FDA Drops Boxed Warning From Chantix Label

Decision follows recommendation from agency advisors

The FDA has approved updates to the labeling for varenicline (Chantix, Pfizer), including removal of the boxed warning regarding serious neuropsychiatric events. The removal of the boxed warning was based on results from a pivotal smoking-cessation trial in patients with and without a history of psychiatric disorders, and was consistent with recent recommendations from the FDA’s Psychopharmacologic Drugs Advisory Committee and its Drug Safety and Risk Management Advisory Committee.

Additional labeling revisions based on the EAGLES trial include updates to the corresponding warning regarding neuropsychiatric safety and the addition of information on the superior efficacy of varenicline compared with bupropion or a transdermal nicotine patch.

The updated warning in the varenicline label notes that post-marketing reports of serious or clinically significant neuropsychiatric adverse events in patients treated with varenicline included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Patients attempting to quit smoking with varenicline should be observed for the occurrence of such symptoms and should be instructed to discontinue varenicline and contact a health care provider if they experience such symptoms.

The Evaluating Adverse Events in a GLobal Smoking CEssation Study (EAGLES) was a randomized, blinded, active- and placebo-controlled trial conducted by Pfizer in collaboration with GlaxoSmithKline at the request of and designed in consultation with the FDA. The study was the first to compare the safety and efficacy of varenicline with that of bupropion (Zyban, GlaxoSmithKline) and a nicotine replacement patch in smokers with and without a history of psychiatric disorders. Approximately 8,000 subjects participated in the study. The trial was designed to compare the risk of clinically significant neuropsychiatric adverse events in patients using varenicline, bupropion, nicotine replacement therapy, or placebo as a smoking-cessation aid during 12 weeks of treatment, and to determine whether smokers with a history of psychiatric disorders are at a greater risk for developing clinically significant adverse events compared with smokers without a history of psychiatric disorders.

In the study, varenicline was not associated with an increased incidence of clinically significant neuropsychiatric adverse events in a composite endpoint consisting of anxiety, depression, feeling abnormal, hostility, agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, and irritability in patients without a history of psychiatric disorders.

In the cohort of patients with a history of psychiatric disorders, more events were reported in each treatment group compared with the nonpsychiatric cohort, and the incidence of events in the composite endpoint was higher for each of the active treatments compared with placebo. Risk differences compared with placebo were 2.7% for varenicline; 2.2% for bupropion; and 0.4% for transdermal nicotine. Serious neuropsychiatric events were reported in 0.6% and 0.2% of varenicline- and placebo-treated patients, respectively, with 0.5% and 0.2% of these events involving psychiatric hospitalization.

Varenicline was approved by the FDA in May 2006 as a prescription medication that, along with support, can help adults (18 years of age and older) to stop smoking.

Source: Pfizer; December 19, 2016.