FDA Says Not Enough Evidence to Drop Chantix Warning

Federal regulators say Pfizer has provided low-quality evidence to support its request to remove a bold-letter warning from its anti-smoking drug Chantix about suicidal behavior.

The twice-a-day tablet has carried the Food and Drug Administration’s strongest warning label, known as a black box, since 2009 following reports of suicidality, hostility and depression among some patients. But the New York drugmaker has asked the FDA to drop the boxed warning, pointing to recent studies and analyses suggesting there is no difference in psychiatric problems between people taking Chantix and other smoking-cessation aids.

The FDA will put the issue to a panel of outside experts on Thursday. But in briefing documents posted online Tuesday, the agency notes that there is little precedent for removing such a warning from a prescription drug.

Further, staff scientists say they have “concerns about the validity” of data submitted by Pfizer, including five company-sponsored studies that measured suicidal tendencies based on a questionnaire. Other large studies conducted by outside groups also provided “evidence of insufficient quality to either rule in or rule out increased risk of suicide.”

FDA scientists note that Pfizer was previously required to conduct a large, comprehensive study of psychiatric side effects between patients taking Chantix versus another popular anti-smoking medication, bupropion. Those results, which are expected to be completed in about a year, should be considered as part of any decision to remove the drug’s black box, the agency reviewers write. Despite that opinion, FDA will ask a panel of psychiatric and drug safety experts to vote on whether to remove the boxed label. The agency is not required to follow the recommendations of its panels.

Chantix’s safety has been debated in medical journals and courtrooms since 2007, when reports of suicide, agitation and other problems first began streaming into the FDA. The agency notes that such reports have continued to date, with 105 adverse event reports about psychiatric problems with Chantix submitted to the FDA between January 2013 and June 2014.

New York-based Pfizer has paid roughly $300 million to settle more than 2,500 lawsuits alleging that Chantix caused various psychiatric problems, injuries and suicides.

Last week, five public safety advocacy groups told the FDA that the bolded warning language should actually be expanded to include information about blackouts, convulsions and other problems reported in some patients.

The drug’s labeling currently tells patients to stop taking Chantix immediately if they experience agitation, depressed mood, suicidal thinking and other behavioral changes. Doctors are advised to weigh the drug’s risks against its potential benefit of helping patients quit smoking.

Pfizer’s drug works by binding to the same spots in the brain that are activated by nicotine when people smoke. The drug, known generically as varenicline, blocks nicotine from binding to those spots and prevents the release of “feel-good” brain chemicals that make smoking so addictive.

Chantix had global sales of $648 million last year. That was down about 26 percent from the drug’s peak sales of $883 million in 2007.