Chantix (varenicline), thoughts of suicide/self-injury and homicide

FDA is moving the smoking cessation drug Chantix into the drug safety spotlight tomorrow.

by Michael R. Cohen, R.Ph.

Published Oct. 15, 2014, 11:41 a.m. ET

FDA is moving the smoking cessation drug Chantix into the drug safety spotlight tomorrow. The agency has scheduled a joint public meeting of two advisory committees to review the current Boxed Warning and Medication Guide.

Some history: In 2008, my organization, the Institute for Safe Medication Practices (ISMP) commented on an unexpectedly large number of serious psychiatric and other ADEs for this drug. Specifically, we expressed concern about thoughts (ideation) of suicide, self-injury, or homicide. Also, in addition to these risks, Chantix has been associated with sudden blackouts, seizures, and impaired vision. We thought it was troubling that an alternative to nicotine replacement products (gum, patch, etc.) was the primary suspect in more reported cases of serious injury than toxic chemotherapeutic agents, potent opioids, or powerful immunosuppressant drugs.

In response, the Federal Aviation Administration banned the use of Chantix by airline pilots, the Department of Transportation limited its use among truck drivers, and the Department of Defense prohibited its use by aircraft and missile crews. Also, several thousand patients have sued Pfizer, the manufacturer, related to the drug's psychiatric adverse effects, and thousands were compensated. The FDA required the company to add a Boxed Warning to the package insert and to provide more information in the Medication Guide in 2009. Some of this wording must now accompany print and TV ads, as you've no doubt seen and heard.

But now Pfizer is asking FDA to remove the boxed warning, citing studies that indicate that the drug is not a risk for suicide and aggressive behavior. Last month FDA revised the label to include these studies but the boxed warning remains.

In light of the meeting tomorrow, last month we reassessed selected Chantix adverse event data collected since drug approval 7 years ago, using as endpoints thoughts of suicide, self-injury, or homicide. These new data show that Chantix continues to account for more cases of suicidal, self-injurious, or homicidal thoughts than any other therapeutic drug from 2007 through 2013 — more than 3 times as many as the second-ranked drug. Chantix stands out even more prominently in the subset of homicidal ideation, with a 5-fold margin over the second-ranked drug, Seroquel. In addition to these risks, Chantix is also associated with sudden blackouts, seizures, and impaired vision.

We published these results recently in our QuarterWatch publication on September 25th. Then, last week, ISMP was joined by five leading nonprofit consumer, research, and medical organizations (Consumer Reports, Institute for Safe Medication Practices, National Center for Health Research, National Physicians Alliance, and Public Citizen) in filing a Citizen Petition with the FDA. The Citizen Petition documents the extensive scientific evidence that has expanded our understanding of the substantial risks of this smoking cessation drug. Appropriate warnings and careful monitoring can prevent many of these potentially catastrophic adverse drug events. The groups not only want to see the boxed warning retained, but they also want it to clarify and strengthen the Boxed Warnings about psychiatric side effects and have FDA place restrictions against Chantix use in sensitive and hazardous occupations. ISMP and the National Center for Health Research will testify at the meeting tomorrow.

We learned this morning that FDA is apparently recommending for now not removing the most serious warnings about the risk of psychiatric side effects. According to the Wall Street Journal report, FDA must have reached the same conclusions that we did in our Citizen Petition: that the studies Pfizer wanted added to the label had "design limitations" and the "limitations may underestimate the actual incidence of neuropsychiatric adverse events, and restrict ability to predict the direction of the relative risk." It will be interesting to see if the FDA panel tomorrow draws the same conclusions.