By Ed Silverman // May 18th, 2011
Adverse event data from the third quarter of 2010 show the risks of serious psychiatric side effects of Chantix, the smoking-cessation drug, were previously underestimated because Pfizer apparently failed to correctly submit hundreds of these episodes to the FDA, according to an analysis by the Institute for Safe Medicine Practices, a non-profit that regulary reviews the FDA adverse event database.
Notably, the ISMP found 150 cases of completed suicides, some of which dated back to 2007, that were not reported promptly as suicides within 15 days as required. Instead, the drugmaker apparently coded the suicides as “expected adverse events” among 26,000 such events, and added these to a quarterly periodic report, which is how less important, non-serious side effects are sent to the FDA.
What ISMP calls a “breakdown in safety surveillance” meant that, until July 2010, FDA analysts were not aware of more than half of the reported suicide cases in which Chantix was the primary suspect. And the agency also did not have available hundreds of other reported cases of serious psychiatric side effects, including psychosis, depression, or attempted suicide.
Consequently, the non-profit says the FDA should investigate why Pfizer was reporting suicide deaths as “expected adverse events,” especially prior to 2009, when safety concerns were being reviewed by the FDA. ISMP adds that this is not the first time issues have been raised with Pfizer’s adverse event reporting. The agency last year sent Pfizer a warning letter for failing to meet regulatory deadlines for reporting serious side effects with many of its drugs, although Chantix was not among those listed (the report is available here).
This is only the latest difficulty for Pfizer and its Chantix pill. For the past four years, the drug has caused a stir after being associated with suicidal behavior and vivid dreams (see here and here). Consequently, the government banned the Pfizer drug for pilots and licenses wouldn’t be issued to truck drivers taking the med (see this). The FDA subsequently imposed a risk management program and Pfizer added warnings.
A Pfizer spokesman sends us this to explain why there was a sudden spike in reports in the third quarter of 2010: “Pfizer has complied fully with FDA requirements regarding adverse events reports it has received related to the use of Chantix. The company has reviewed and analyzed these reports, shared them with the FDA, and communicated with the FDA with respect to them. All post-marketing reports of adverse events are reviewed by Pfizer, and reported to regulators, including the FDA.
“During discussions with the FDA in December 2009 and January 2010 regarding voluntary implementation of periodic Individual Case Safety Report submissions in electronic format, the FDA requested that Pfizer use this new format to resubmit the ICSRs for our products, including Chantix. This new format was to facilitate entry of reports into the AERS database. As a result of this request, Chantix reports previously submitted from 2006-2009 were resubmitted in third quarter 2010, with the majority of these reports being resubmitted in July.”
ISMP, for its part, had begun examining Chantix adverse event reports in May 2008, after noticing these outnumbered reports for other meds, including opioids and chemotherapy agents, which are known to be toxic (read this). At the time, you may recall Pfizer explained that stronger warnings were not necessary, and it was not surprising to see psychiatric side effects among smokers, especially those who might be experiencing nicotine withdrawal.
More recently, though, a pair of studies have linked to Chantix to disturbing behavior. One study in PLoS One found an association with serious acts of violence, such as physical abuse, physical assault and homicide (read here). Another that was published in the Annals of Pharmacotherapy cited links to violent and aggressive thoughts and acts, and also identified some of the common characteristics among people using the pill and their subsequent behavior (see this).
Two of the authors of these studies, by the way, are also on the ISMP Quarter Watch staff that reviews the FDA adverse event reporting system. One of them, Thomas Moore, recently agreed to serve as a consulting expert in the civil litigation regarding Chantix. For that reason, Pfizer declined to respond to ISMP prior to the release of its report. In the past, ISMP says Pfizer regularly declined to comment, but did not offer any reason.
[UPDATE: On May 19, the FDA issued a statement; here is an excerpt: "In July 2010, Pfizer, at the request of FDA, resubmitted a large number of adverse event reports that were initially sent to the agency in a way that did not allow for comprehensive evaluation. Although this resubmission included thousands of reports of potential adverse events, these events were spread out over a number of years, and had been reported to the agency periodically in summary safety reports. These reports confirm what we already knew about Chantix and would not have changed the Agency's position on the drug's risks and benefits, given that the data in these reports were consistent with those that led to the 2009 labeling change. At this point, based on the data, FDA does not have any new safety concerns with Chantix, though those that have been established remain under active review" (read the complete statement here). END UPDATE]
Chantix lawsuits regularly make headlines. The latest was filed earlier this month by the children of a Pittsburgh man who killed his wife and himself in 2009 while taking the pill. According to the complaint, Sean Wain, 34, had been using Chantix for up to two weeks before he began experiencing side effects that allegedly prompted him to kill his wife and himself. The murder-suicide left behind four minor children (you can read the lawsuit here).
cig smoke thx to jo naylor on flickr