Pfizer's Chantix (varenicline), already under fire for safety issues, was targeted again late last week when the Institute for Safe Medication Practices, a nonprofit best known for its work in preventing medication errors, reported that the smoking cessation product was associated with more serious adverse event (SAE) reports than any other drug.
The report looked at US adverse event reports received by FDA in the fourth quarter of 2007. During that period, only 35 drugs accounted for 100 or more SAE reports. (FDA received reports on 769 drugs in the period; the median number of SAE reports per drug was five.)
Chantix logged 998 reports, followed by interferon beta (640), etanercept (555), infliximab (554), fentanyl (404), and oxycodone (372).
The list of events Chantix has been associated with since launch is strikingly diverse, including hyperglycemia/new-onset diabetes, convulsions, embolic and thrombotic events, hostility/aggression, psychosis, and vision disturbance. In all, there were 78 deaths, including 28 suicides, in which varenicline was suspected of playing a role.
The good and bad features of the data, according to ISMP:
On the plus side: "Because of the large numbers of patients exposed to the drug, these data are capable of detecting events that might not show clearly in relatively small, relatively short clinical trials. A large share of these reports were investigated and submitted by the drug manufacturer, presumably with consistent procedures, and potential events were selected using criteria that had previously undergone validation testing. In addition, these events occurred under real world conditions, and not the narrowly selected patient population in the clinical trials."
On the minus side: "[T]hese reports do not establish causality; most patients were taking multiple drugs; the event classification tool is limited to identifying potential cases, and is not definitive. Reporting is voluntary for consumers and health professionals, and little is known about reporting rates. Crude published estimates show that from 1 percent to 10 percent of all serious events are reported, but with wide variation among drugs, event times and over time."
What's more, the study's authors point out that it is possible that the number of reports was artificially boosted by adverse publicity surrounding Chantix or some other non-medical cause.
The challenge in sorting out Chantix's effects is that a number of the events might be accounted for, in part, by nicotine withdrawal. Nicotine, of course, has been linked in various ways with depression, schizophrenia, ADHD, and other psychiatric maladies, and it is thought that many potential patients use tobacco as a form of self-medication to help control their symptoms. These kinds of patients, as well as patients with recent cardiac disease and those taking a wide variety of drugs, were excluded from Pfizer's Phase III trials.
"We have concern about the use of varenicline by persons in settings where the risk of accident is high," the study concludes. "We recommend doctors and patients exercise caution in the use of varenicline, and consider alternative methods of smoking cessation. The FDA and the manufacturer should on a priority basis assess the information available and conduct additional research where current data are insufficient to resolve questions about the safety of varenicline."