FDA: Keep boxed warning on Chantix

October 21, 2014

An FDA advisory committee has voted to keep the boxed warning for varenicline (Chantix, Pfizer) that states that the drug may cause serious neuropsychiatric events.

An FDA advisory committee has voted to keep the boxed warning for varenicline (Chantix,Pfizer) that states that the drug may cause serious neuropsychiatric events.

Varenicline is a prescription medication used to help adults quit smoking. It is a non-nicotine medication that acts as a nicotinic receptor partial agonist that blocks nicotine from binding its receptors in the brain.

Varenicline’s drug label currently contains a boxed warning for serious neuropsychiatric events and contains the statement: “Advise patients and caregivers that the patient should stop taking Chantix and contact a healthcare provider immediately if agitation, hostility, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior while taking Chantix or shortly after discontinuing Chantix.

The manufacturer of varenicline, Pfizer, has asked the FDA for permission to remove the boxed warning about suicidality, behavior changes and other psychiatric risks from the drug’s label. Pfizer made its case to the FDA’s Psychopharmacology Drugs Advisory Committee and its Drug Safety and Risk Management panel. The company cited research from five observational studies which suggests that there is no or minimal psychiatric risk attributable to the drug. The studies reported neuropsychiatric medical encounters, completed suicides, nonfatal self-harming events and/or initiation of antidepressant treatment. In two meta-analyses of the clinical trial data, no increased risk of these events associated with varenicline was shown.

Pfizer executive Christopher Wohlberg, MD, PhD, told the panel that studies had confirmed that varenicline is "the single most effective smoking cessation aid" now available, and that the warning was unnecessarily inhibiting patient access. He said research had shown that boxed warnings do have "a significant impact" on prescribing.

FDA staff disagreed with Pfizer on most of their points and cited several limitations in the observational data and meta-analyses as well as Pfizer’s interpretation of the adverse event reports. Nearly all members of the FDA staff agreed that the data submitted by Pfizer was too limited to justify weakening the warning. Eleven of the 18 voting members voted to keep the boxed warning, and 6 members said that the warning should be strengthened.

A prospective trial, specifically designed to evaluate varenicline’s psychiatric risks is now underway and will be completed in 2015.

Erin Bastick is a PharmD Candidate 2016, Ohio Northern University, Ada, Ohio, and an inpatient intern at University Hospitals, Cleveland.