The smoking-cessation drug has generated headlines overlinks to suicide, but the Pfizer pill is now being tied to other serious adverse events reported to the FDA, according to a study published in Drug & Therapeutics Bulletin. And the authors urge the FDA and Pfizer to conduct epidemiological studies to assess further risks and to issue new warnings. Wall Street, meanwhile, is worried the study will cause Chantix sales to go up in smoke.
Chantix is suspected of causing a "wide spectrum of injuries," including serious accidents and falls, potentially lethal cardiac rhythm disturbances, severe skin reactions, acute myocardial infarction, seizures, diabetess, psychosis, aggression and suicide, the authors write. The findings prompted the Federal Aviation Adminstration to ban pilots and air traffic controllers from using the drug.
In last year's fourth quarter, Chantix accounted for 988 serious injuries in the US reported to the FDA, more than any other individual drug in this time period. By comparison, the FDA received a median of five reports of serious injury for 769 different drugs. Only 35 drugs accounted for 100 or more reports, according to the study, which was conducted by the Institute for Safe Medication Practices.
The FDA recently issued a Public Health Advisory noting suicidal ideation, and attempted and completed suicide, but there were no numbers of reported psychiatric events among treated smokers, the authors note. From May 2006 through December 2007, the FDA received 227 reports of suicidal acts, thoughts or behaviors, 397 cases of possible psychosis and 525 reports of hostility or aggression. These included 28 cases of suicide and 41 mentions of homicidal ideation, 60 cases of paranoia and 55 cases of hallucination. The categories weren't mutually exclusive.
However, the adverse event reports describe other kinds of serious harm for which no warnings now exist, either from the FDA or Pfizer. These include accidents and injuries; vision disturbance; heart rhythm disturbances; seizures and abnormal muscle spasms or movements; moderate to severe skin reactions and diabetes, according to the authors. (Here is the summary).
"We have immediate safety concerns (about people taking Chantix while) operating aircraft, trains, buses and other vehicles, or in other settings where a lapse in alertness or motor control could lead to massive, serious injury." They also cite nuclear power reactors, high-rise construction cranes or life-sustaining medical devices.
"The extent to which Chantix has already contributed to accidental death and injury has not yet been investigated because these adverse effects had not been previously reported," they write. "We urge the FDA and the manufacturer to provide warnings to doctors and patients for those adverse effects that can be adequately documented through existing data, and to undertake on a priority basis epidemiological studies or other research to assess other potential risks."
A Pfizer spokesman sends us this statement: "We closely monitor post-marketing reports of adverse events that we receive for our medicines as part of our commitment to accurately reflect each product’s efficacy and safety profile in labeling. Pfizer reports all such events to the FDA and other regulatory agencies and communicates safety information to physicians and patients in a variety of ways including through labeling and educational materials.
"Based on Pfizer and the FDA’s continuous review of all available safety information, including adverse event reports received to date, the current Chantix label accurately reflects the product’s efficacy and safety profile. For example, the current label includes safety information pertaining to certain serious neuropsychiatric symptoms, as well as driving and operating machinery.
"We understand that the Institute for Safe Medication Practices report was based solely on a review of post-marketing adverse event reporting data. It is important to understand the limitations of spontaneous adverse event reporting. Often these reports lack sufficient medical information and/or have confounding factors that prevent a meaningful assessment of causality."
Meanwhile, Sid Wolfe of Public Citizen also issued a statement saying the large number of adverse reactions "adds new urgency to our previous safety concerns about Chantix. It also highlights the dangerous inadequacy of the response of Pfizer and the FDA to the rapidly increasing number of serious, life-threatening adverse events seen with this drug."
He goes on to reiterate concerns he expressed last year in which he cited an "inadequate amount of information" about psychiatric adverse events that occurred in the randomized trials preceding Chantix approval. In one of the studies, 6.8 percent of patients using Chantix had psychiatric adverse events as opposed to only 2.4 percent of those given a placebo, Wolfe says.
The study prompted Tim Anderson, an analyst at Sanford Bernstein, to issue this note: "In the current safety-conscious environment, where will this lead to next? With the recently updated Chantix label (includes a bolded warning, but not a Black Box warning) it is unclear whether additional regulatory action will be taken.
"What is clearer, however, is that consensus forecasts for Chantix appear to be too high given current prescription trends. The most recent weekly prescription figures show that new prescriptions for Chantix are declining by nearly 30 percent year-over-year. This compares to consensus forecasts that have Chantix growing in 2008 and beyond. On the current trajectory, consensus sales forecasts for Chantix could be too high by as much as $500 million to $1 billion by 2012.
"Our estimates have been too high as well – given prescription trends we are lowering our sales forecasts for the product. Our 2008 worldwide Chantix sales forecast drops from $1.14 billion to $909 million; our 2012 forecast drops from $1.65 billion to $720 million."