, Spangler raised questions about the high rate of adverse events in the Chantix-treated patients, 25 percent of whom dropped out of the study due to an adverse event, as compared with 10 percent of the placebo group. Moreover, 6 percent of the patients on Chantix experienced an adverse event that was considered serious. The investigators give little detail about these events, except to note that many were "cardiovascular conditions known to be comorbid with cigarette smoking." Only 2.4 percent of the patients who were on placebo experienced a serious adverse event.

"In this situation in particular, we're talking serious adverse events -- cardiovascular events," Spangler is quoted by ABCnews. "If you're putting someone on a drug that causes cardiac effects -- especially if they're already at higher risk of such effects -- you're doing them harm. You then have to do a risk-benefit study to see if the harm is greater than the benefit."

In his letter, Dr. Spangler notes the small number of participants (251 Chantix, 126 placebo) in the trial and states that "[u]ntil further safety data are available, these [safety] concerns should be made broadly public and require a long-term randomized controlled clinical trial adequately powered to determine actual safety."

As noted in the ISMP report, there were also some cardiovascular events during the preapproval trials of Chantix. The FDA safety reviewer noted that "[t]he serious adverse event data suggest that varenicline may possibly increase the risk of cardiac events, both ischemic and arrhythmic, particularly over longer treatment periods," although the reviewer, Howard Josefberg, M.D., noted that this finding was "far from definitive."

The experience with Chantix points out the need for the FDA to pay close attention to safety signals and, when appropriate, to require drug companies to conduct large clinical trials that can provide more definitive data on safety. In the meantime, smokers should be informed of the potential risks associated with Chantix.

-- PM