1 Boring Old Man

Smoke This: Pfizer Wants Serious Warnings Removed From Chantix

Pharmalot: WSJ

By Ed Silverman

September 24, 2014

In a boost to Pfizer, the FDA has updated labeling on its Chantix smoking-cessation pill to indicate the drug may not carry the risks of suicidal behavior, a controversial issue that prompted the agency to include a serious warning in the labeling in 2009. The changes are being made to reflect the results of various studies. One study involved a so-called meta-analysis of five studies involving nearly 2,000 patients that Pfizer says did not show an increase in suicide thoughts or actions among people who took Chantix compared with a placebo.

The drug maker also pointed to four observational studies of between 10,000 and 30,000 people that did not find differences in risk between Chantix and other nicotine treatments, although these had several limitations [most of the label changes appear on page 3]. The labeling change is welcome news for Pfizer, which hoped Chantix would become a blockbuster but has instead encountered a marketing challenge. Shortly after Chantix was approved in 2006, the drug was increasingly linked in news reports of acts of violence or suicide. The FDA issued successive alerts, the Federal Aviation Administration banned usage by pilots and air traffic controllers, and the Departments of Defense and Transportation restricted use in sensitive occupations. Meanwhile, Chantix sales slid to $648 million last year from $846 million in 2008. And Pfizer settled hundreds of lawsuits last year by people who claim Chantix caused them harm.

The labeling change, by the way, was made on September 19, but Pfizer had not publicly discussed the changes until today, when a watchdog group called the Institute for Safe Medicine Practices planned to release an analysis placing Chantix in an unflattering light and calling for the Black Box warning to be strengthened. The timing of the disclosure of the labeling change suggests that Pfizer sought to mitigate any negative publicity that may have ensued…

Pfizer would like the serious warning, which is known as a Black Box in regulatory parlance, removed, the Associated Press writes. A Pfizer spokesman writes us that the labeling change and upcoming meeting “both serve as a step forward in the process of accurately communicating the clinical and observational data” in relation to serious side effects referenced in the warnings section of the labeling.

Even though the Black Box remains unchanged, Pfizer may benefit to some degree, anyway. How so? The updated labeling now includes new information about the studies in the Warnings & Precaution section. As a practical matter, the Black Box is still front and center, but new language may soften the blow, at least if enough physicians interpret the new information as Pfizer would like. We asked the FDA if the Black Box may be removed and will update you with any reply.

[UPDATE: Thomas Moore, a senior scientist at ISMP, contends the labeling may not help Pfizer very much. "The new studies added to the label provide little new insight into the psychiatric side effects of Chantix. The meta-analysis of suicidal behaviors included only a few of the many clinical studies, was much too small to detect these rare but catastrophic events, and was not published or peer reviewed.  The observational studies had even more limitations. Neither the observational studies nor the meta analysis included the full range of psychiatric side effects reported."]

Meanwhile, ISMP reviewed side effect reports filed with FDA and found that Chantix accounted for more cases of suicide, self-injury or homicidal thoughts than any other therapeutic drug between 2007 and the third quarter of 2013. Moreover, Chantix ranked first in both suicidal and self-injurious thoughts as well as homicidal thoughts, and these reports outnumbered those for any other drug by more than three times. Moore says there is still more evidence that Chantix causes psychiatric side effects. And so the watchdog group plans to ask the FDA to further strengthen the Black Box warning and widen the restrictions on Chantix use to still other occupations. He declined to name those occupations…

There were limitations on some Pfizer findings, as well. The observational studies were conducted after widespread publicity about Chantix and suicidal or hostile behavior, which means patients with a history of psychiatric illness may have been prescribed an alternative treatment. And only reports that resulted in hospitalizations were included, suggesting other incidents were not noted. 

[UPDATE: ISMP’s Moore writes us that "the study of psychiatric hospitalizations omitted 85% of the known psychiatric side effects and depended on diagnostic codes that had not been studied or validated."]

[EDITOR’S NOTE: An earlier version of this story indicated all the observational studies were conducted by Pfizer].

I declare ongoing resentments against Pfizer on any number of grounds: the way Zoloft® was approved by the FDA was insider trading [see [zoloft: the approval III…]; their shameful clinical trial of Zoloft® in adolescents [Wagner et al][see tuning the quartet…]; financing Robert Gibbons’ recurrent attacks on the various Black Box Warnings [see very monotonous…]; promoting Gabapentin [Neurontin®] as a pain medication [E-mails suggest Pfizer tried to suppress study on drug]; but mostly for their ads that put the phrase "chemical imbalance" into the public register.

The labeling change, by the way, was made on September 19, but Pfizer had not publicly discussed the changes until today, when a watchdog group called the Institute for Safe Medicine Practices planned to release an analysis placing Chantix in an unflattering light and calling for the Black Box warning to be strengthened. The timing of the disclosure of the labeling change suggests that Pfizer sought to mitigate any negative publicity that may have ensued…