Chantix and faulty adverse-event reporting

By Michael Cohen, president of the Institute for Safe Medication Practices

Last week we published QuarterWatch, which tracks side effects reported to the Food and Drug Administration, for the third quarter of 2010. Of note, one drug that stood out was Chantix (varenicline), the stop-smoking drug that is heavily advertised on TV. Since 2009, Chantix has carried a boxed warning on its label about a possible association with suicidal thoughts and aggressive behavior.

Before the third quarter of 2010, FDA's adverse-event database had shown 37 suicides reported to the agency by Pfizer, and an additional 85 reported by consumers and doctors.

During that quarter, we found that hundreds of older serious psychiatric adverse-event reports regarding Chantix were not initially entered into the FDA Adverse Event Reporting System (AERS) by Pfizer. Most notable were 150 cases of completed suicides, some dating to 2007.

When a drug company learns of a patient's death, an "expedited" report is to be submitted to the FDA within 15 days. But for unknown reasons, Pfizer classified these suicides among less serious injuries and submitted them amid hundreds of other less serious reports as an appendix to a quarterly report. . . .

This meant that safety analysts were unaware of more than half of the reported suicide cases in which Chantix was the primary suspect drug, and did not have available hundreds of other reported cases of serious psychiatric side effects. . . .

In response to QuarterWatch, FDA acknowledged that the reports were initially sent in a way that did not allow for comprehensive evaluation. They also noted that a few other makers were also submitting some adverse-event reports through "improper" channels.

FDA said the reports about Chantix confirmed what they already knew about Chantix and would not have changed the agency's position on the drug's risks and benefits. FDA also initiated more post-market safety activities such as requiring Pfizer to conduct a large, comparative, post-market clinical trial assessing the safety of Chantix among other smoking cessation aids.

When we first examined varenicline data in 2008, reports for this drug outnumbered reports for all other U.S. prescription drugs, although prescriptions and reported events later declined. Now, with a spike of 1,055 serious events reported in the third quarter of 2010, varenicline again surpassed all other drugs we monitor and also ranked first in reported deaths, more than twice those of any other drug.

Two other drugs also presented safety signals during Q3 2010. The new diabetes drug Victoza was linked to reports of pancreatitis. FDA approval of this drug was controversial because of uncertainty about its cardiovascular risks, and because animal studies showed an increased risk of thyroid cancer. Early reports did not speak to these still unresolved issues, but did reveal a marked signal for pancreatitis. Evidence accumulates that similar drugs like Januvia and Byetta may all share an elevated risk of pancreatitis, although possibly to differing degrees.

Signals were also seen with Seroquel (quetiapine). The drug shares with other antipsychotic drugs the risk that some of its most common side effects can be irreversible, notably some cases of diabetes and certain movement disorders. In the third quarter of 2010 we noted hundreds of new reported cases of diabetes associated with quetiapine, together with a smaller number of reports of dyskinesia (involuntary muscle movements), dystonia (spasms or prolonged contractions), and parkinsonism (tremors or muscle rigidity).

Medicines usually provide much needed benefits to consumers when used safely. . . . But I highly recommend that you sign up for customized safety alerts for the drug you take at http://consumermedsafety.org/alerts.asp.